|
1
|
Chen Y, Xu J, Li P, Shi L, Zhang S, Guo Q, Yang Y. Advances in the use of local anesthetic extended-release systems in pain management. Drug Deliv 2024; 31:2296349. [PMID: 38130151 PMCID: PMC10763865 DOI: 10.1080/10717544.2023.2296349] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Accepted: 11/15/2023] [Indexed: 12/23/2023] Open
Abstract
Pain management remains among the most common and largely unmet clinical problems today. Local anesthetics play an indispensable role in pain management. The main limitation of traditional local anesthetics is the limited duration of a single injection. To address this problem, catheters are often placed or combined with other drugs in clinical practice to increase the time that local anesthetics act. However, this method does not meet the needs of clinical analgesics. Therefore, many researchers have worked to develop local anesthetic extended-release types that can be administered in a single dose. In recent years, drug extended-release systems have emerged dramatically due to their long duration and efficacy, providing more possibilities for the application of local anesthetics. This paper summarizes the types of local anesthetic drug delivery systems and their clinical applications, discusses them in the context of relevant studies on local anesthetics, and provides a summary and outlook on the development of local anesthetic extended-release agents.
Collapse
Affiliation(s)
- Yulu Chen
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Jingmei Xu
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Ping Li
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of Obstetrics, Xiangya Hospital, Central South University, Changsha, China
| | - Liyang Shi
- College of Biology, Hunan University, Changsha, China
| | - Sha Zhang
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
| | - Qulian Guo
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Yong Yang
- Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| |
Collapse
|
|
2
|
Ishitsuka Y, Irie T, Matsuo M. Cyclodextrins applied to the treatment of lysosomal storage disorders. Adv Drug Deliv Rev 2022; 191:114617. [PMID: 36356931 DOI: 10.1016/j.addr.2022.114617] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 09/14/2022] [Accepted: 11/02/2022] [Indexed: 11/09/2022]
Abstract
Cyclodextrin (CD), a cyclic oligosaccharide, is a pharmaceutical additive that improves the solubility of hydrophobic compounds. Recent research has focused on the potential active pharmaceutical abilities of CD. Lysosomal storage diseases are inherited metabolic diseases characterized by lysosomal dysfunction and abnormal lipid storage. Niemann-Pick disease type C (NPC) is caused by mutations in cholesterol transporter genes (NPC1, NPC2) and is characterized by cholesterol accumulation in lysosomes. A biocompatible cholesterol solubilizer 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was recently used in NPC patients for compassionate use and in clinical trials. HP-β-CD is an attractive drug candidate for NPC; however, its adverse effects, such as ototoxicity, should be solved. In this review, we discuss the current use of HP-β-CD in basic and clinical research and discuss alternative CD derivatives that may outperform HP-β-CD, which should be considered for clinical use. The potential of CD therapy for the treatment of other lysosomal storage diseases is also discussed.
Collapse
Affiliation(s)
- Yoichi Ishitsuka
- Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Tetsumi Irie
- Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Department of Pharmaceutical Packaging Technology, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan
| | - Muneaki Matsuo
- Department of Pediatrics, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga 849-8501, Japan
| |
Collapse
|
|
3
|
Mitusova K, Peltek OO, Karpov TE, Muslimov AR, Zyuzin MV, Timin AS. Overcoming the blood-brain barrier for the therapy of malignant brain tumor: current status and prospects of drug delivery approaches. J Nanobiotechnology 2022; 20:412. [PMID: 36109754 PMCID: PMC9479308 DOI: 10.1186/s12951-022-01610-7] [Citation(s) in RCA: 74] [Impact Index Per Article: 24.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Accepted: 08/18/2022] [Indexed: 01/06/2023] Open
Abstract
Besides the broad development of nanotechnological approaches for cancer diagnosis and therapy, currently, there is no significant progress in the treatment of different types of brain tumors. Therapeutic molecules crossing the blood-brain barrier (BBB) and reaching an appropriate targeting ability remain the key challenges. Many invasive and non-invasive methods, and various types of nanocarriers and their hybrids have been widely explored for brain tumor treatment. However, unfortunately, no crucial clinical translations were observed to date. In particular, chemotherapy and surgery remain the main methods for the therapy of brain tumors. Exploring the mechanisms of the BBB penetration in detail and investigating advanced drug delivery platforms are the key factors that could bring us closer to understanding the development of effective therapy against brain tumors. In this review, we discuss the most relevant aspects of the BBB penetration mechanisms, observing both invasive and non-invasive methods of drug delivery. We also review the recent progress in the development of functional drug delivery platforms, from viruses to cell-based vehicles, for brain tumor therapy. The destructive potential of chemotherapeutic drugs delivered to the brain tumor is also considered. This review then summarizes the existing challenges and future prospects in the use of drug delivery platforms for the treatment of brain tumors.
Collapse
Affiliation(s)
- Ksenia Mitusova
- Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg, 195251, Russian Federation
| | - Oleksii O Peltek
- School of Physics and Engineering, ITMO University, Lomonosova 9, St. Petersburg, 191002, Russian Federation
| | - Timofey E Karpov
- Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg, 195251, Russian Federation
| | - Albert R Muslimov
- Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg, 195251, Russian Federation
- Sirius University of Science and Technology, Olympic Ave 1, Sirius, 354340, Russian Federation
| | - Mikhail V Zyuzin
- School of Physics and Engineering, ITMO University, Lomonosova 9, St. Petersburg, 191002, Russian Federation
| | - Alexander S Timin
- Peter The Great St. Petersburg Polytechnic University, Polytechnicheskaya 29, St. Petersburg, 195251, Russian Federation.
- School of Physics and Engineering, ITMO University, Lomonosova 9, St. Petersburg, 191002, Russian Federation.
| |
Collapse
|
|
4
|
Orientation of nanocarriers in subarachnoid space: A tweak in strategic transport for effective CNS delivery. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.103641] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
|
|
5
|
Fowler MJ, Cotter JD, Knight BE, Sevick-Muraca EM, Sandberg DI, Sirianni RW. Intrathecal drug delivery in the era of nanomedicine. Adv Drug Deliv Rev 2020; 165-166:77-95. [PMID: 32142739 DOI: 10.1016/j.addr.2020.02.006] [Citation(s) in RCA: 99] [Impact Index Per Article: 19.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 12/17/2019] [Accepted: 02/28/2020] [Indexed: 12/23/2022]
Abstract
Administration of substances directly into the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord is one approach that can circumvent the blood-brain barrier to enable drug delivery to the central nervous system (CNS). However, molecules that have been administered by intrathecal injection, which includes intraventricular, intracisternal, or lumbar locations, encounter new barriers within the subarachnoid space. These barriers include relatively high rates of turnover as CSF clears and potentially inadequate delivery to tissue or cellular targets. Nanomedicine could offer a solution. In contrast to the fate of freely administered drugs, nanomedicine systems can navigate the subarachnoid space to sustain delivery of therapeutic molecules, genes, and imaging agents within the CNS. Some evidence suggests that certain nanomedicine agents can reach the parenchyma following intrathecal administration. Here, we will address the preclinical and clinical use of intrathecal nanomedicine, including nanoparticles, microparticles, dendrimers, micelles, liposomes, polyplexes, and other colloidalal materials that function to alter the distribution of molecules in tissue. Our review forms a foundational understanding of drug delivery to the CSF that can be built upon to better engineer nanomedicine for intrathecal treatment of disease.
Collapse
Affiliation(s)
- M J Fowler
- Vivian L. Smith Department of Neurosurgery, McGovern Medical School/University of Texas Health Science Center at Houston, Houston, TX 77030, United States of America
| | - J D Cotter
- Vivian L. Smith Department of Neurosurgery, McGovern Medical School/University of Texas Health Science Center at Houston, Houston, TX 77030, United States of America
| | - B E Knight
- Vivian L. Smith Department of Neurosurgery, McGovern Medical School/University of Texas Health Science Center at Houston, Houston, TX 77030, United States of America
| | - E M Sevick-Muraca
- Brown Foundation Institute of Molecular Medicine, Center for Molecular Imaging, Houston, TX 77030, United States of America
| | - D I Sandberg
- Vivian L. Smith Department of Neurosurgery, McGovern Medical School/University of Texas Health Science Center at Houston, Houston, TX 77030, United States of America; Department of Pediatric Surgery, McGovern Medical School/University of Texas Health Science Center at Houston, Houston, TX 77030, United States of America; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, United States of America
| | - R W Sirianni
- Vivian L. Smith Department of Neurosurgery, McGovern Medical School/University of Texas Health Science Center at Houston, Houston, TX 77030, United States of America.
| |
Collapse
|
|
6
|
Recent advances in polymer-based drug delivery systems for local anesthetics. Acta Biomater 2019; 96:55-67. [PMID: 31152941 DOI: 10.1016/j.actbio.2019.05.044] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2018] [Revised: 05/16/2019] [Accepted: 05/19/2019] [Indexed: 12/19/2022]
Abstract
Local anesthetics, which cause temporary loss of pain by inhibiting the transmission of nerve impulses, have been widely used in clinical practice. However, neurotoxicity and short half-lives have significantly limited their clinical applications. To overcome those barriers, numerous drug delivery systems (DDS) have been designed to encapsulate local anesthetic agents, so that large doses can be released slowly and provide analgesia over a prolonged period. So far, multiple classes of local anesthetic carriers have been investigated, with some of them already on the market. Among those, polymer-based delivery platforms are the most extensively explored, especially in the form of polymeric nanoparticle carriers. This review gives a specific focus on the most commonly used natural and synthetic polymers for local anesthetics delivery, owing to their excellent biocompatibility, biodegradability and versatility. State-of-the-art studies concerning such polymer delivery systems have been discussed in depth. We also highlight the impact of those delivery platforms as well as some key challenges that need to be overcome for their broader clinical applications. STATEMENT OF SIGNIFICANCE: Currently, local anesthetics have been widely used in clinically practices to prevent transmission of nerve impulses. However, the applications of anesthetics are greatly limited due to their neurotoxicity and short half-lives. Moreover, it is difficult to maintain frequent administrations which can cause poor compliance and serious consequences. Numerous drug delivery systems have been developed to solve those issues. In this review, we highlight the recent advances in polymer-based drug delivery systems for local anesthetics. The advantages as well as shortcomings for different types of polymer-based drug delivery systems are summarized in this paper. In the end, we also give prospects for future development of polymer drug delivery systems for anesthetics.
Collapse
|
|
7
|
Yasmin N, Ishitsuka Y, Fukaura M, Yamada Y, Nakahara S, Ishii A, Kondo Y, Takeo T, Nakagata N, Motoyama K, Higashi T, Okada Y, Nishikawa J, Ichikawa A, Iohara D, Hirayama F, Higaki K, Ohno K, Matsuo M, Irie T. In Vitro and In Vivo Evaluation of 6-O-α-Maltosyl-β-Cyclodextrin as a Potential Therapeutic Agent Against Niemann-Pick Disease Type C. Int J Mol Sci 2019; 20:ijms20051152. [PMID: 30845767 PMCID: PMC6429330 DOI: 10.3390/ijms20051152] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 02/27/2019] [Accepted: 02/28/2019] [Indexed: 01/07/2023] Open
Abstract
Niemann-Pick disease Type C (NPC) is a rare lysosomal storage disease characterized by the dysfunction of intracellular cholesterol trafficking with progressive neurodegeneration and hepatomegaly. We evaluated the potential of 6-O-α-maltosyl-β-cyclodextrin (G2-β-CD) as a drug candidate against NPC. The physicochemical properties of G2-β-CD as an injectable agent were assessed, and molecular interactions between G2-β-CD and free cholesterol were studied by solubility analysis and two-dimensional proton nuclear magnetic resonance spectroscopy. The efficacy of G2-β-CD against NPC was evaluated using Npc1 deficient Chinese hamster ovary (CHO) cells and Npc1 deficient mice. G2-β-CD in aqueous solution showed relatively low viscosity and surface activity; characteristics suitable for developing injectable formulations. G2-β-CD formed higher-order inclusion complexes with free cholesterol. G2-β-CD attenuated dysfunction of intercellular cholesterol trafficking and lysosome volume in Npc1 deficient CHO cells in a concentration dependent manner. Weekly subcutaneous injections of G2-β-CD (2.9 mmol/kg) ameliorated abnormal cholesterol metabolism, hepatocytomegaly, and elevated serum transaminases in Npc1 deficient mice. In addition, a single cerebroventricular injection of G2-β-CD (21.4 μmol/kg) prevented Purkinje cell loss in the cerebellum, body weight loss, and motor dysfunction in Npc1 deficient mice. In summary, G2-β-CD possesses characteristics favorable for injectable formulations and has therapeutic potential against in vitro and in vivo NPC models.
Collapse
Affiliation(s)
- Nushrat Yasmin
- Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
- Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Yoichi Ishitsuka
- Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Madoka Fukaura
- Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
- Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Yusei Yamada
- Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Shuichi Nakahara
- Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Akira Ishii
- Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Yuki Kondo
- Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Toru Takeo
- Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
| | - Naomi Nakagata
- Division of Reproductive Engineering, Center for Animal Resources and Development (CARD), Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
| | - Keiichi Motoyama
- Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Taishi Higashi
- Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| | - Yasuyo Okada
- Institute Biosciences, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan.
| | - Junichi Nishikawa
- Institute Biosciences, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan.
| | - Atsushi Ichikawa
- Institute Biosciences, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, 11-68 Koshien Kyuban-cho, Nishinomiya 663-8179, Japan.
| | - Daisuke Iohara
- Laboratory of Physical Pharmaceutics, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
| | - Fumitoshi Hirayama
- Laboratory of Physical Pharmaceutics, Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
| | - Katsumi Higaki
- Division of Functional Genomics, Research Center for Bioscience and Technology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan.
| | - Kousaku Ohno
- Sanin Rosai Hospital, 1-8-1, Kaikeshinden, Yonago 683-8605, Japan.
| | - Muneaki Matsuo
- Department of Pediatrics, Faculty of Medicine, Saga University, 5-1-1, Nabeshima, Saga 849-8501, Japan.
| | - Tetsumi Irie
- Department of Clinical Chemistry and Informatics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
- Program for Leading Graduate Schools "HIGO (Health life science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
| |
Collapse
|
|
8
|
Bragagni M, Gil-Alegre ME, Mura P, Cirri M, Ghelardini C, Di Cesare Mannelli L. Improving the therapeutic efficacy of prilocaine by PLGA microparticles: Preparation, characterization and in vivo evaluation. Int J Pharm 2018; 547:24-30. [DOI: 10.1016/j.ijpharm.2018.05.054] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Revised: 05/21/2018] [Accepted: 05/22/2018] [Indexed: 11/28/2022]
|
|
9
|
Emelife PI, Eng MR, Menard BL, Myers AS, Cornett EM, Urman RD, Kaye AD. Adjunct medications for peripheral and neuraxial anesthesia. Best Pract Res Clin Anaesthesiol 2018; 32:83-99. [PMID: 30322466 DOI: 10.1016/j.bpa.2018.06.011] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Accepted: 06/18/2018] [Indexed: 02/06/2023]
Abstract
Regional and neuraxial anesthesia can provide a safer perioperative experience, greater satisfaction, reduced opioid consumption, and reduction of pain, while minimizing side effects. Ultrasound technology has aided clinicians in depositing local anesthetic medication in precise proximity to targeted peripheral nerves. There are a plethora of adjuvants that have been utilized to prolong local anesthetic actions and enhance effects in peripheral nerve blocks. This manuscript describes the current state of the use of adjuncts, e.g., dexmedetomidine, dexamethasone, clonidine, epinephrine, etc., in regional anesthesia. Additionally, evidence behind dosing and block prolongation is summarized along with patient outcomes, adverse effects, and future directions.
Collapse
Affiliation(s)
- Patrick Ifesinachi Emelife
- Department of Anesthesiology, LSU Health Sciences Center, Room 653, 1542 Tulane Ave., New Orleans, LA, 70112, USA.
| | - Matthew R Eng
- Department of Anesthesiology, LSU Health Sciences Center, Room 656, 1542 Tulane Ave., New Orleans, LA, 70112, USA.
| | - Bethany L Menard
- Department of Anesthesiology, LSU Health Sciences Center, Room 656, 1542 Tulane Ave., New Orleans, LA, 70112, USA.
| | - Andrew S Myers
- LSU Health Sciences Center, 433 Bolivar St., New Orleans, LA, 70112, USA.
| | - Elyse M Cornett
- Department of Anesthesiology, LSU Health Shreveport, 1501 Kings Highway, Shreveport, LA, 71103, USA.
| | - Richard D Urman
- Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School, Brigham and Women's Hospital, 75 Francis St, Boston, MA, 02115, USA.
| | - Alan D Kaye
- Department of Anesthesiology, LSU Health Sciences Center, Room 653, 1542 Tulane Ave., New Orleans, LA, 70112, USA.
| |
Collapse
|
|
10
|
Swain A, Nag DS, Sahu S, Samaddar DP. Adjuvants to local anesthetics: Current understanding and future trends. World J Clin Cases 2017; 5:307-323. [PMID: 28868303 PMCID: PMC5561500 DOI: 10.12998/wjcc.v5.i8.307] [Citation(s) in RCA: 120] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2017] [Revised: 05/03/2017] [Accepted: 05/19/2017] [Indexed: 02/05/2023] Open
Abstract
Although beneficial in acute and chronic pain management, the use of local anaesthetics is limited by its duration of action and the dose dependent adverse effects on the cardiac and central nervous system. Adjuvants or additives are often used with local anaesthetics for its synergistic effect by prolonging the duration of sensory-motor block and limiting the cumulative dose requirement of local anaesthetics. The armamentarium of local anesthetic adjuvants have evolved over time from classical opioids to a wide array of drugs spanning several groups and varying mechanisms of action. A large array of opioids ranging from morphine, fentanyl and sufentanyl to hydromorphone, buprenorphine and tramadol has been used with varying success. However, their use has been limited by their adverse effect like respiratory depression, nausea, vomiting and pruritus, especially with its neuraxial use. Epinephrine potentiates the local anesthetics by its antinociceptive properties mediated by alpha-2 adrenoreceptor activation along with its vasoconstrictive properties limiting the systemic absorption of local anesthetics. Alpha 2 adrenoreceptor antagonists like clonidine and dexmedetomidine are one of the most widely used class of local anesthetic adjuvants. Other drugs like steroids (dexamethasone), anti-inflammatory agents (parecoxib and lornoxicam), midazolam, ketamine, magnesium sulfate and neostigmine have also been used with mixed success. The concern regarding the safety profile of these adjuvants is due to its potential neurotoxicity and neurological complications which necessitate further research in this direction. Current research is directed towards a search for agents and techniques which would prolong local anaesthetic action without its deleterious effects. This includes novel approaches like use of charged molecules to produce local anaesthetic action (tonicaine and n butyl tetracaine), new age delivery mechanisms for prolonged bioavailability (liposomal, microspheres and cyclodextrin systems) and further studies with other drugs (adenosine, neuromuscular blockers, dextrans).
Collapse
|
|
11
|
Santamaria CM, Woodruff A, Yang R, Kohane DS. Drug delivery systems for prolonged duration local anesthesia. MATERIALS TODAY (KIDLINGTON, ENGLAND) 2017; 20:22-31. [PMID: 28970739 PMCID: PMC5621744 DOI: 10.1016/j.mattod.2016.11.019] [Citation(s) in RCA: 83] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/18/2023]
Abstract
Numerous drug delivery systems have been applied to the problem of providing prolonged duration local anesthesia (PDLA). Here we review the rationale for PDLA, the desirable features for and important attributes of such systems, and specific examples that have been developed.
Collapse
Affiliation(s)
- Claudia M Santamaria
- Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, United States
| | - Alan Woodruff
- Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, United States
| | - Rong Yang
- Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, United States
| | - Daniel S Kohane
- Laboratory for Biomaterials and Drug Delivery, Division of Critical Care Medicine, Department of Anesthesiology, Boston Children's Hospital, Boston, Massachusetts, United States
| |
Collapse
|
|
12
|
Novel methods of local anesthetic delivery in the perioperative and postoperative setting—potential for fibrin hydrogel delivery. J Clin Anesth 2016; 35:246-252. [DOI: 10.1016/j.jclinane.2016.07.033] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2016] [Revised: 06/19/2016] [Accepted: 07/11/2016] [Indexed: 11/22/2022]
|
|
13
|
Maestrelli F, Bragagni M, Mura P. Advanced formulations for improving therapies with anti-inflammatory or anaesthetic drugs: A review. J Drug Deliv Sci Technol 2016. [DOI: 10.1016/j.jddst.2015.09.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
|
|
14
|
Golovanevski L, Ickowicz D, Sokolsky-Papkov M, Domb A, Weiniger CF. In vivo study of an extended release bupivacaine formulation following site-directed nerve injection. J BIOACT COMPAT POL 2014. [DOI: 10.1177/0883911514560662] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Site-directed administration of local anesthetic agents incorporated into a slow controlled-release injectable implant prolongs the analgesic effect. However, there are potential neuro- and myotoxic consequences. We evaluated a local anesthetic agent (bupivacaine) loaded into a slow-release biodegradable polymer based on castor oil and poly(lactic acid). The formulation was applied directly to the sciatic nerve area in female imprinting control region mice along with appropriate controls. Local nerve and muscle and systemic toxicity were evaluated over a 3-month period following injection of 0.05, 0.1, and 0.125 mL of the 15% bupivacaine–polymer formulation. Histological samples were prepared and examined; no signs of severe inflammation were observed. Histological inflammation signs were more prominent in both nerves and muscles following application of the largest volumes of the polymer formulation (0.1 and 0.125 mL). Following application of 0.1 mL, 15% bupivacaine–polymer formulation, maximal changes were seen in nerve samples two days and two weeks after injection, with complete resolution one month following injection. Neither blank polymer nor plain bupivacaine 0.5% caused any histological changes. Local nerve and muscle toxicity were affected by duration the of exposure and dose of the local anesthetic agent. However, there were clear indications of time-related healing process 3 months after injection.
Collapse
Affiliation(s)
- Ludmila Golovanevski
- Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
| | - Diana Ickowicz
- Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Marina Sokolsky-Papkov
- Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
- Center for Nanotechnology in Drug Delivery, School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Abraham Domb
- Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Carolyn F Weiniger
- Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- Department of Anesthesia, Stanford School of Medicine, Stanford, CA, USA
| |
Collapse
|
|
15
|
Serpe L, Franz-Montan M, Santos CPD, Silva CBD, Nolasco FP, Caldas CS, Volpato MC, Paula ED, Groppo FC. Anaesthetic efficacy of bupivacaine 2-hydroxypropyl-β-cyclodextrin for dental anaesthesia after inferior alveolar nerve block in rats. Br J Oral Maxillofac Surg 2014; 52:452-7. [PMID: 24673836 DOI: 10.1016/j.bjoms.2014.02.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2013] [Accepted: 02/21/2014] [Indexed: 11/26/2022]
Abstract
Bupivacaine is a long-acting local anaesthetic that is widely used in medicine and dentistry. The duration and intensity of its sensory blockade in animal models is increased by its inclusion in complexes with cyclodextrins. The aim of the present study was to evaluate the anaesthetic efficacy of bupivacaine 2-hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex for dental anaesthesia after inferior alveolar nerve block in rats. Thirty rats were each given an injection close to the mandibular foramen of 0.2ml of one of the following formulations: 0.5% bupivacaine alone; 0.5% bupivacaine with 1:200,000 epinephrine; and 0.5% bupivacaine-HPβCD inclusion complex (bupivacaine-HPβCD). The other sides were used as controls, with either 0.9% saline or anaesthetic-free HPβCD solution being injected. The onset, success, and duration of pulpal anaesthesia were assessed by electrical stimulation ("pulp tester") on inferior molars. Results were analysed using ANOVA (Tukey), log rank, and chi square tests (α=5%). There were no differences among the formulations in onset of anaesthesia (p=0.59) or between the bupivacaine plus epinephrine and bupivacaine plus HPβCD in duration of anaesthesia, but bupivacaine plus epinephrine gave significantly higher values than bupivacaine alone (p=0.007). Bupivacaine plus epinephrine was a better anaesthetic than bupivacaine alone (p=0.02), while Bupi-HPβCD gave intermediate results, and therefore did not differ significantly from the other 2 groups (p=0.18 with bupivacaine alone; and p=0.44 with bupivacaine plus epinephrine). The bupivacaine-HPβCD complex showed similar anaesthetic properties to those of bupivacaine with epinephrine.
Collapse
Affiliation(s)
- L Serpe
- Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
| | - M Franz-Montan
- Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
| | - C P dos Santos
- Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
| | - C B da Silva
- Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
| | - F P Nolasco
- Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
| | - C S Caldas
- Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
| | - M C Volpato
- Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
| | - E de Paula
- Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil
| | - F C Groppo
- Department of Physiological Sciences, Piracicaba Dental School, University of Campinas - UNICAMP, Piracicaba, São Paulo, Brazil.
| |
Collapse
|
|
16
|
McAlvin JB, Kohane DS. Prolonged Duration Local Anesthesia. ADVANCES IN DELIVERY SCIENCE AND TECHNOLOGY 2014. [DOI: 10.1007/978-1-4614-9434-8_28] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
|
|
17
|
McAlvin JB, Reznor G, Shankarappa SA, Stefanescu CF, Kohane DS. Local toxicity from local anesthetic polymeric microparticles. Anesth Analg 2013; 116:794-803. [PMID: 23460564 DOI: 10.1213/ane.0b013e31828174a7] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Local tissue injury from sustained-release formulations for local anesthetics can be severe. There is considerable variability in reporting of that injury. We investigated the influence of the intrinsic myotoxicity of the encapsulated local anesthetic (lidocaine, low; bupivacaine, high) on tissue reaction in rats. METHODS Cytotoxicity from a range of lidocaine and bupivacaine concentrations was measured in C2C12 myotubes over 6 days. Rats were given sciatic nerve blocks with 4 microparticulate formulations of lidocaine and bupivacaine: 10% (w/w) lidocaine poly(lactic-co-glycolic) acid (PLGA), 10% (w/w) bupivacaine PLGA, 50% (w/w) lidocaine PLGA, and 50% (w/w) bupivacaine PLGA. Effectiveness of nerve blockade was assessed by a modified hotplate test and weightbearing measurements. Myotoxicity was scored in histologic sections of injection sites. Bupivacaine and lidocaine release kinetics from the particles were measured. RESULTS Median sensory blockade duration for 50% (w/w) lidocaine was 255 (90-540) minutes versus 840 (277-1215) minutes for 50% (w/w) bupivacaine (P = 0.056). All microparticulate formulations resulted in myotoxicity. The choice of local anesthetic did not influence the severity of myotoxicity. Median myotoxicity scores for 50% (w/w) lidocaine compared with 50% (w/w) bupivacaine at 4 days were 3.4 (2.1-4.2) vs 3.3 (2.9-3.5) (P = 0.44) and at 14 days 1.9 (1.8-2.4) vs 1.7 (1.3-1.9) (P = 0.23), respectively. CONCLUSIONS Lidocaine and bupivacaine PLGA microspheres resulted in similar degrees of myotoxicity, irrespective of drug loading. Intrinsic myotoxicity did not predict tissue injury from sustained release of these anesthetics. Caution is warranted in the use of such devices near muscle and nerve.
Collapse
Affiliation(s)
- J Brian McAlvin
- Department of Medicine, Medicine Critical Care Program, Children’s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
| | | | | | | | | |
Collapse
|
|
18
|
de Paula E, Cereda CMS, Fraceto LF, de Araújo DR, Franz-Montan M, Tofoli GR, Ranali J, Volpato MC, Groppo FC. Micro and nanosystems for delivering local anesthetics. Expert Opin Drug Deliv 2012; 9:1505-24. [DOI: 10.1517/17425247.2012.738664] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
|
|
19
|
Prolonged analgesia from Bupisome and Bupigel formulations: From design and fabrication to improved stability. J Control Release 2012; 160:346-52. [DOI: 10.1016/j.jconrel.2011.12.030] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2012] [Revised: 12/18/2011] [Accepted: 12/21/2012] [Indexed: 11/23/2022]
|
|
20
|
Weiniger CF, Golovanevski L, Domb AJ, Ickowicz D. Extended release formulations for local anaesthetic agents. Anaesthesia 2012; 67:906-16. [PMID: 22607613 DOI: 10.1111/j.1365-2044.2012.07168.x] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Systemic toxicity through overdose of local anaesthetic agents is a real concern. By encapsulating local anaesthetics in biodegradable carriers to produce a system for prolonged release, their duration of action can be extended. This encapsulation should also improve the safety profile of the local anaesthetic as it is released at a slower rate. Work with naturally occurring local anaestheticss has also shown promise in the area of reducing systemic and neurotoxicity. Extended duration local anaesthetic formulations in current development or clinical use include liposomes, hydrophobic based polymer particles such as Poly(lactic-co-glycolic acid) microspheres, pasty injectable and solid polymers like Poly(sebacic-co-ricinoleic acid) P(SA:RA) and their combination with synthetic and natural local anaesthetic. Their duration of action, rationale and limitations are reviewed. Direct comparison of the different agents is limited by their chemical properties, the drug doses encapsulated and the details of in vivo models described.
Collapse
Affiliation(s)
- C F Weiniger
- Department of Anesthesiology and Critical Care Medicine, Hadassah Hebrew University Medical Centre, Jerusalem, Israel.
| | | | | | | |
Collapse
|
|
21
|
Weiniger CF, Golovanevski M, Sokolsky-Papkov M, Domb AJ. Review of prolonged local anesthetic action. Expert Opin Drug Deliv 2010; 7:737-52. [PMID: 20408748 DOI: 10.1517/17425241003767383] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
IMPORTANCE OF THE FIELD Pain following surgery is often treated by local anesthetic agents. Duration of the analgesia can be extended safely following administration of encapsulated large doses of local anesthetic agents. AREAS COVERED IN THIS REVIEW This review considers formulations used for encapsulation of local anesthetic agents for prolonged anesthesia effect. All studies describing encapsulation of a commercial local anesthetic agent for providing prolonged analgesia were considered using the NCBI Medline site. of local anesthetic, prolonged anesthesia, polymers and liposomes were entered in order to retrieve appropriate articles and reviews from 1966 to 2010, with emphasis on the last 10 years. Reference pages were searched manually for other relevant articles. The topics covered include an overview of local anesthetic agents and a review of local anesthetic carrier agents, with emphasis on liposomes and polymer carriers. Articles were limited to the English language. WHAT THE READER WILL GAIN The current research areas for prolongation of local anesthetic effect are evaluated, along with their limitations. Each topic has been summarized, and the review has attempted to cover all current laboratory and clinical studies in a simple manner that should also be useful for readers without a pharmacology background. The direction of research is promising and exciting, and this review should be a useful up-to-date reference. TAKE HOME MESSAGE Many formulations including polymer and liposome carriers have facilitated prolonged local anesthetic action for several days, although few clinical studies have been performed. This field promises a safe way to deliver local anesthetics for effect far beyond that of commercially available agents, with potential cost and health benefits for patients suffering chronic or postoperative pain.
Collapse
Affiliation(s)
- Carolyn F Weiniger
- Hadassah Hebrew University Medical Center, Department of Anesthesiology and Critical Care Medicine, Jerusalem, POB 12000, Israel.
| | | | | | | |
Collapse
|
|
22
|
|
|
23
|
Antiprion action of new cyclodextrin analogues. Biochim Biophys Acta Gen Subj 2009; 1790:1382-6. [PMID: 19631725 DOI: 10.1016/j.bbagen.2009.07.011] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2009] [Revised: 07/08/2009] [Accepted: 07/10/2009] [Indexed: 11/22/2022]
Abstract
BACKGROUND Prion disorders are characterised by the accumulation of a misfolded isoform (PrPSc) of the host encoded prion protein (PrPC). This paper examines the antiprion potential of cyclodextrin (CD) analogues and it identifies sulphated-beta-cyclodextrin, with a half-maximal inhibitory concentration (IC50) of 2.4 microM, as having 31-fold greater antiprion activity than that previously reported for beta-cyclodextrin (betaCD). METHODS Scrapie infected cells were treated with a range of betaCD analogues. This enabled a CD structure to antiprion activity analysis to be carried out. The metachromatic activity of each of the cyclodextrins was determined, this test is employed to mimic complexation of glycosaminogylcans to a cell membrane. RESULTS Sulphated-betaCD had an IC50 of 2.4 microM and it was the only CD found to have metachromatic activity. Its activity was equivalent to that of heparin and heparin sulphate, this may account for sulphated-betaCD's superior antiprion action. GENERAL SIGNIFICANCE In solution heparin can form a helical structure with a hydrophobic interior, the hydrophobic interior of cyclic CDs is vital for CD molecule encapsulation. The controlled CD structure, however, restricts degradation by human enzymes; consequently sulphated-CDs could be ideal candidates in the search for prion therapeutics. Sulphated-CDs may open up avenues for the treatment of TSEs.
Collapse
|
|
24
|
de Araujo DR, Tsuneda SS, Cereda CM, Del G.F. Carvalho F, Preté PS, Fernandes SA, Yokaichiya F, Franco MK, Mazzaro I, Fraceto LF, de F.A. Braga A, de Paula E. Development and pharmacological evaluation of ropivacaine-2-hydroxypropyl-β-cyclodextrin inclusion complex. Eur J Pharm Sci 2008; 33:60-71. [DOI: 10.1016/j.ejps.2007.09.010] [Citation(s) in RCA: 117] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2007] [Revised: 09/11/2007] [Accepted: 09/28/2007] [Indexed: 11/30/2022]
|