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Sulaiman M, Lukitaningsih E, Martien R, Wirohadidjojo YW, Danarti R. Nanotechnology in Infantile Hemangioma Management. J Pediatr Pharmacol Ther 2025; 30:27-46. [PMID: 39935564 PMCID: PMC11809533 DOI: 10.5863/1551-6776-30.1.27] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Accepted: 01/31/2024] [Indexed: 02/13/2025]
Abstract
Infantile hemangioma (IH) is the most prevalent benign vascular tumor among infants. While most hemangioma cases typically undergo spontaneous resolution, there is a risk of complications and concern over changes in appearance in certain circumstances. The treatment options include oral and topical drug therapy, laser therapy, and surgery. Because the lesions are (but not exclusively) formed on the skin's surface and exhibit features typical of tumors, there are opportunities for implementing nanoparticle technology for systemic and topical treatments. Nanotechnology in drug delivery generally aims to boost the efficacy of substance penetration or absorption, prevent systemic side effects by passive or active targeting, prolong effectiveness, and reduce the dose and duration of treatment. Several types of nanoparticles have been selected as research subjects in nanoparticle-based studies for treating IH. The type of nanoparticle is chosen based on evaluations of many factors, such as the active substance's physical and chemical compatibility, target site, and route of administration, and the formula is constructed by using an optimization process, resulting in a system with distinctive advantages.
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Affiliation(s)
- Muhammad Sulaiman
- Doctoral Program (MS), Faculty of Pharmacy, Department of Pharmaceutical Chemistry (EL, RM), Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia; Department of Dermatology and Venereology (YWW, RD), Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia
| | - Endang Lukitaningsih
- Doctoral Program (MS), Faculty of Pharmacy, Department of Pharmaceutical Chemistry (EL, RM), Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia; Department of Dermatology and Venereology (YWW, RD), Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia
| | - Ronny Martien
- Doctoral Program (MS), Faculty of Pharmacy, Department of Pharmaceutical Chemistry (EL, RM), Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia; Department of Dermatology and Venereology (YWW, RD), Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia
| | - Yohanes Widodo Wirohadidjojo
- Doctoral Program (MS), Faculty of Pharmacy, Department of Pharmaceutical Chemistry (EL, RM), Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia; Department of Dermatology and Venereology (YWW, RD), Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia
| | - Retno Danarti
- Doctoral Program (MS), Faculty of Pharmacy, Department of Pharmaceutical Chemistry (EL, RM), Faculty of Pharmacy, Gadjah Mada University, Yogyakarta, Indonesia; Department of Dermatology and Venereology (YWW, RD), Faculty of Medicine, Public Health and Nursing, Gadjah Mada University, Yogyakarta, Indonesia
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Dong J, Cui J, Shi X, Wang T, Liu S. Itraconazole inhibits proliferation, induces apoptosis, and reduces angiogenesis of hemangioma endothelial cells by downregulating the hedgehog signaling pathway. Heliyon 2023; 9:e19244. [PMID: 37674841 PMCID: PMC10477473 DOI: 10.1016/j.heliyon.2023.e19244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 07/31/2023] [Accepted: 08/16/2023] [Indexed: 09/08/2023] Open
Abstract
Infantile hemangioma (IH) is among the most prevalent benign vascular tumours in infants. The pathogenesis of IH mainly involves abnormal proliferation of vascular endothelial cells and the formation of new vessels. Itraconazole was shown to be effective in treating IH; however, the mechanism underlying its action is still unclear. The purpose of this study was to examine the effects of itraconazole on the proliferation, apoptosis, and angiogenesis of hemangioma endothelial cells (HemECs); human umbilical vein endothelial cells served as the control group. The expression of genes involved in the hedgehog (HH) signaling pathway (SHH, PTCH1, SMO, and GLI1) was determined using real-time quantitative polymerase chain reaction. Western blotting was used to determine the expression of related proteins. In this study, itraconazole significantly dose- and time-dependently inhibited the viability of HemECs. Itraconazole suppressed the expression of PCNA, Ki67, and vascular endothelial growth factor (VEGF), demonstrating that this treatment inhibited cell proliferation and angiogenesis. Moreover, itraconazole induced apoptosis of HemECs by activating the expression of BAX and inhibiting the expression of BCL2. Itraconazole inhibited SHH, PTCH1, SMO, and GLI1 expression. Activation of the HH pathway by recombinant human sonic hedgehog (rhSHH) protein attenuated the effect of itraconazole on HemECs. In conclusion, itraconazole inhibits proliferation, induces apoptosis, and reduces angiogenesis of HemECs via the downregulation of the HH signaling pathway. Therefore, itraconazole may be an alternative choice for the treatment of IH.
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Affiliation(s)
- Jianyong Dong
- Department of Oral and Maxillofacial Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
- Gao Xin Branch, Jinan Stomatological Hospital, Jinan, Shandong 250101, China
| | - Jun Cui
- Department of Dental Implantology, Central Laboratory, Jinan Stomatological Hospital, Jinan, Shandong 250001, China
| | - Xuanxuan Shi
- Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China
| | - Tao Wang
- Department of Oral and Maxillofacial Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
| | - Shaohua Liu
- Department of Oral and Maxillofacial Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China
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Kong M, Li Y, Wang K, Zhang S, Ji Y. Infantile hemangioma models: is the needle in a haystack? J Transl Med 2023; 21:308. [PMID: 37149592 PMCID: PMC10163722 DOI: 10.1186/s12967-023-04144-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Accepted: 04/20/2023] [Indexed: 05/08/2023] Open
Abstract
Infantile hemangioma (IH) is the most prevalent benign vascular tumor in infants, with distinct disease stages and durations. Despite the fact that the majority of IHs can regress spontaneously, a small percentage can cause disfigurement or even be fatal. The mechanisms underlying the development of IH have not been fully elucidated. Establishing stable and reliable IH models provides a standardized experimental platform for elucidating its pathogenesis, thereby facilitating the development of new drugs and the identification of effective treatments. Common IH models include the cell suspension implantation model, the viral gene transfer model, the tissue block transplantation model, and the most recent three-dimensional (3D) microtumor model. This article summarizes the research progress and clinical utility of various IH models, as well as the benefits and drawbacks of each. Researchers should select distinct IH models based on their individual research objectives to achieve their anticipated experimental objectives, thereby increasing the clinical relevance of their findings.
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Affiliation(s)
- Meng Kong
- Division of Oncology, Department of Pediatric Surgery, West China Hospital, Sichuan University, #37# Guo-Xue-Xiang, Chengdu, 610041 China
| | - Yanan Li
- Division of Oncology, Department of Pediatric Surgery, West China Hospital, Sichuan University, #37# Guo-Xue-Xiang, Chengdu, 610041 China
| | - Kai Wang
- Division of Oncology, Department of Pediatric Surgery, West China Hospital, Sichuan University, #37# Guo-Xue-Xiang, Chengdu, 610041 China
| | - Shisong Zhang
- Department of Pediatric Surgery, Children’s Hospital Affiliated to Shandong University, #23976# Jingshi Road, Jinan, 250022 China
| | - Yi Ji
- Division of Oncology, Department of Pediatric Surgery, West China Hospital, Sichuan University, #37# Guo-Xue-Xiang, Chengdu, 610041 China
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Rocha JL, Pires FQ, Gross IP, Alencar-Silva T, Gratieri T, Gelfuso GM, Sá-Barreto L, Carvalho JL, Cunha-Filho M. Propranolol-loaded nanostructured lipid carriers for topical treatment of infantile hemangioma. J Drug Deliv Sci Technol 2022. [DOI: 10.1016/j.jddst.2022.104099] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Efficacy and Safety of Propranolol Cream in Infantile Hemangioma: A Prospective Pilot Study. J Pharmacol Sci 2022; 149:60-65. [DOI: 10.1016/j.jphs.2022.03.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 03/09/2022] [Accepted: 03/22/2022] [Indexed: 11/19/2022] Open
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Carvalho F, Liberal M, Vale F, Rodrigues Santos N, Guedes R. Early Presentation of an Ulcerated Infantile Haemangioma in a Newborn. Cureus 2022; 14:e21545. [PMID: 35223318 PMCID: PMC8864578 DOI: 10.7759/cureus.21545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/23/2022] [Indexed: 11/05/2022] Open
Abstract
Infantile haemangiomas (IHs) are the most common benign soft tissue tumours in children. Usually, they evolve without clinical incurrences and regression of the lesion can occur spontaneously in the first years of life. The decision for treatment is dependent upon the intrinsic characteristics of the lesion such as location, extension, functional compromise and complications. We present the case of a newborn who was clinically accessed during ambulatory routine consultation when a lesion with 5x5 centimetres compatible with an IH was first observed. Inflammatory signs with no active bleeding were present and the newborn displayed signs of discomfort during a diaper change and manipulation of the anogenital area. For this reason, a referral was made for observation in a central hospital with specialised paediatrics, paediatric surgery and dermatology support. A 10-day antibiotic course with flucloxacillin and local topical care with silver sulfadiazine cream and barrier cream with zinc oxide were adopted, achieving a good clinical outcome. Laboratory workup, cardiovascular assessment, imagiological investigation with abdominopelvic and spinal cord ultrasonography as well as lumbosacral magnetic resonance imaging were all normal. Ulceration is the most prevalent complication of IHs and it is associated with pain, recurrent bleeding, infection and difficult scarring, thus early recognition and directed treatment are essential to achieve a good clinical outcome.
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Butacu AI, Negulet IE, Boieriu ED, Dinu IS, Mihalache A, Mastalier B, Salavastru CM, Fritz K, Tiplica GS. [The most common benign cutaneous neoplasms of vascular, muscular, and adipose tissue and their treatment]. Hautarzt 2022; 73:104-113. [PMID: 35041024 DOI: 10.1007/s00105-021-04926-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/26/2021] [Indexed: 11/30/2022]
Abstract
Benign cutaneous vascular and cutaneous neoplasms arising from muscle or adipose tissue are rare. Their definition and classification are still controversially discussed. Histopathological and immunohistochemical studies, together with the new genetic tests, contribute significantly to the correct description of the various benign neoplasms of cutaneous origin. Clarifying whether a lesion is benign is fundamental for prognosis and therapeutic management. In most cases, surgical excision is the treatment of choice. Dermatologists should be familiar with the classifications of the most common benign cutaneous neoplasms of vascular, muscular, and adipose tissue and be able to recommend the procedures currently used for an accurate diagnosis. Ensuring that a lesion is benign and a good surgical outcome are essential for the patient.
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Affiliation(s)
- Alexandra-Irina Butacu
- Dermatologie II, Colentina Klinik, Carol-Davila-Universität für Medizin und Pharmazie, Bukarest, Rumänien
| | - Iulia-Elena Negulet
- Dermatologie II, Colentina Klinik, Carol-Davila-Universität für Medizin und Pharmazie, Bukarest, Rumänien
| | - Emanuela-Domnica Boieriu
- Dermatologie II, Colentina Klinik, Carol-Davila-Universität für Medizin und Pharmazie, Bukarest, Rumänien
| | - Ioana-Simona Dinu
- Dermatologie II, Colentina Klinik, Carol-Davila-Universität für Medizin und Pharmazie, Bukarest, Rumänien
| | | | - Bogdan Mastalier
- Chirurgie I, Colentina Klinik, Carol-Davila-Universität für Medizin und Pharmazie, Stefan cel Mare Street, 19-21, 020125, Bukarest, Rumänien.
| | - Carmen Maria Salavastru
- Pädiatrische Dermatologie, Institut für Dermatoonkologische Forschung, Colentina Klinik, Carol-Davila-Universität für Medizin und Pharmazie, Bukarest, Rumänien
| | - Klaus Fritz
- Dermatologie II, Colentina Klinik, Carol-Davila-Universität für Medizin und Pharmazie, Bukarest, Rumänien
| | - George-Sorin Tiplica
- Dermatologie II, Colentina Klinik, Carol-Davila-Universität für Medizin und Pharmazie, Bukarest, Rumänien
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Abstract
Infantile hemangioma (IH) is the most common benign vascular tumor of infancy, affecting about 5% of infants. It has a characteristic growth pattern of early rapid proliferation followed by progressive involution. Although most IH evolve favorably, complications are observed in 10-15% of cases, justifying treatment. For over 10 years now, propranolol has become the first-line therapy for complicated IH, revolutionizing their management and their prognosis. In this article, we review the clinical features, associations, complications/sequelae and therapeutic approaches for IH, focusing on current medical therapy. Indications for treatment and various treatment options, including propranolol and other oral β-blockers, topical timolol, and corticosteroids are presented. Current controversies regarding oral propranolol such as pre-treatment screening, in- vs out-patient initiation of treatment, early and potential long-term side effects and recommended monitoring are discussed.
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Affiliation(s)
- Caroline Colmant
- Division of Pediatric Dermatology, Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal, QC, Canada.
| | - Julie Powell
- Division of Pediatric Dermatology, Department of Pediatrics, Sainte-Justine University Hospital Center, University of Montreal, Montreal, QC, Canada
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Liu Z, Lv S, Wang S, Qu SM, Zhang GY, Lin YT, Yang L, Li FQ. Itraconazole therapy for infant hemangioma: Two case reports. World J Clin Cases 2021; 9:8579-8586. [PMID: 34754871 PMCID: PMC8554448 DOI: 10.12998/wjcc.v9.i28.8579] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 07/05/2021] [Accepted: 07/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Infantile hemangiomas (IHs) are the most common childhood benign tumors, showing distinctive progression characteristics and outcomes. Due to the high demand for aesthetics among parents of IH babies, early intervention is critical in some cases. β-Adrenergic blockers and corticosteroids are first-line medications for IHs, while itraconazole, an antifungal medicine, has shown positive results in recent years.
CASE SUMMARY In the present study, itraconazole was applied to treat two IH cases. The therapeutic course lasted 80-90 d, during which the visible lesion faded by more than 90%. Moreover, no obvious side effects were reported, and the compliance of the baby and parents was desirable.
CONCLUSION Although these outcomes further support itraconazole as an effective therapeutic choice for IHs, large-scale clinical and basic studies are still warranted to improve further treatment.
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Affiliation(s)
- Zhe Liu
- Department of Dermatology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Sha Lv
- Department of Dermatology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Shuang Wang
- Department of Dermatology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Sheng-Ming Qu
- Department of Dermatology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Gui-Yun Zhang
- Department of Dermatology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Yi-Tong Lin
- Department of Dermatology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Lei Yang
- Department of Dermatology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
| | - Fu-Qiu Li
- Department of Dermatology, The Second Hospital of Jilin University, Changchun 130041, Jilin Province, China
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Zhang J, Ye Z, Tan L, Luo J. Giant Hepatic Hemangioma Regressed Significantly Without Surgical Management: A Case Report and Literature Review. Front Med (Lausanne) 2021; 8:712324. [PMID: 34490301 PMCID: PMC8416894 DOI: 10.3389/fmed.2021.712324] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 07/16/2021] [Indexed: 11/13/2022] Open
Abstract
Hepatic hemangioma (HH) is a congenital vascular anomaly comprising networks of abnormal blood and/or lymphatic vessels with endothelial cell proliferation. Their pathophysiology is not fully understood, and no specific drug is available to treat them. Conservative management, which limits observation, is preferred for most patients. A HH larger than 4 cm is considered a giant HH that may be treated using surgery ranging from embolization to hepatic resection or liver transplantation. Here, we describe a case with multiple and giant HHs that regressed significantly after treatment with azithromycin (AZM). A systematic literature review of HH and the effects of AZM on angiogenesis was then conducted.
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Affiliation(s)
- Jingcong Zhang
- Department of Internal Medicine, Medical Intensive Care Unit and Division of Respiratory Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zuyang Ye
- Department of Nephrology, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
| | - Lei Tan
- Department of Medical Ultrasonic, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Jinmei Luo
- Department of Internal Medicine, Medical Intensive Care Unit and Division of Respiratory Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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