Thermo-Responsive Niosomal In Situ Gels for Topical Delivery of Prednisolone

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2025-04-29 DOI:10.1208/s12249-025-03105-8

Rania Hamed, Rafa Aburayya, Ahlam Zaid Alkilani, Alaa M. Hammad, Osama H. Abusara, Hadeel Abo-Zour

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Abstract

Prednisolone (PRD) is known for its anti-inflammatory effect on the skin. The study aimed to encapsulate PRD into niosomes and then load them into thermo-responsive in situ gels for skin inflammation to enhance drug stability, skin permeability, and patient compliance while minimizing systemic exposure. PRD was encapsulated into non-PEGylated and PEGylated niosomes and then loaded into thermo-responsive in situ gels. The non-PEGylated PRD niosomes exhibited a particle size (PS) of 354.3 ± 1.9 nm, a polydispersity index (PDI) of 0.3 ± 0.0, and a ζ-potential of - 19.4 ± 1.0 mV. While the PEGylated attained PS, PDI, and ζ-potential of 314.9 ± 4.2 nm, 0.1 ± 0.0, and - 34.6 ± 2.2 mV, respectively. In addition, PEGylated niosomes exhibited higher entrapment efficiency and drug loading than non-PEGylated niosomes. The loading of the non-PEGylated and PEGylated PRD niosomes into thermo-responsive in situ gel showed a phase transition (T_sol→gel) at 34.1 ± 0.4 and 33.2 ± 0.9°C, respectively. The in situ gels showed a pseudoplastic flow with viscoelastic properties. The PRD niosomes and their corresponding in situ gels were biocompatible against human gingival fibroblasts. A decrease in rat paw inflammation was observed after applying the PRD niosomal gels. Stability studies for 3 months at 4°C showed that the PEGylated PRD niosomes and their corresponding in situ gel were more stable than the non-PEGylated PRD niosomes and their corresponding in situ gel. In conclusion, PEGylated PRD niosomal in situ gel demonstrated superior stability and sustained release, making it a promising candidate for topical corticosteroid therapy.

Graphical Abstract

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局部给药强的松龙的热响应性乳质体原位凝胶

强的松龙（PRD）以其对皮肤的抗炎作用而闻名。该研究旨在将PRD包封到膜小体中，然后将其装载到皮肤炎症的热反应原位凝胶中，以增强药物稳定性、皮肤渗透性和患者依从性，同时最大限度地减少全身暴露。将PRD包被非聚乙二醇化和聚乙二醇化的乳质体中，然后装入热响应原位凝胶中。非聚乙二醇化的PRD纳米体的粒径（PS）为354.3±1.9 nm，多分散指数（PDI）为0.3±0.0，ζ电位为- 19.4±1.0 mV。而聚乙二醇化产物的PS、PDI和ζ电位分别为314.9±4.2 nm、0.1±0.0和- 34.6±2.2 mV。此外，聚乙二醇化的乳质体比非聚乙二醇化的乳质体具有更高的包裹效率和载药量。非聚乙二醇化和聚乙二醇化的PRD niosomes分别在34.1±0.4°C和33.2±0.9°C加载到热响应原位凝胶中，显示出相变（Tsol→gel）。原位凝胶表现为具有粘弹性的假塑性流动。PRD膜小体及其相应的原位凝胶与人牙龈成纤维细胞具有生物相容性。应用PRD膜体凝胶后，观察到大鼠足部炎症减轻。在4°C下进行的为期3个月的稳定性研究表明，聚乙二醇化的PRD乳小体及其相应的原位凝胶比非聚乙二醇化的PRD乳小体及其相应的原位凝胶更稳定。综上所述，聚乙二醇化的PRD乳质体原位凝胶具有优异的稳定性和缓释性，使其成为局部皮质类固醇治疗的有希望的候选物。图形抽象

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.