Yadav Akshay Ramchandra, Shinde Shital Aniket, Sutar Shubhangi B, Arvindekar Snehal Aditya, Syukri Dwi Marlina
Krishna College of Pharmacy, Karad, Maharashtra 415539, India.
Ashokrao Mane College of Pharmacy, Peth-Vadgaon, Kolhapur 416 112, India.
Curr Opin Pharmacol. 2025 Aug;83:102540. doi: 10.1016/j.coph.2025.102540. Epub 2025 May 21.
Chronic skin infections, such as those caused by bacteria, viruses, and fungi compromise the skin's physical barrier, allowing microbial incursion, biofilm formation, and weakened immune response. This microbial assault disrupts skin hydration, and pH and induces inflammation, making it difficult for drug formulations to penetrate and manage the infection effectively. Traditional therapeutic strategies face hurdles like poor drug retention, systemic side effects, and antimicrobial resistance. Transdermal drug delivery systems (TDDS), on the other hand, offer localized and regulated drug release, decreasing systemic toxicity and improving bioavailability. However, physiological barriers, primarily the stratum corneum, limit the drug's capability to penetrate the deeper layers of the skin and necessitate the usage of permeation enhancers and advanced formulation techniques. Physicochemical barriers of the drug, including high molecular weight, lipophilicity, and solubility, also hamper transdermal drug absorption. Additionally, issues related to drug stability, release kinetics, and adhesive matrices affect drug retention, controlled release, and therapeutic efficacy in the infected skin, which might be compromised due to ulceration, hyperkeratosis, or excessive irritation. Novel strategies such as nanocarrier-based TDDS including liposomes, nanoparticles, and microneedles potentially improve drug permeation and bioavailability while treating chronic skin infections. Nevertheless, the challenges remain in adjusting the compatibility of the drug formulations with the infected skin, while maintaining its effectiveness. This review is a comprehensive look at the physiological and formulation challenges in TDDS for managing chronic skin infections. More real-world evidence is required to further refine TDDS formulations for improved permeation, stability, and clinical efficacy against chronic skin infections.
慢性皮肤感染，如由细菌、病毒和真菌引起的感染，会破坏皮肤的物理屏障，使微生物得以侵入、形成生物膜并削弱免疫反应。这种微生物攻击会扰乱皮肤的水合作用和pH值，并引发炎症，使得药物制剂难以有效渗透和控制感染。传统治疗策略面临着诸如药物滞留性差、全身副作用和抗微生物耐药性等障碍。另一方面，透皮给药系统（TDDS）可实现局部和可控的药物释放，降低全身毒性并提高生物利用度。然而，生理屏障，主要是角质层，限制了药物穿透皮肤深层的能力，因此需要使用渗透促进剂和先进的制剂技术。药物的物理化学屏障，包括高分子量、亲脂性和溶解性，也会阻碍透皮药物吸收。此外，与药物稳定性、释放动力学和黏附基质相关的问题会影响药物在感染皮肤中的滞留、控释和治疗效果，而由于溃疡、角化过度或过度刺激，这些效果可能会受到损害。基于纳米载体的TDDS等新策略，包括脂质体、纳米颗粒和微针，在治疗慢性皮肤感染时可能会提高药物渗透性和生物利用度。尽管如此，在调整药物制剂与感染皮肤的相容性并保持其有效性方面，挑战依然存在。本综述全面探讨了TDDS在管理慢性皮肤感染方面的生理和制剂挑战。需要更多实际证据来进一步优化TDDS制剂，以提高其对慢性皮肤感染的渗透性、稳定性和临床疗效。
