Advanced nanocarrier- and microneedle-based transdermal drug delivery strategies for skin diseases treatment

Abstract

Skin diseases are the fourth leading cause of nonfatal and chronic skin diseases, acting as a global burden and affecting the world economy. Skin diseases severely impact the patients' quality of life and have influenced their physical and mental state. Treatment of these skin disorders with conventional methods shows a lack of therapeutic efficacy, long treatment duration, recurrence of the condition, and systemic side effects due to improper drug delivery. However, these pitfalls can be overcome with the applications of advanced nanocarrier- and microneedle (MN)-based transdermal drug delivery strategies that provide efficient site-specific drug delivery at the target site. These advanced transdermal drug delivery strategies can be more effective than other drug administration routes by avoiding first-pass metabolism, enhancing the drug concentration in local skin lesions, and reducing systemic toxicity. Compared with traditional transdermal delivery methods, nanocarrier- or MN-based drug delivery systems are painless, noninvasive, or minimum-invasive and require no expensive equipment. More importantly, they can introduce more advanced functions, including increased skin penetration efficiency, controlled drug release rates, enhanced targeting abilities, and theranostic functions. Here, the emergence of versatile advanced transdermal drug delivery systems for the transdermal delivery of various drugs is reviewed, focusing on the design principles, advantages, and considerations of nanocarrier- and MN-based transdermal drug delivery strategies and their applications in treating diverse skin diseases, including psoriasis, dermatitis, melanoma, and other skin diseases. Moreover, the prospects and challenges of advanced transdermal delivery strategies for treating dermatological disorders are summarized.

Safety Challenges and Application Strategies for the Use of Dendrimers in Medicine

“…In addition, when treated with high concentrations of PAMAM-NH 2 dendrimers, PCNA was highly expressed in all layers of the skin, and the nuclear immune response was enhanced, thus indicating a cell proliferation disorder. Collectively, microscopic evaluations and immunohistochemical analyses showed that cationic PAMAM dendrimers readily led to significant skin toxicity and that low concentrations should be considered for practical external use [118,133].…”

Recent advances and future prospective of topical and transdermal delivery systems

“…This treatment technique has gained enormous attention from researchers owing to its various benefits, i.e., it avoids the degradation of therapeutics in the gastrointestinal tract, circumvents the first-pass metabolism in the liver (in the case of oral delivery), and prevents the invasive and painful approach via the intravenous delivery of drugs (Figure 3) (Fernando et al, 2018;Qu et al, 2022); hence, it is considered an effective approach in transdermal drug delivery. Microneedles are composed of an array of micron-sized needles that pierce the SC (10-20 um) and deliver the actives directly to the viable epidermis, bypassing the SC barrier and providing high drug bioavailability compared to Frontiers in Drug Delivery frontiersin.org creams and the transdermal patch (Figure 1) (Waghule et al, 2019;Avcil and Çelik, 2021;Ali et al, 2022;Qu et al, 2022). Due to these various advantages, microneedles and their patches have also been translated to clinical stages in the delivery of vaccines (Fernando et al, 2018); however, this strategy has some limitations, such as compatibility, loading capacity, dose restriction due to small size of microneedles, irritation, and inflammatory immune response (Avcil and Çelik, 2021).…”

Drug delivery systems for treatment of temporomandibular joint osteoarthritis

“…Transdermal drug delivery approaches can avoid first-pass metabolism, control the drug release rates over a prolonged time, and reduce the risk of systemic side effects ( Morry et al, 2015 ). Skin also acts as a reservoir, which enables the diffusion of the penetrated drugs from skin continuously for a longer period and presents an opportunity of lower frequency of administration ( Qu et al, 2022 ). As the stratum corneum (SC) layer of the skin is the capital barrier which limits the penetration of most drugs, many approaches have been adopted to disrupt the SC layer and increase skin permeability, including physical enhancers (iontophoresis, electroporation, sonophoresis, and microneedles), chemical enhancers (alcohol and peptide), and delivery vehicles (spherical nucleic acid and lipoplexes) ( Ita 2017 ; Phatale et al, 2022 ; Qu et al, 2022 ).…”

“…Skin also acts as a reservoir, which enables the diffusion of the penetrated drugs from skin continuously for a longer period and presents an opportunity of lower frequency of administration ( Qu et al, 2022 ). As the stratum corneum (SC) layer of the skin is the capital barrier which limits the penetration of most drugs, many approaches have been adopted to disrupt the SC layer and increase skin permeability, including physical enhancers (iontophoresis, electroporation, sonophoresis, and microneedles), chemical enhancers (alcohol and peptide), and delivery vehicles (spherical nucleic acid and lipoplexes) ( Ita 2017 ; Phatale et al, 2022 ; Qu et al, 2022 ). It is reported that transdermal drug delivery approaches enable topical drug delivery to the periarticular tissues of TMJs, which offer a painless and convenient platform to treat TMJOA-associated conditions ( Figure 2 and Table 2 ).…”