Exploring the Potential of Dendrimers in Skin Drug Delivery: Applications and Advances

Dendrimers (DDs) have become a pioneering tool in dermatological nanomedicine thanks to their branched nanostructure, high precision, and multifunctional nature. The purpose of this review is to highlight the revolutionary potential of DDs regarding the primary barrier for skin drug delivery - the stratum corneum. The enhanced solubility, controlled drug release, and facilitated drug penetration achieved by the customized dendrimer architecture are described in terms of diffusion, degradation, and stimuli-responsive mechanisms. The latest achievements are critically assessed through the topical approaches for psoriasis, wound healing, and skin cancer treatment, as well as transdermal delivery for systemic vaccines and gene therapy. The essential aspect of surface engineering is also analyzed in terms of its dual-edged features-chemical functionalization optimizes skin affinity and therapeutic specificity while addressing toxicological issues. Quantitative data from the literature have been provided to support the benefits, such as a 4.5-fold increase in the transdermal flux of indomethacin using PAMAM G4 and 2.7-fold and 2.5-fold increases in the bioavailability of ketoprofen and diflunisal, respectively. Moreover, in the studies applying dendrimers combined with sonophoresis, the permeability results demonstrated a noticeable trend - e.g., 935.21 μg/cm2 versus 56.69 μg/cm2 permeation, which indicates the possibility of synergism with physical enhancement methods Moreover, in the studies applying dendrimers combined with sonophoresis, the permeability results demonstrated a noticeable trend - e.g., 935.21 μg/cm2 versus 56.69 μg/cm2 permeation, which indicates the possibility of synergism with physical enhancement methods. To ensure successful transfer to clinics, an increased focus on long-term safety, synthesis scalability, and reproducibility is needed. This article provides an in-depth, objective, and holistic assessment of dendrimers as a versatile, continually expanding and improving toolkit for targeted skin therapies.