The skin is the largest organ of the human body and acts as a major protective barrier against external agents. However, the highly organized stratum corneum limits the effective delivery of many therapeutic compounds, especially hydrophilic and high-molecular-weight drugs. Conventional topical formulations often exhibit poor permeability, low bioavailability, and limited targeting efficiency. This review discusses recent advances in nanotechnology-based drug delivery systems, including bio-based, biodegradable, and biocompatible polymeric nanocarriers for dermal and transdermal applications, with particular emphasis on vesicular, polymeric, and hybrid nanosystems. Nanocarriers such as liposomes, ethosomes, transfersomes, polymeric nanoparticles, micelles, nanogels, and lipid–polymer hybrid systems have demonstrated improved drug solubility, stability, controlled release, and skin permeation for localized (dermal) delivery compared with conventional formulations. In addition, biodegradable polymeric materials enhance dermal deposition and prolong drug retention, leading to improved therapeutic efficacy. These nanosystems can facilitate enhanced transdermal drug transport under optimized conditions; however, the extent of systemic delivery varies widely depending on drug physicochemical properties, formulation characteristics, and application conditions. Drug transport may occur through intercellular, transcellular, and follicular pathways, resulting in enhanced bioavailability and site-specific delivery. Claims regarding transdermal (systemic) absorption are restricted to cases supported by in vivo or clinical evidence. Furthermore, combining nanocarriers with microneedles and stimuli-responsive platforms has expanded the potential for controlled and on-demand transdermal delivery. Recent preclinical and clinical studies have reported that nanocarrier-based methotrexate gels reduced PASI-like scores by over 70% in psoriatic models, while oleic acid vesicle formulations achieved more than 95% cure rates in rodent models of tinea corporis. Despite these advances, challenges related to large-scale production, stability, regulatory approval, and clinical translation remain significant. Future developments integrating smart nanocarriers, bio-based polymeric biomaterials, wearable technologies, and AI-assisted design may improve personalized dermatological therapies. These innovations in nanocarrier drug delivery are accelerating the translation of advanced therapies to the clinic, promising safer, more effective and personalized dermatological treatments.

Liposome–cell membrane interactions that initiate a membrane fusion may lead to direct drug cytoplasmic delivery. This study shows that the fusion of liposomes incorporating α-linolenic acid occurs as a site-restricted event at the cell membrane.

Sulfadiazine has gained renewed interest as a repurposed anticancer agent owing to its ability to inhibit folate-dependent metabolic pathways and disrupt tumor cell proliferation. However, its therapeutic potential is hindered by poor aqueous solubility, short gastric residence time, and limited absorption from the gastrointestinal tract. This study aimed to develop a gastro-retentive floating microsponge system to enhance gastric retention and sustain release of sulfadiazine for improved absorption. Microsponges were prepared using the quasi-emulsion solvent diffusion method with Eudragit RS 100 as the polymer matrix. Three formulations (F-1, F-2, F-3) were evaluated for production yield, drug content, entrapment efficiency, floating behavior, in-vitro drug release, surface morphology, thermal characteristics, and short-term stability. All formulations appeared as white, free-flowing microsponge powders with high production yields (91.11–97.72%). Entrapment efficiency ranged from 57.65% to 80.14%, increasing with polymer concentration. All formulations remained buoyant for more than 12 hours, confirming effective floating behavior. SEM analysis revealed spherical, porous structures, while DSC thermograms indicated reduced crystallinity of the encapsulated drug. In-vitro drug release demonstrated sustained release over 8 hours, with F-1 showing the fastest release and F-2 the most controlled profile. Stability studies showed no changes in appearance and minimal variation in drug content over three months. The results suggest that sulfadiazine-loaded gastric floating microsponges can enhance gastric residence, support sustained delivery, and improve the therapeutic potential of sulfadiazine as a repurposed anticancer agent.