NEXT-GENERATION ADVANCEMENTS IN POLYMERIC MICRONEEDLES AND NANO CARRIER-MEDIATED TRANSDERMAL DRUG DELIVERY SYSTEMS

Transdermal drug delivery systems (TDDS) provide several advantages over conventional oral and parenteral routes, including avoidance of gastrointestinal degradation and hepatic first-pass metabolism, improved patient compliance, and controlled drug delivery. However, the stratum corneum acts as a major barrier, limiting the passive transport of hydrophilic and high-molecular-weight therapeutic agents. This review focuses on recent advances in polymeric microneedles and nanocarrier-mediated transdermal drug delivery systems developed to overcome these skin-permeation limitations. Literature from PubMed and Scopus was reviewed with emphasis on microneedle classification, polymeric biomaterials, nanocarrier systems, drug-loading capacity, permeation mechanisms, safety, and clinical translation. Polymeric microneedles, including solid, coated, dissolving, hydrogel-forming, and hollow systems, enable controlled and minimally painful delivery by creating temporary microchannels through the stratum corneum. Nanocarriers such as liposomes, ethosomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and inorganic nanoparticles further enhance dermal and transdermal drug transport through lipid fluidization, follicular pathways, and controlled drug deposition. The integration of these technologies provides promising opportunities for delivering macromolecules, vaccines, and localized therapeutics. Future developments involving stimuli-responsive systems, wearable biosensors, artificial intelligence, microfluidics, and personalized manufacturing may further enhance transdermal therapy. Despite challenges related to manufacturing scalability, regulatory standardization, and long-term biocompatibility, advanced microneedle and nanocarrier platforms have considerable potential for clinical translation and personalized drug delivery. Background: Traditional transdermal drug delivery systems (TDDS) provide a non-invasive, patient-compliant route that avoids gastrointestinal degradation and hepatic first-pass metabolism. However, the impermeable lipid matrix of the stratum corneum strictly limits the passive transport of molecules to those possessing specific hydrophobic profiles and low molecular weights. Objective: This comprehensive review examines contemporary physical and chemical breakthrough technologies, with specific focus on polymeric microneedles (MNs) and nanocarrier-facilitated delivery platforms engineered to overcome these macro-molecular transport constraints. Methodology: A systematic screening of literature from the PubMed and Scopus databases (spanning foundational models through 2026) was conducted to evaluate the mechanical structural properties, biopolymer selections, and systemic pharmacokinetics of advanced skin-permeation platforms. Results: Polymeric microneedles (dissolving, hydrogel-forming, and stimuli-responsive types) demonstrate precise disruption of the stratum corneum without contacting dermally located pain-sensitive nerve endings. Concurrently, lipidic, polymeric, and inorganic nanocarriers capitalize on hair follicles and transient lipid fluidization to deposit high-molecular-weight biologics, vaccines, and localized therapeutics. Conclusion: Combining active mechanical microneedles with target-specific nanocarriers represents the vanguard of modern personalized diagnostics and therapeutics, bridging laboratory innovation with clinical scale-up paradigms.