RESUMO
The microneedles show advantages over transdermal drug delivery systems on account of better skin permeation bypassing the stratum corneum. To increase the flux of permeation, penetration enhancement techniques like physical and chemical methods are combined with a trans-epidermal delivery system across the skin causing minimal pain. These techniques include iontophoresis, sonophoresis, and electroporation for physical enhancement of drug delivery via topical route by either disrupting the structure of the stratum corneum or by creating pores/micro-channels within the skin. The use of chemical penetrants such as ethanol, lipids, surfactants, and terpenes improves the release kinetics by mechanisms like fluidization of lipids, denaturation of proteins, etc. A combination of microneedles and these techniques show a significant increase in the permeability of drugs across the skin by 5-10 times compared to microneedles alone. This review article focuses on various advanced strategies like the use of drug-polymer complexes, application of ultrasound frequency or tolerable electric current, formation of nano-formulations, etc. with microneedle delivery for transportation of high payload of actives, macromolecules, antibodies, gene, proteins, and peptides. In the near future, microneedle systems will offer potential targeted drug delivery, self-sealable administration across the skin, and minimally invasive vaccine transportation in cancer, diabetes, Alzheimer's, and cardiovascular diseases.HighlightsPhysical penetration enhancement techniques: iontophoresis, electroporation, and sonophoresis.Chemical penetration enhancers: polymers, lipids, surfactants.Strategies to use microneedle system with penetration enhancement techniques.The significant difference in the penetration ability of high payload actives.