Microneedle-Mediated Transdermal Delivery of Biopharmaceuticals

Abstract

Transdermal delivery provides numerous benefits over conventional routes of administration. However, this strategy is generally limited to a few molecules with specific physicochemical properties (low molecular weight, high potency, and moderate lipophilicity) due to the barrier function of the stratum corneum layer. Researchers have developed several physical enhancement techniques to expand the applications of the transdermal field; among these, microneedle technology has recently emerged as a promising platform to deliver therapeutic agents of any size into and across the skin. Typically, hydrophilic biomolecules cannot penetrate the skin by passive diffusion. Microneedle insertion disrupts skin integrity and compromises its protective function, thus creating pathways (microchannels) for enhanced permeation of macromolecules. Microneedles not only improve stability but also enhance skin delivery of various biomolecules. Academic institutions and industrial companies have invested substantial resources in the development of microneedle systems for biopharmaceutical delivery. This review article summarizes the most recent research to provide a comprehensive discussion about microneedle-mediated delivery of macromolecules, covering various topics from the introduction of the skin, transdermal delivery, microneedles, and biopharmaceuticals (current status, conventional administration, and stability issues), to different microneedle types, clinical trials, safety and acceptability of microneedles, manufacturing and regulatory issues, and the future of microneedle technology.

Transdermal Drug Delivery System: Current Status and Clinical Application of Microneedles

“…In various clinical application scenarios, researchers can endow polymer materials with controllable release characteristics by adjusting their concentration, molecular weight, cross-linking density, and charge characteristics. Moreover, polymers can be mixed with different types of substances, such as drugs, nanoparticles, chemicals, and biologics, to form preproduction solutions for microneedles. ,− As shown in Figure A, Lin et al developed a post-treatment method using glutaraldehyde-based cross-linking and water vapor annealing to enhance the formation of silk fibroin (SF) molecular networks and improve the mechanical strength of SF microneedles. The combination of chemical and physical treatment has resulted in internal SF microneedles with increased mechanical strength, while the external SF layer allows for controlled drug loading and release .…”

Transdermal drug delivery via microneedles for musculoskeletal systems

“…Some widely accepted scales such as the visual analog scale (VAS) are available for assessing the pain level of MNs. 195 Notably, it is considered that length contributes a greater value to pain level compared to needle density and number. 196 Though common MNs cause negligible pain in some clinical trials, 195 MNs used in the MSK system are expected to have longer needle bodies, allowing closer access to the lesion site.…”

“…195 Notably, it is considered that length contributes a greater value to pain level compared to needle density and number. 196 Though common MNs cause negligible pain in some clinical trials, 195 MNs used in the MSK system are expected to have longer needle bodies, allowing closer access to the lesion site. Thus, further investigation of the relationship between pain and MNs parameters is necessary for the clinical translation of MNs in the MSK system.…”

Recent Advances in Formulations for Long-Acting Delivery of Therapeutic Peptides

“…On the other hand, there is a heightened interest for less invasive approaches of administering peptides due to the probable stress and phobia of patients caused by invasive approaches such as SC injection that can affect patient compliancy. Some examples of recent innovations in peptide delivery are pulmonary administration (e.g., inhalable formulations), microimplantable pumps, and transdermal delivery formulations such as microneedle patches. − …”