Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.

Over the past few decades, advances in hydrogel technologies have spurred development in many biomedical applications including controlled drug delivery. Many novel hydrogel-based delivery matrices have been designed and fabricated to fulfill the ever-increasing needs of the pharmaceutical and medical fields. Mathematical modeling plays an important role in facilitating hydrogel network design by identifying key parameters and molecule release mechanisms. The objective of this article is to review the fundamentals and recent advances in hydrogel network design as well as mathematical modeling approaches related to controlled molecule release from hydrogels. In the first section, the niche roles of hydrogels in controlled release, molecule release mechanisms, and hydrogel design criteria for controlled release applications are discussed. Novel hydrogel systems for drug delivery including biodegradable, smart, and biomimetic hydrogels are reviewed in the second section. Several mechanisms have been elucidated to describe molecule release from polymer hydrogel systems including diffusion, swelling, and chemically-controlled release. The focus of the final part of this article is discussion of emerging hydrogel delivery systems and challenges associated with modeling the performance of these devices.