Protein Delivery
4.5 Conclusions
Significant progress has been achieved in the development of in-situ gelling ther-mosensitive polymers for biomedical and pharmaceutical applications. In order to be eligible for clinical use, hydrogels must fulfil several requirements. They must be biocompatible, protein and cell friendly, biodegradable in excretable and non-harmful products and administered in an effective and minimally invasive manner.
Importantly, they must exhibit mechanical properties and protein release behavior suitable for their specific application. Possibly, the tailorability of these properties is highly desirable. Advances in polymer chemistry has allowed the design of different topology and functionality able to accomplish many of the desired requisites. For instance, injectability can be achieved through the design of temperature-sensitive polymers displaying LCST between room and body temperature. This characteris-tic allows for minimally invasive administration, avoiding implantation by surgical intervention. As a result, the patient’s comfort and compliance are greatly enhanced.
Additionaly, self-administration of the dosage form can be applied without the use of specialized medical personnel, decreasing the burden of costly medical treatments on health care systems. Once injected, the hydrogel has to rapidly jellify and stay stable at the injection site in order to prevent premature dissolution of the gel. To this end, stabilization strategies, such as in-situ chemical crosslinking (via photopolymeriza-tion or Michael addiphotopolymeriza-tion) of thermosensitive hydrogels have been developed. The ideal release profile from hydrogels can be achieved through several mechanisms, such as physical encapsulation, chemical or affinity binding or via the use of multiple carri-ers. Biocompatibility has been implemented in several networks by hybridization of synthetic polymers with natural components. These networks are of particular impor-tance for tissue engineering application, where the gels act both as releasing matrices and as scaffolding materials for cells. Controlled biodegradation has been optimized through the use of appropriate chemistry and the insertion into the polymer backbone of (hydrolytically and enzymatically) degradable linkers. Finally, for the ultimate goal of clinical application, scale-up, stability and sterility must be taken into account. To date, although appreciable efforts have been made in the field of polymer chemistry and processing, the challenges underlying the translation from research to industrial mass production and clinical application have not been totally faced yet. It is therefore envisioned that the field of hydrogels will continue growing and exciting advances in this type of research will boost the bench-to-bedside science.
114 Handbook of Polymers for Pharmaceutical Technologies
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Vijay Kumar Thakur and Manju Kumari Thakur, Handbook of Polymers for Pharmaceutical Technologies, Volume 2 (121–150) © 2015 Scrivener Publishing LLC
*Corresponding author: [email protected]