Local Thermogelling System for Biopharmaceutical Drug Delivery

초록

The controlled local drug delivery is aimed to facilitate high site-specific concentrations of therapeutic agents with prolonged retention at lower doses with reduced systemic toxicity. In addition, therapeutic agents with a relatively short half life, such as recombinant proteins and peptides, and other biologically unstable bio-macomolecules such as nucleic acids, oligonucleotides, and siRNA can also be delivered locally with minimal loss in therapeutic activity before uptake by the target cells or tissue. For the tissue regeneration, native or genetically modified stem cells can effectively be inoculated into specific tissues. Furthermore, local drug delivery reduces patient to patient variability in drug pharmacokinetics, which is usually associated with intravenous or oral routes of drug administration. This is especially crucial for therapeutic agents with a narrow therapeutic window. The pharmaceutical and pharmacokinetic properties of proteins can be optimized by different approaches - for example, by mutagenesis, chemical modification, additives such as stabilizers and enhancers or by designing specific drug-delivery systems. In recent years, a large number of literatures have disclosed in situ forming biodegradable drug delivery systems that solidify or gel in the tissue, organ or body cavity from injectable fluids, control the release rate of drug for a certain period of time and are progressively degraded and eliminated after a certain period of application times. In situ gels can solve the problems associated with most widely used biodegradable microsphere formulations, such as the drug loss caused by low encapsulation efficiencies of microspheres, the use of harsh organic solvent and manufacturing costs increases by several processes. Definitely, the parenteral delivery including in-situ polymer gels is currently most demanding and suitable for the successful development of recombinant therapeutic proteins by stabilizing and controlling the release rate of sensitive proteins.