Date of Award
Master of Science (MS)
Tao L. Lowe, Ph.D.
Isaac O. Donkor, David J. Hamilton
Diabetes mellitus is one of the major global health problems and the prevalence rate is ever increasing reaching to 48% increase by the year of 2040 causing significant economic burdens. Insulin therapy has been the mainstay of diabetes treatment since its discovery in 1922. However, insulin is an unstable peptide with a half-life of only 4-6 min which poses significant challenge in prolonging duration of action of insulin. Nevertheless, the advances in recombinant DNA technology and protein engineering have enabled the development of several long-acting insulin analogue products which show duration of action up to 42 h. However, these insulin analogues still require once- or twice-daily injections for optimal glycemic control resulting in poor compliance and adherence issues among patients. To achieve insulin release for more than one day, different injectable delivery systems including microspheres, in situ forming depots, nanoparticles and composite systems have been developed for sustained release of insulin for days to weeks in in vitro and preclinical studies. Several of these delivery systems have further advanced to clinical trials for once-weekly insulin injection to treat diabetes. Although a number of review articles have appeared in the literature to discuss the developments of long-acting insulin analogues and sustained release insulin delivery systems, none of them comprehensively cover the whole area starting all the way from prototype design and preclinical studies to clinical trials and marketed products. The scope of this review is to fill in the gap and comprehensively summarize the developments of injectable insulin analogues and delivery systems for long-term glycemic control and improved patient compliance.
Niloy, Kumar Kulldeep (0000-0001-9307-7899), "Injectable Systems for Long-Lasting Insulin Therapy" (2019). Theses and Dissertations (ETD). Paper 487. http://dx.doi.org/10.21007/etd.cghs.2019.0479.