Pramlintide an Adjunct to Insulin Therapy: Challenges and Recent Progress in Delivery

Abstract

Dysregulation of various glucoregulatory hormones lead to failure of insulin monotherapy in patients with diabetes mellitus due to various reasons, including severe hypoglycaemia, glycaemic hypervariability, and an increased risk of microvascular complications. However, pramlintide an adjunct to insulin therapy, enhances glucagon suppression and thereby offers improved glycaemic control. Clinical studies have shown that pramlintide improves glycaemic control, reduces postprandial glucose excursions, and promotes weight loss in patients with type 1 and type 2 diabetes. Although clinical benefits of pramlintide are well reported, there still exists a high patient resistance for the therapy as separate injections for pramlintide and insulin are required to be administered. While marketed insulin formulations generally demonstrate a peak action in 60-90 min, pramlintide elicits its peak concentration at around 20-30 min after administration. Thus, owing to the significant differences in pharmacokinetics of exogenously administered pramlintide and insulin, the therapy fails to elicit its action otherwise produced by the endogenous hormones. Hence, strategies such as delaying the release of pramlintide by using inorganic polymers like silica, synthetic polymers like polycaprolactone and lipids have been employed. Also, approaches like noncovalent conjugation, polyelectrolyte complexation and use of amphiphilic excipients for codelivery of insulin and pramlintide have been explored to address the issues with pramlintide delivery and improve patient adherence to the therapy. This approach may usher a new era of diabetes management, offering patients multiple options to tailor their treatment and improve their quality of life. Significance StatementTo our knowledge, this is the first report that summarizes various challenges in insulin and pramlintide co-delivery and strategies to overcome them. The paper also provides deeper insights into various novel formulation strategies for pramlintide that could further broaden the readers understanding of peptide co-delivery.

Special Section on Nanotechnology-Based Delivery Strategies for Protein and Peptide Therapeutics—Editorial

“…The minireview presents a detailed discussion on the formation of SA and the design and development of drug delivery systems based on SA and critically analyzes the advantages and disadvantages of SA, particularly for the treatment of cancer (Das et al, 2023). The fourth paper in this special section, by Kommera et al (2023), exposes the reader to the different delivery strategies for peptide-and protein-based therapeutics by describing the challenges associated with effective delivery of the antidiabetic peptide pramlintide, a chimeric peptide and a synthetic version of amylin, alone or in combination with insulin. The paper sheds light on the use of inorganic systems, polymeric and lipidic systems, polymer conjugates, and noncovalent modification strategy for delivery of pramlintide alone as well as when coformulated with insulin (Kommera et al, 2023).…”

“…The fourth paper in this special section, by Kommera et al (2023), exposes the reader to the different delivery strategies for peptide-and protein-based therapeutics by describing the challenges associated with effective delivery of the antidiabetic peptide pramlintide, a chimeric peptide and a synthetic version of amylin, alone or in combination with insulin. The paper sheds light on the use of inorganic systems, polymeric and lipidic systems, polymer conjugates, and noncovalent modification strategy for delivery of pramlintide alone as well as when coformulated with insulin (Kommera et al, 2023). The last paper of the session, by Nagar et al (2023), focuses on the huge library of promising proteinbased nanocarriers and nanotherapeutics explored for infectious and inflammatory ailments, with particular emphasis on proteins nanoparticles of human and pathogenic origin, with reference to their advantages, pharmacokinetic parameters, and the current bottlenecks in the development of protein-based nanotherapeutic interventions (Nagar et al, 2023).…”