*Article* **Injectable Biodegradable Silica Depot: Two Months of Sustained Release of the Blood Glucose Lowering Peptide, Pramlintide**

**Puneet Tyagi 1,\*, Mika Koskinen <sup>2</sup> , Jari Mikkola <sup>2</sup> , Sanjay Sarkhel <sup>2</sup> , Lasse Leino <sup>2</sup> , Asha Seth <sup>3</sup> , Shimona Madalli <sup>3</sup> , Sarah Will <sup>4</sup> , Victor G. Howard <sup>4</sup> , Helen Brant <sup>5</sup> and Dominic Corkill <sup>6</sup>**


**Abstract:** Diabetes mellitus is a major healthcare challenge. Pramlintide, a peptide analogue of the hormone amylin, is currently used as an adjunct with insulin for patients who fail to achieve glycemic control with only insulin therapy. However, hypoglycemia is the dominant risk factor associated with such approaches and careful dosing of both drugs is needed. To mitigate this risk factor and compliance issues related to multiple dosing of different drugs, sustained delivery of Pramlintide from silica depot administered subcutaneously (SC) was investigated in a rat model. The pramlintide-silica microparticle hydrogel depot was formulated by spray drying of silica sol-gels. In vitro dissolution tests revealed an initial burst of pramlintide followed by controlled release due to the dissolution of the silica matrix. At higher dosing, pramlintide released from subcutaneously administered silica depot in rats showed a steady concentration of 500 pM in serum for 60 days. Released pramlintide retained its pharmacological activity in vivo, as evidenced by loss of weight. The biodegradable silica matrix offers a sustained release of pramlintide for at least two months in the rat model and shows potential for clinical applications.

**Keywords:** long acting; sustained delivery; biologics; silica microparticles
