Tyagi Puneet, Koskinen Mika, Mikkola Jari, Sarkhel Sanjay, Leino Lasse, Seth Asha, Madalli Shimona, Will Sarah, Howard Victor G, Brant Helen, Corkill Dominic
Dosage Form Design and Development, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD 20874, USA.
DelSiTech Ltd., PharmaCity, Itäinen Pitkäkatu 4 B, 20520 Turku, Finland.
Pharmaceutics. 2022 Mar 2;14(3):553. doi: 10.3390/pharmaceutics14030553.
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.
糖尿病是一项重大的医疗保健挑战。普兰林肽是激素胰淀素的肽类似物，目前用于仅接受胰岛素治疗却未能实现血糖控制的患者，作为胰岛素的辅助用药。然而，低血糖是与此类治疗方法相关的主要风险因素，需要谨慎确定两种药物的剂量。为降低这一风险因素以及与不同药物多次给药相关的依从性问题，在大鼠模型中研究了从皮下注射的二氧化硅储库持续递送普兰林肽的情况。普兰林肽 - 二氧化硅微粒水凝胶储库是通过溶胶 - 凝胶法喷雾干燥二氧化硅来制备的。体外溶出试验显示，普兰林肽起初有一个释放高峰，随后由于二氧化硅基质的溶解而实现控释。在较高剂量下，大鼠皮下注射二氧化硅储库释放的普兰林肽在血清中的浓度在60天内稳定维持在500 pM。释放的普兰林肽在体内保持其药理活性，体重减轻证明了这一点。可生物降解的二氧化硅基质在大鼠模型中可实现普兰林肽至少两个月的持续释放，并显示出临床应用潜力。
