Basal level insulin delivery: In vitro release, stability, biocompatibility, and in vivo absorption from thermosensitive triblock copolymers

• Published in: Journal of pharmaceutical sciences 2011-11, Vol.100 (11), p.4790-4803
• Main Authors: Al‐Tahami, Khaled, Oak, Mayura, Mandke, Rhishikesh, Singh, Jagdish
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biocompatibility; Biocompatible Materials; Biological and medical sciences; Blood Glucose - analysis; Calorimetry (DSC); Calorimetry, Differential Scanning; Circular Dichroism; conformational and chemical stability; Controlled release; Diabetes Mellitus, Experimental - drug therapy; Drug Delivery Systems; Drug Stability; General pharmacology; in vitro release; In Vitro Techniques; in vitrorelease; in vivo absorption; in vivoabsorption; insulin; Insulin - administration & dosage; Insulin - therapeutic use; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Protein Delivery; Rats; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Streptozocin; thermosensitive; triblock copolymer
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.22685

The major goal of this study was to develop the biodegradable and biocompatible thermosensitive polylactic acid–polyethylene glycol–polylactic acid triblock copolymer‐based delivery systems for controlled release of basal level insulin for a longer duration after single subcutaneous injection. Insulin was dispersed into aqueous copolymer solutions to prepare the delivery system. The in vitro release profile of insulin from delivery systems was studied at 37°C in phosphate‐buffered saline. Stability of released insulin was investigated using circular dichroism, differential scanning calorimetry, and matrix‐assisted laser desorption/ionization–time‐of‐flight mass spectrometry. A 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay and skin histology were used to determine the in vitro and in vivo biocompatibility of the delivery systems, respectively. Streptozotocin‐induced diabetic rat model was used to study the in vivo absorption and bioactivity of insulin. In vitro release studies indicated that the delivery systems released insulin over 3 months in structurally stable form. The delivery systems were biocompatible in vitro and in vivo. In vivo absorption and bioactivity studies demonstrated elevated insulin level and corresponding decreased blood glucose level in diabetic rats. Thus, the delivery systems released insulin at a controlled rate in vitro in conformationally and chemically stable form and in vivo in biologically active form up to 3 months. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4790–4803, 2011