Nanotechnology for oral delivery of insulin

• Main Author: Loh, Lyvia
• Other Authors: Subramanian Venkatraman
• Format: Final Year Project
• Language: English
• Published: 2016
• Subjects: DRNTU::Engineering
• Online Access: http://hdl.handle.net/10356/66696
• Institution: Nanyang Technological University

Diabetes Mellitus is a metabolic condition of the body, where there is a high blood glucose content, that may lead to microvascular and macrovascular complications such as retinopathy and strokes. The most widely used therapy currently is subcutaneous insulin injections that will lower blood glucose levels by stimulating glucose uptake from the blood stream by the body cells. The problem faced by this method of drug delivery is low patient compliance and the risk of hypoglycemia (low blood glucose level). A possible solution is oral delivery of insulin, which will increase patient compliance and also the oral route mimics the natural pathway of insulin delivery in the body, thus reducing the risk of hypoglycemia. However, insulin is a polypeptide that can be easily degraded in the acidic environment of the stomach. The aim of this project is to protect the contents of a capsule from the acidic stomach environment and only releasing its contents in the mildly basic environment of the intestines for absorption by coating the capsule with pH sensitive polymers. The two pH sensitive polymers selected for the study are, HP55 adopted as a pre-coat for enhanced adhesion and the main polymer coat Eudragit. This study features dip-coating of gelatin capsules encapsulating Hydrogenated Soybean Phosphatidylcholine (HSPC) with HP55 and Eudragit solutions and an in-vitro release study in pH 1.2 Simulated Gastric Fluid (SGF) and pH 6.8 Simulated Intestine Fluid (SIF). HSPC liposomes were fabricated via the solvent evaporation method and extruded through a 0.08µm filter under high pressure, liposomes were lyophilized to extend shelf-life. Scanning electron microscopy was used to observe the cross-sections and surface morphology of the coated capsules. The thicknesses of the coatings were found using software ImageJ. The optimal coating thickness is found to be at least 5 layers of coating (> 114µm) which could withstand 4 hours in SGF and to release its contents in SIF, whilst 4 coating layers (90µm) was shown to allow acid penetration and early content release. From the results obtained, it indicates that insulin protection against the gastric environment is possible. Further studies including positively charge liposomes, variation of parameters such as temperature and enzyme containing SGF and SIF could be done to determine if the conditions of release are only affected by pH.