Title:	Preparation and Characterization of Biomimetic Molecularly Imprinted Polymer for Controlled Release Drug Delivery System of Oral Insulin
Authors:	Roongnapa Srichana Pijush Kumar Paul Faculty of Pharmaceutical Sciences (Pharmaceutical Chemistry) คณะเภสัชศาสตร์ ภาควิชาเภสัชเคมี
Keywords:	Insulin Controlled release;Controlled release preparations;Drug delivery systems
Issue Date:	2017
Publisher:	Prince of Songkla University
Abstract(Thai):	The synthesis and characterization of biomimetic molecularly imprinted nanoparticle polymers (MIPs) via chemical patterning was studied using two sources of insulin for determination of effective selectivity. Dynamic laser light scattering (DLS) measurements revealed that the zeta potentials of the nanoparticles were size-dependent and were between -20 to -33 mV with an average particle size in the range of 200 to 220 nm. This was confirmed by transmission electron microscopy (TEM) observations and atomic force microscopy (AFM) images which showed the template pattern-dependencies and confirmed that the accommodated bionanomaterial was inside the nanopores with a size of 2×25×25 nm (height> length width). This was also related to the geometry of the insulin. Analysis by the Brunauer-Emmett- Teller (BET) demonstrated the presence of mesopores of around 20 nm as well. AFM images showed the immobilization of isolated amino acids assembled on the insulin surface within the internal particle that tuned the scattering as determined by the Raman intensities and their expected involvement in the viability of the geometry. All the MIPS exhibited a much higher affinity towards the insulin and the bound islets with different adsorption kinetics due to two equilibria. There was a significantly higher partition behavior at a pH of 7.4 in a sustained-release manner for 12 h, compared to the pH of 1.2. In vitro-in vivo correlations in diabetic Wistar rats showed that the measured rate limitation was the same within 2 h, as the result of the small- molecule ligands that were associated at the outer layer and presented a barrier for the diffusion of both types of oral insulin across the GI resulting in a significant hypoglycemic effect for up to 24 h. Thus, the MIPS biomimetic receptors were employed for analysis of functional and directional-molecular interactions in the nanoscale material for biocompatibility and showed a potential for designing switching formulations for the delivery of oral insulin. Further investigation in the effects of interaction of MIPS nanoparticles with insulin on intestinal transport was carried out in animal models. Fluorescence spectroscopic analysis and desorption test revealed the better interaction of MIP with insulin compared to the control polymer (NIPs). Immunohistochemistry study indicated that the insulin remained active after the oral administration. Immunofluorescence staining results showed the in vivo absorption of MIPs nanoparticles and insulin. The fluorescent intensity of rhodamine labeled insulin for MIPs was significantly greater (P< 0.0001) than that of NIPs. Ultrastructural examination of intestinal segments by electron microscope displayed the uptake of insulin loaded MIPS nanoparticles via transcellular pathway by enterocytes whereas; no insulin was observed in the paracellular space. Histopathological observation exhibited no obvious toxic effect after orally treated with MIPs loaded insulin (100 mg/kg) daily for 14 days compared to control group. The above results suggest that biomimetic-insulin MIPs nanoparticles could be an effective tool for oral insulin delivery. The approach of imprinting for oral delivery application has potential to enhance bioavailability.
Description:	Thesis (Ph.D., Pharmaceutical Sciences)--Prince of Songkla University, 2017
URI:	http://kb.psu.ac.th/psukb/handle/2016/12189
Appears in Collections:	565 Thesis

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