Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evident from Confocal MicroRaman spectroscopy. Silica coat enhances the stability of insulin-loaded delivery vehicles. In vivo study shows that these silica coated formulations were biologically active in reducing glucose levels.
A fused lipid microstructure embedded with ferrite nanoparticles, a magnetocochleate, was prepared and used to encapsulate insulin by making use of the lipid phase transition from the fluidic lamellar phase to the gel phase at pH 2. The magnetocochleate obtained by tuning the hydrophilic headgroup hydration of phosphatidylserine in the presence of ferrite encapsulates a larger amount of insulin. Enhanced encapsulation of insulin in between the fused lipid bilayer indicates that the magnetocochleate has potential as a delivery vehicle for an active pharmaceutical incipient. In particular, protein macromolecules like insulin are target incipients, because these fused microstructures protect insulin from the action of enzymes and from pH changes, which is necessary to maintain its bioactivity. Microscopic and spectroscopic investigations of these fused microstructures were done to understand the internal microstructure and encapsulation of protein. Freeze fracture transmission electron microscopy revealed the gel-like phase of fused lipid bilayers and the presence of ferrite in magnetocochleate. Confocal micro-Raman, high performance liquid chromatography (HPLC) studies confirmed the presence of ferrite and insulin within the lipid microstructures. Differential scanning calorimetry (DSC) and Fourier transform infrared resonance (FTIR) studies substantiate the state of lipid in these fused microstructures. In vivo subcutaneous activity was studied in a rat model, and the positive result obtained there signifies the promising potential of magnetocochleates in subcutaneous delivery of macromolecules.
Proteins find a more stable environment upon encapsulation in a silica host, because of the polymeric silica frame that grows around the macromolecule and protects them from denaturation. Silica-insulin nanocomposite (SINC) and ferrite-coated SINC (FeSINC) was prepared by polyelectrolytic condensation of silica precursor on insulin and they were studied for their ability to control glucose levels. SINC was prepared by acid-base-catalyzed polymerization in the presence of insulin at room temperature by a modified Stober's process. FeSINC nanoparticles were prepared by coprecipitation of both ferric and ferrous salts on the bovine insulin loaded silica nanoparticle. The presence of ferrite coating in FeSINC was identified using a vibrating sample magnetometer and quantified from XRF study. The intermolecular interactions in these nanocomposites were studied by FTIR and Raman spectroscopy. An in vivo study indicated that FeSINC was biologically active in reducing glucose levels as compared to SINC.
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