Hollow microparticles as superior carriers for encapsulation and delivery of biomolecules

• Main Author: Kharel, Sharad
• Other Authors: Loo Say Chye Joachim
• Format: Theses and Dissertations
• Language: English
• Published: 2018
• Subjects: DRNTU::Engineering::Materials::Biomaterials
• Online Access: http://hdl.handle.net/10356/73864
• Institution: Nanyang Technological University

Bioactive molecules like peptides and proteins have gained significant attention in the field of therapeutics due to their exquisite specificity to their targets resulting in greater effective potency, reduced therapeutic dose and side effects. However, their low systemic stability and short half-life limits their potential. To overcome these problems, biodegradable polymer microparticles composed of polyester such as PLGA have been extensively used as carriers for delivery. However, they suffer from major limitations such as incomplete release and loss in bioactivity of the encapsulated biomolecules. Therefore, the overall objective of this thesis is to develop a method to fabricate hollow microparticles through an easy one-step method and validate the hollow microparticles as superior carriers for encapsulation and delivery of biomolecules. A method was developed wherein emulsion solvent evaporation technique was modified by adding osmogen into the oil phase before emulsification to fabricate hollow microparticles. The results obtained show conclusive evidence that by simply altering the amounts of osmogen in the formulation, the shell thickness and volume space of hollow cavity could be easily controlled. This was found to be an effective means to control and fine-tune the release kinetics of biomolecules to overcome the issue of incomplete release as observed in solid microparticles. It was found that by changing the particle morphology to hollow, the accumulation of polymer degradation products could be significantly reduced. This helped in reduction of acidic microenvironment in the microparticles, which decreased polymer-biomolecule adsorption. Consequently, the release of biomolecules from the microparticles was improved over solid microparticles. Furthermore, the bioactivity of encapsulated biomolecules was also preserved better in the hollow microparticles. It was thus established that hollow microparticles are superior over solid microparticles for delivery of biomolecules.