Core-shell structure alginate-PLGA/PLLA microparticles as a novel drug delivery system for water soluble drugs
Recent focus on particle based drug delivery systems, necessitates improved drug loading and sustainable release for water soluble drugs. Biodegradable polyesters, such as poly (lactide-co-glycolide) (PLGA) and poly (L-lactide) (PLLA), are well studied but are insufficient in terms of encapsulation...
Saved in:
Main Author: | |
---|---|
Other Authors: | |
Format: | Theses and Dissertations |
Language: | English |
Published: |
2015
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/62178 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Nanyang Technological University |
Language: | English |
Summary: | Recent focus on particle based drug delivery systems, necessitates improved drug loading and sustainable release for water soluble drugs. Biodegradable polyesters, such as poly (lactide-co-glycolide) (PLGA) and poly (L-lactide) (PLLA), are well studied but are insufficient in terms of encapsulation efficiency for water soluble drugs and providing a stable environment for macromolecule encapsulation. Even though hydrogels could allow for higher encapsulation efficiency of water soluble drugs, they are inadequate in terms of sustained and controlled release. Hence, the aim of this study was to develop a particulate drug delivery system, with drug-loaded alginate hydrogel core, encapsulated by a hydrophobic polyester shell. This is hoped that this would improve the loading of water soluble drugs, while allowing for the release behavior to be governed by the core-shell geometry of the particulates formed. In addition, the hydrogel core is also expected to perform as a stable and friendly environment for protein encapsulation. In this work, a one-step fabrication method of core-shell microparticles by concurrent ionotropic gelation and solvent extraction was studied. The resultant microparticles fabricated, have a core-shell structure of calcium alginate, encapsulated in a shell constructed of either PLGA or PLLA. The cross-sectional morphology of particles was established via scanning electron microscopy, Raman mapping and selective dissolution of hydrogel material. The incorporation of alginate within the microparticles was shown to improve loading efficiency of model hydrophilic drug metoclopramide (MCA). Release studies also showed that the polyesteric shell functioned as a limiting barrier in drug release from a MCA loaded drug hydrogel core. Lysozyme and bovine serum albumin released from the microparticles fabricated, show similar behavior in release controlled by the polymeric shell, and also the preservation of bioactivity and protein structure post release. It is also noted that the double emulsion based fabrication method, relies on concurrent ionotropic gelation of the alginate dissolved within the internal aqueous phase of the double emulsion to form calcium alginate; and solvent evaporation to cause precipitation of the shell polymer. It is also put forward that the oil layer of the double emulsion, consisting of a hydrophobic polymer dissolved within a volatile solvent during fabrication, act as a semi-permeable membrane during fabrication and is subject to osmotic pressure forces acting from both aqueous phases. The permeability of this oil layer, the solvent extraction and polymer precipitation rate; effects of osmotic pressure; double emulsion stability; affects the particulate fabrication in terms of the cross sectional morphology, surface morphology and also subsequently release behavior. Hence, it is hoped that this new particulate drug delivery system would be valuable in areas such as delivery of macromolecules, including peptides, proteins and vaccine antigens. Consequently, these hydrogel-core hydrophobic polymer-shell microparticles would permit the improved encapsulation and release of water soluble drugs, and provide a safe environment for loading bioactive molecules. |
---|