Ivana Jovanovic MT.pdf (7089 KB) - Institut tehničkih nauka SANU

Abstract
A considerable care is currently paid worldwide to the development of biodegradable
microspheres as systems for controlled release of medicaments. The major disadvantage of traditional
medicaments administration method is the need for frequent dosage repetition. Encapsulation has been
proven to be an effective vehicle for the controlled delivery of various medicaments. The encapsulation
efficiency and release kinetics of the medicaments have been found to depend upon the size of the
microspheres synthesized. Biodegradable micro- and nanospheres made of poly-l-lactide (PLLA) and
poly-dl-lactide (PDLLA) are very potent drug or antigen delivery systems with inherent potential for
controlled drug delivery and drug and antigen targeting.
The objective of this thesis was to formulate empty and composite microspheres from PLLA and
PDLLA by modified precipitation method. Biodegradable microspheres such as those made of poly-dllactide
(PDLLA) are widely investigated delivery systems for proteins. This study investigated the effects
of some process variables on the morphology and size distribution of PLLA and PDLLA microspheres
prepared by precipitation method. Preparation conditions were then optimized to obtain the smallest
protein-loaded spheres. PDLLA microspheres can protect proteins against biological inactivation and can
release them at specific moments during the prolonged period of time. For the purpose of this paper,
bovine serum albumin (BSA) and horseradish peroxidase (HRP) were used as the model proteins, as they
were incorporated into PDLLA spheres. The aim of this study was to optimize experimental conditions in
order to produce composite microspheres with the best properties for controlled and sustained delivery of
proteins (HRP and BSA). The ability to control size of spheres should facilitate investigations of their
scope for drug delivery. For this purpose, the following parameters were varied: co-solvent (methanol or
ethanol), the concentration of stabilizer polyvinyl alcohol (PVA), chloroform-to-water ratio as well as the
speed and time of homogenization. The average size and morphology of PLLA, PDLLA and composite
microspheres (PDLLA+BSA and PDLLA+HRP) vary substantially if these preparation conditions are
changed. Scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetery
(DSC), infrared spectroscopy (IR), electrophoresis and stereological analysis were used to characterize
the particles.