Event Abstract Back to Event Room-temperature preparation of phosphate glass microspheres as carriers for therapeutic agents Arash Momeni1, Iain Gibson1 and Mark Filiaggi1, 2 1 Dalhousie University, Applied Oral Sciences, Canada 2 Dalhousie University, School of Biomedical Engineering, Canada Introduction: Polymeric microspheres are widely accepted as carriers for therapeutic agents (TA) due to their excellent biocompatibility and biodegradability, however they lack osteoconductivity and mechanical stiffness which glass microspheres (GMS) could offer in dental or bone-related applications. GMS are only prepared by high temperature methods (e.g. propane torch) that preclude loading of TA. Glass particles can be prepared by sol-gel methods and can be loaded by direct addition of the TA to the sol or by subsequent soaking of particles in the TA solution. However, these particles are typically irregular in shape, brittle due to porosity and display low TA encapsulation efficiency. We are describing here for the first time the feasibility of preparing spherical phosphate glass particles with excellent TA loading using polyphosphate coacervates. Materials and Methods: Sodium polyphosphate (NaPP) was prepared in-house [1] and dissolved in water (1% (g/mL)). 1M CaCl2 solution was then added to reach a Ca/P mole ratio of 0.5 forming polyphosphate coacervate [2], which was subsequently collected, freeze-dried and mixed with minocycline (antibiotic) solution (1.6±0.2% minocycline/dry coacervate (wt.)). To form the GMS, 9g of polycaprolactone (thickening agent) was dissolved in 150mL chloroform, followed by addition of 1mL of Span80 (emulsifier). To this solution, 1mL of drug-loaded coacervate was added and mixed using an overhead stirrer at 2000rpm for 90min prior to adding 300mL of acetone and mixing at 400rpm for 3hr. GMS were collected by centrifugation and washed with fresh chloroform and acetone. Cross-sectional SEM imaging of GMS was obtained after imbedding in cured resin, polishing and then applying a conductive coating. Drug loading and encapsulation efficiency were determined by measuring minocycline absorbance at 400nm. Composition was determined by energy dispersive X-ray (EDX) and inductively coupled plasma (ICP). Particle size was assessed using laser diffraction. Results and Discussion: GMS preparation is described schematically in Fig. 1. Ca2+ screens the charge on NaPP chains to yield a coacervate, a polymer-rich phase that separates form the original solution [2]. TA is mixed with the coacervate and then dispersed inside a non-solvent (Chloroform) to obtain spherical particles by surface tension, followed by water extraction (acetone addition) to transform the coacervate to glass. GMS obtained by this process were found to be highly spherical, with homogeneous composition as demonstrated by EDX mapping (Fig. 2). EDX results are in agreement with ICP data indicating a GMS Ca/P mole ratio of 0.4, similar to that observed in the precursor coacervate. A distribution of GMS sizes, between 1-200µm, was obtained that could subsequently be sieved to get to a desired bead size. Encapsulation efficiency was 62±16% (n=6) that is expectedly high as minocycline solubility in acetone and chloroform is limited, and drug loading was 1.0±0.2% (n=6). Higher drug loading is presumably feasible by introducing more minocycline to coacervate initially. Conclusion: Room-temperature preparation of therapeutically loaded phosphate glass microspheres is possible using polyphosphate coacervate precursors. Currently we are focused on minocycline elution studies and application of these microspheres in periodontitis treatment.
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