Drug Delivery Systems Based on Hydroxyapaptite-coated Poly(lactic-co-glycolic acid) Microspheres
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1063-OO05-08
Drug Delivery Systems Based on Hydroxyapaptite-coated Poly(lactic-co-glycolic acid) Microspheres Qingguo Xu, and Jan T Czernuszka Department of Materials, University of Oxford, Parks Road, Oxford, OX1 3PH, United Kingdom ABSTRACT Negatively charged poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared by the solid-in-oil-in-water (s/o/w) method using the anionic surfactant, sodium dodecyl sulfate (SDS), and a hydrophilic antibiotic (amoxicillin) was encapsulated with an encapsulation efficiency of 40.6%. A layer of hydroxyapatite (HA) was coated on these negatively charged PLGA microspheres by a dual constant composition method in 3-6 hours. The HA-coated PLGA microspheres (HPLG) had a core-shell structure and were characterized by scanning electron microscopy, focused ion beam microscopy, energy-dispersive X-ray spectrometry, X-ray diffraction and Fourier transform infrared spectroscopy. Sustained release of amoxicillin from HPLG for at least 31 days was shown from in-vitro drug release experiments. A typical triphasic drug release profile had been observed for PLGA and HPLG microspheres. This device exhibited two desirable properties: the sustained release from PLGA and potential osteoconductivity from HA. Hence, it could have applications in delivering drugs to treat bone disorders or infections. INTRODUCTION The use of local drug delivery systems to treat bone disorders has attracted great interest because of the reduced systemic toxicities and side effects of parenteral administration [1]. Biodegradable materials have been widely used in local drug delivery systems, such as poly(lactic-co-glycolic acid) (PLGA) [2] and hydroxyapatite (HA) [3, 4]. HA and other calcium phosphates are osteoconductive and have been investigated as drug carriers, however, drug release from these ceramics are usually rapid and the sustained drug release in a controlled manner is difficult to achieve [3, 4]. PLGA can be used to encapsulate drugs at a high dose and a controlled release profile can be achieved [5, 6]. Thus a drug delivery device based on HAcoated PLGA microspheres (HPLG) has been designed to combine both osteoconductivity of HA and controlled release of PLGA. The HA coating was produced by a dual constant composition method and the drug encapsulated with a solid-in-oil-in-water (s/o/w) method [7]. The method of manufacture, properties and drug release profiles of HPLG microspheres will be presented. EXPERIMENTAL PROCEDURE Poly(lactic-co-glycolic acid) (PLGA) (50:50) with an inherent viscosity of 0.67dL/g was purchased from Birmingham Polymers Inc., USA. Amoxicillin, sodium dodecyl sulfate (SDS), dichloromethane (DCM), phosphate buffer solution (pH 7.4, 0.1M) were all obtained from Sigma (Dorset, UK). Calcium nitride, potassium nitride, potassium hydroxide, potassium dihydrogen phosphate all are supplied from BDH (Poole, UK). The negatively charged PLGA microspheres were prepared by the s/o/w methods using an anionic surfactant, SDS. 200 mg of PLGA in 2 ml of dichloromethane is mixed with 50 mg mod
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