title: Doxycycline delivery from PLGA microspheres prepared by a modified solvent removal method.
abstract: We report on the development of a modified solvent removal method for the encapsulation of hydrophilic drugs within poly(lactic-co-glycolic acid) (PLGA). Using a water/oil/oil double emulsion, hydrophilic doxycycline was encapsulated within PLGA spheres with particle diameters ranging from approximately 600 nm to 19 µm. Encapsulation efficiencies of up to 74% were achieved for theoretical loadings from 1% to 10% (w/w), with biphasic release over 85 days with nearly complete release at the end of this time course. About 1% salt was added to the formulations to examine its effects on doxycycline release; salt modulated release only by increasing the magnitude of initial release without altering kinetics. Fourier transform infrared spectroscopy indicated no characteristic differences between doxycycline-loaded and control spheres. Differential scanning calorimetry and X-ray diffraction suggest that there may be a molecular dispersion of the doxycycline within the spheres and the doxycycline may be in an amorphous state, which could explain the slow, prolonged release of the drug.
authors.affiliation: Department of Molecular Pharmacology, Physiology, and Biotechnology, Center for Biomedical Engineering, Center for Biomedical Engineering, Brown University, Providence, RI 02912, USA.
authors.forename: Roshni S
authors.initials: RS
authors.lastname: Patel
authors.forename: Daniel Y
authors.initials: DY
authors.lastname: Cho
authors.forename: Cheng
authors.initials: C
authors.lastname: Tian
authors.forename: Amy
authors.initials: A
authors.lastname: Chang
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Estrellas
authors.forename: Danya
authors.initials: D
authors.lastname: Lavin
authors.forename: Stacia
authors.initials: S
authors.lastname: Furtado
authors.forename: Edith
authors.initials: E
authors.lastname: Mathiowitz
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004318:Doxycycline / Q000008:administration & dosage*; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D004655:Emulsions; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D054118:Nanospheres / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004655:Emulsions; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004318:Doxycycline