title: Investigation of Polycaprolactone Matrices for Intravaginal Delivery of Doxycycline.
abstract: Polycaprolactone (PCL) matrices loaded with doxycycline were produced by rapidly cooling suspensions of the drug powder in PCL solution in acetone. Drug loadings of 5%, 10%, and 15% (w/w) of the PCL content were achieved. Exposure of doxycycline powder to matrix processing conditions in the absence of PCL revealed an endothermic peak at 65°C with the main peak at 167°C, suggesting solvatomorph formation. Rapid "burst release" of 24%-32% was measured within 24 h when matrices were immersed in simulated vaginal fluid (SVF) at 37°C, because of the presence of drug at or close to the matrix surface, which is further confirmed by scanning electron microscopy. Gradual release of 66%-76% of the drug content occurred over the following 14 days. SVF containing doxycycline released from drug-loaded PCL matrices retained 81%-90% antimicrobial activity compared with the nonformulated drug. The concentrations of doxycycline predicted to be released into vaginal fluid from a PCL matrix in the form of an intravaginal ring would be sufficient to kill Neisseria gonorrhoea and many other pathogens. These results indicate that PCL may be a suitable polymer for controlled intravaginal delivery of doxycycline for the treatment of sexually transmitted infections.
authors.affiliation: The University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, Brisbane, Queensland, Australia. Electronic address: meenakshipathak_84@yahoo.com.au.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Pathak
authors.affiliation: School of Pharmacy, The International Medical University, Bukit Jalil, Kuala Lumpur 57000, Malaysia.
authors.forename: Allan G A
authors.initials: AGA
authors.lastname: Coombes
authors.affiliation: The University of Queensland, School of Agriculture and Food Sciences, St. Lucia, Queensland QLD 4072, Australia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Turner
authors.affiliation: Princess Alexandra Hospital, Infection Management Services, Woolloongabba, Queensland QLD 4102, Australia.
authors.forename: Cheryn
authors.initials: C
authors.lastname: Palmer
authors.affiliation: The University of Queensland, Centre of Nutrition and Food Science, St. Lucia, Queensland QLD 4072, Australia.
authors.forename: Dongjie
authors.initials: D
authors.lastname: Wang
authors.affiliation: The University of Queensland, Pharmacy Australia Centre of Excellence, Woolloongabba, Brisbane, Queensland, Australia.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Steadman
mesh_terms: D000282:Administration, Intravaginal; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D004318:Doxycycline / Q000737:chemistry* / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods; D009344:Neisseria gonorrhoeae / Q000187:drug effects; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D011091:Polyesters; D011108:Polymers; C016240:polycaprolactone; D004318:Doxycycline
keywords: Differential scanning calorimetry (DSC); controlled delivery; crystallinity; drug delivery systems; microporous material; polycaprolactone polymer; polymeric drug delivery