title: Formulation and release behavior of doxycycline-alginate hydrogel microparticles embedded into pluronic F127 thermogels as a potential new vehicle for doxycycline intradermal sustained delivery.
abstract: The aim of this work was the formulation and characterization of alginate (ALG)-doxycycline (DOX) hydrogel microparticles (MPs) embedded into Pluronic F127 thermogel for DOX intradermal sustained delivery. ALG-DOX MPs were formed by adding a solution of the drug into a 1.5% polymer solution while stirring. The MPs were cross-linked by dispersion into a 1.2% CaCl2 solution. Free MPs were characterized in terms of size, drug content, and release behavior by HPLC and UV-vis. DOX and hydrogel MPs were embedded into PF127, PF127-HPMC, and PF127-Methocel thermogels. The thermogels were characterized in terms of gelling time, morphology, and release behavior. A target release period of 4-7 days was considered optimal. The hydrogel MPs were about 20 microm in size with 90% of the population <59 microm. Drug content was about 35% (w/w). DOX released rapidly from the MPs, 90% within 2 days. An expected faster release was observed for free DOX from the thermogels with 80-90% of drug released after 3.5-4 h even in the presence of 1% HPMC or Methocel. The release was sustained after embedding the MPs into PF127 and PF127-HPMC thermogels. In particular, the PF127-HPMC thermogel showed an almost linear release, reaching 80% after 3 days and 90% up to 6 days. Although a further characterization and formulation assessment is required to optimize MP characteristics, ALG/DOX-loaded hydrogel MPs, when embedded into a PF127-HPMC thermogel, show a potential for achieving a 7-day sustained release formulation for DOX intradermal delivery.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, University of Perugia, Perugia, Italy. eureka@unipg.it
authors.forename: Stefano
authors.initials: S
authors.lastname: Giovagnoli
authors.forename: Tsuimin
authors.initials: T
authors.lastname: Tsai
authors.forename: Patrick P
authors.initials: PP
authors.lastname: DeLuca
mesh_terms: D000464:Alginates; D002626:Chemistry, Pharmaceutical; D004304:Dosage Forms; D004318:Doxycycline; D005782:Gels; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007271:Injections, Intradermal; D008747:Methylcellulose / Q000737:chemistry; D014677:Pharmaceutical Vehicles; D020442:Poloxamer / Q000737:chemistry*
chemical_list: D000464:Alginates; D004304:Dosage Forms; D005782:Gels; D006603:Hexuronic Acids; D014677:Pharmaceutical Vehicles; D020442:Poloxamer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D020723:Glucuronic Acid; D008747:Methylcellulose; D004318:Doxycycline