title: Design of nanosuspensions and freeze-dried PLGA nanoparticles as a novel approach for ophthalmic delivery of pranoprofen.
abstract: Pranoprofen (PF)-loaded poly (lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were optimized and characterized as a means of exploring novel formulations to improve the biopharmaceutical profile of this drug. These systems were prepared using the solvent displacement technique, with polyvinyl alcohol (PVA) as a stabilizer. A factorial design was applied to study the influence of several factors (the pH of the aqueous phase and the stabilizer, polymer and drug concentrations) on the physicochemical properties of the NPs. After optimization, the study was performed at two different aqueous phase pH values (4.50 and 5.50), two concentrations of PF (1.00 and 1.50 mg/mL), three of PVA (5, 10, and 25 mg/mL), and two of PLGA (9.00 and 9.50 mg/mL). These conditions produced NPs of a size appropriate particle size for ocular administration (around 350 nm) and high entrapment efficiency (80%). To improve their stability, the optimized NPs were lyophilized. X-ray, FTIR, and differential scanning calorimetry analysis confirmed the drug was dispersed inside the particles. The release profiles of PF from the primary nanosuspensions and rehydrated freeze-dried NPs were similar and exhibited a sustained drug delivery pattern. The ocular tolerance was assessed by an HET-CAM test. No signs of ocular irritancy were detected (score 0).
authors.affiliation: Department of Physical Chemistry, Faculty of Pharmacy, University of Barcelona, Barcelona, 08028, Spain; Department of Biopharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Barcelona, Barcelona, 08028, Spain.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Abrego
authors.forename: Helen L
authors.initials: HL
authors.lastname: Alvarado
authors.forename: Maria A
authors.initials: MA
authors.lastname: Egea
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gonzalez-Mira
authors.forename: Ana C
authors.initials: AC
authors.lastname: Calpena
authors.forename: Maria L
authors.initials: ML
authors.lastname: Garcia
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001578:Benzopyrans / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D005612:Freeze Drying; D019344:Lactic Acid / Q000737:chemistry*; D053758:Nanoparticles; D049329:Nanostructures; D009883:Ophthalmic Solutions; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011422:Propionates / Q000008:administration & dosage*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D009883:Ophthalmic Solutions; D011422:Propionates; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; C043940:pyranoprofen; D019344:Lactic Acid
keywords: biodegradable polymers; factorial design; freeze-drying/lyophilization; nanoparticles; poly (lactic/glycolic) acid (PLGA); polymeric drug delivery system; pranoprofen; stability