Studying the influence of formulation and process variables on Vancomycin-loaded polymeric nanoparticles as potential carrier for enhanced ophthalmic delivery

• Published in: European journal of pharmaceutical sciences Vol. 100; pp. 142 - 154
• Main Authors: Yousry, Carol, Elkheshen, Seham A., El-laithy, Hanan M., Essam, Tamer, Fahmy, Rania H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30-03-2017
• Subjects: Acrylic Resins - chemistry; Administration, Ophthalmic; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - toxicity; Draize test; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Drug Carriers - toxicity; Drug Compounding; Drug Liberation; Gels; Hydrogen-Ion Concentration; Microbiological susceptibility testing; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoparticles - toxicity; Ocular infection; Poly (d,l-lactide- coglycolide) (PLGA); Polycaprolactone (PCL); Rabbits; Staphylococcus aureus - drug effects; Vancomycin; Vancomycin - administration & dosage; Vancomycin - chemistry; Vancomycin - toxicity; EE; VCM; PS; PNPs; STF; Ocular infection; Poly (d,l-lactide- coglycolide) (PLGA); Microbiological susceptibility testing; Vancomycin; ACN; PLGA; DW; PDI; ANOVA; ZP; FTIR; MRSA; PCL; Draize test; SEM; Polycaprolactone (PCL); TEM; PM
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2017.01.013

Ocular topically applied Vancomycin (VCM) suffers poor bioavailability due to its high molecular weight and hydrophilicity. In the present investigation, VCM-loaded polymeric nanoparticles (PNPs) were developed aiming to enhance its ocular bioavailability through prolonging its release pattern and ophthalmic residence. PNPs were prepared utilizing double emulsion (W/O/O), solvent evaporation technique. 23×41 full factorial design was applied to evaluate individual and combined influences of polymer type, Eudragit® RS100, sonication time, and Span®80 concentration on PNPs particle size, encapsulation efficiency, and zeta potential. Further, the optimized formulae were incorporated in 1% Carbopol®-based gel. In-vivo evaluation of the optimized formulae was performed via Draize test followed by microbiological susceptibility testing on albino rabbits. Results revealed successful formulation of VCM-loaded PNPs was achieved with particle sizes reaching 155nm and up to 88% encapsulation. Draize test confirmed the optimized formulae as non-irritating and safe for ophthalmic administration. Microbiological susceptibility testing confirmed prolonged residence, higher Cmax. with more than two folds increment in the AUC(0.25–24) of VCM-PNPs over control groups. Thus, VCM-loaded PNPs represent promising carriers with superior achievements for enhanced Vancomycin ophthalmic delivery over the traditional use of commercially available VCM parenteral powder after constitution into a solution by the ophthalmologists.
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