Formulation Development, Optimization, and In Vitro-In Vivo Characterization of Natamycin-Loaded PEGylated Nano-Lipid Carriers for Ocular Applications

Akash Patil; Prit Lakhani; Pranjal Taskar; Kai-Wei Wu; Corinne Sweeney; Bharathi Avula; Yan-Hong Wang; Ikhlas A Khan; Soumyajit Majumdar

doi:10.1016/j.xphs.2018.04.014

Formulation Development, Optimization, and In Vitro-In Vivo Characterization of Natamycin-Loaded PEGylated Nano-Lipid Carriers for Ocular Applications

J Pharm Sci. 2018 Aug;107(8):2160-2171. doi: 10.1016/j.xphs.2018.04.014. Epub 2018 Apr 24.

Authors

Akash Patil¹, Prit Lakhani¹, Pranjal Taskar¹, Kai-Wei Wu¹, Corinne Sweeney¹, Bharathi Avula², Yan-Hong Wang², Ikhlas A Khan³, Soumyajit Majumdar⁴

Affiliations

¹ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, Oxford, Mississippi 38677.
² National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford, Mississippi 38677.
³ National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, University of Mississippi, Oxford, Mississippi 38677; Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, University of Mississippi, Oxford, Mississippi 38677.
⁴ Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, Oxford, Mississippi 38677. Electronic address: majumso@olemiss.edu.

PMID: 29698725
DOI: 10.1016/j.xphs.2018.04.014

Abstract

The present study aimed at formulating and optimizing natamycin (NT)-loaded polyethylene glycosylated nano-lipid carriers (NT-PEG-NLCs) using Box-Behnken design and investigating their potential in ocular applications. Response surface methodology computations and plots for optimization were performed using Design-Expert^® software to obtain optimum values for response variables based on the criteria of desirability. Optimized NT-PEG-NLCs had predicted values for the dependent variables which are not significantly different from the experimental values. NT-PEG-NLCs were characterized for their physicochemical parameters; NT's rate of permeation and flux across rabbit cornea was evaluated, in vitro, and ocular tissue distribution was assessed in rabbits, in vivo. NT-PEG-NLCs were found to have optimum particle size (<300 nm), narrow polydispersity index, and high NT entrapment and NT content. In vitro transcorneal permeability and flux of NT from NT-PEG-NLCs was significantly higher than that of Natacyn^®. NT-PEG-NLC (0.3%) showed improved delivery of NT across the intact cornea and provided concentrations statistically similar to the marketed suspension (5%) in inner ocular tissues, in vivo, indicating that it could be a potential alternative to the conventional suspension during the course of fungal keratitis therapy.

Keywords: antiinfective(s); bioavailability; in vitro/in vivo (IVIVC) correlation(s); liposome(s); ophthalmic drug delivery; pegylation.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Administration, Ophthalmic
Animals
Anti-Infective Agents, Local / administration & dosage*
Anti-Infective Agents, Local / pharmacokinetics
Cornea / metabolism*
Drug Carriers / chemistry*
Drug Compounding
Drug Liberation
Lipids / chemistry*
Male
Nanostructures / chemistry
Natamycin / administration & dosage*
Natamycin / pharmacokinetics
Particle Size
Permeability
Polyethylene Glycols / chemistry*
Rabbits

Substances

Anti-Infective Agents, Local
Drug Carriers
Lipids
Polyethylene Glycols
Natamycin

Grants and funding

P20 GM104932/GM/NIGMS NIH HHS/United States