title: Engineering of polymer-surfactant nanoparticles of doxycycline hydrochloride for ocular drug delivery.
abstract: BACKGROUND
  Physiologic barriers of the eye, short precorneal drug residence time and poor corneal penetration are the few reasons for reduced ocular bioavailability.
  
  
  OBJECTIVE
  This study was aimed to develop novel polymer-surfactant nanoparticles of hydrophilic drug doxycycline hydrochloride (DXY) to improve precorneal residence time and drug penetration.
  
  
  METHODS
  Nanoparticles were formulated using emulsion cross-linking method and the formulation was optimized using factorial design. The prepared formulation was characterized for particle size, ζ potential, encapsulation efficiency, in vitro drug release and ex vivo drug diffusion studies. The antibacterial activity studies were also carried out against Escherichia coli and Staphylococcus aureus using the cup-plate method. In vivo eye irritation study was carried out by a modified Draize test in rabbits.
  
  
  CONCLUSIONS
  The particle size was found to be in the range of 331-850 nm. About 45-80% of the drug was found to be encapsulated in the nanoparticles. In vitro release demonstrated sustained release profile. Lower flux values in case of nanoparticles as compared to DXY pure drug solution in ex vivo diffusion studies confirmed the sustained release. The nanoparticles were found to be significantly effective (p < 0.001) than DXY aqueous solution due to sustained release of doxycycline from nanoparticles in both the E. coli and S. aureus strains. The formulation was found to be stable over entire stability period.
  
  
  CONCLUSIONS
  The developed formulation is safe and suitable for sustained ocular drug delivery.
authors.affiliation: a Department of Pharmaceutics, Poona College of Pharmacy , Bharati Vidyapeeth University , Pune , Maharashtra , India.
authors.forename: Varsha
authors.initials: V
authors.lastname: Pokharkar
authors.affiliation: a Department of Pharmaceutics, Poona College of Pharmacy , Bharati Vidyapeeth University , Pune , Maharashtra , India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Patil
authors.affiliation: a Department of Pharmaceutics, Poona College of Pharmacy , Bharati Vidyapeeth University , Pune , Maharashtra , India.
authors.forename: Leenata
authors.initials: L
authors.lastname: Mandpe
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003315:Cornea / Q000378:metabolism; D003692:Delayed-Action Preparations; D004318:Doxycycline / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions; D004926:Escherichia coli / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D013211:Staphylococcus aureus / Q000187:drug effects; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D011108:Polymers; D013501:Surface-Active Agents; D004318:Doxycycline
keywords: Emulsion cross-linking method; factorial design; gellan gum; polymer–surfactant nanoparticles; sustained release