title: Improving the topical ocular pharmacokinetics of an immunosuppressant agent with mucoadhesive nanoemulsions: Formulation development, in-vitro and in-vivo studies.
abstract: Topical ocular conditions such as cornea transplant rejection and keratoconjunctivitis sicca (so called dry eye disease) require therapeutic concentration of immunosuppressant onto the ocular surface for prolonged period. Based on this rational, we optimized cyclosporine A (Cy-A) loaded polymeric mucoadhesive nanoemulsion (Cy-A-mN) with higher Cy-A payload, improved ocular retention, corneal and conjunctival bioavailability. The concentrations of oil, surfactant and co-surfactant needed for the stable nanoemulsion were screened followed by phase behavior study of the formulations components by the construction of pseudo-ternary phase diagrams. The concentration of chitosan was optimized according to the blinking force of eyelids. The size distribution, surface charge, mucoadhesiveness and Cy-A release were studied for Cy-A-mN along with other formulations. The corneal retention of Cy-A-mN was evaluated by gamma scintigraphy, revealing that the clearance was slowest in the case of Cy-A-mN. Biodistribution performed in rabbits showed that Cy-A-mN was able to maintain the therapeutic concentrations (≥50-300ng/g) of Cy-A in the cornea and conjunctiva over the period of 24h. The safety of formulation was confirmed by Draize's test and by measuring the ocular surface temperature.
authors: Nucleic Acids Transfer by Non Viral Methods, Centre de BiophysiqueMoléculaire, CNRS UPR4301, Rue Charles Sadron, 45071 Orléans Cedex 2, France; LE STUDIUM(®) Loire Valley Institute for Advanced Studies, Centre-Val de Loire Region, France; Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, 110062 New Delhi, India. Electronic address: sohailakhtermph@gmail.com.
authors: Sohail
authors: S
authors: Akhter
authors: Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, 110062 New Delhi, India.
authors: Mohammed
authors: M
authors: Anwar
authors: Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, 110062 New Delhi, India.
authors: Mohammad Ahsan
authors: MA
authors: Siddiqui
authors: Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, 110062 New Delhi, India.
authors: Iqbal
authors: I
authors: Ahmad
authors: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli 229010, Uttar Pradesh, India.
authors: Javed
authors: J
authors: Ahmad
authors: Department of Pharmaceutics, College of Pharmacy, Najran University, Saudi Arabia.
authors: Mohammad Zaki
authors: MZ
authors: Ahmad
authors: Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence R&D Organisation, Brig. SK Mazumdar Road, Delhi 110054, India.
authors: Aseem
authors: A
authors: Bhatnagar
authors: Nanomedicine Research Lab, Faculty of Pharmacy, Jamia Hamdard, 110062 New Delhi, India.
authors: Farhan Jalees
authors: FJ
authors: Ahmad
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D001682:Biological Availability; D004655:Emulsions; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology; D011817:Rabbits; D013816:Thermodynamics; D014014:Tissue Adhesives
chemical_list: D004655:Emulsions; D007166:Immunosuppressive Agents; D014014:Tissue Adhesives
keywords: Chitosan; Cyclosporine-A; Draize’s test; Gamma scintigraphy; Immunosuppressant; Mucoadhesive nanoemulsion; Ocular surface temperature; UPLC/Q-TOF-MS/MS