Stability, safety, and transcorneal mechanistic studies of ophthalmic lyophilized cyclosporine-loaded polymeric micelles
| Autor: | Ying Xu, Xiaolian Li, Birendra Chaurasiya, Runing Sun, Yan Shen, Jiasheng Tu, Yinglan Yu, Thomas J. Webster |
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| Rok vydání: | 2018 |
| Předmět: |
Polymers
Proton Magnetic Resonance Spectroscopy mPEG-PLA micelles physicochemical characteristics Pharmaceutical Science 02 engineering and technology 030226 pharmacology & pharmacy Ring-opening polymerization Micelle Polyethylene Glycols Polymerization Cornea chemistry.chemical_compound 0302 clinical medicine International Journal of Nanomedicine Drug Discovery Cytotoxicity Micelles Original Research chemistry.chemical_classification Drug Carriers Cell Death Temperature General Medicine Polymer Hydrogen-Ion Concentration CsA 021001 nanoscience & nanotechnology Paracellular transport Cyclosporine Irritants Rabbits 0210 nano-technology Immunosuppressive Agents Polyesters lyophilization Biophysics Bioengineering Fluorescence Cell Line Biomaterials 03 medical and health sciences Animals Humans Particle Size Lactide Organic Chemistry Drug Liberation Freeze Drying Solubility chemistry Ophthalmic Solutions Nanocarriers transcorneal mechanism Ethylene glycol |
| Zdroj: | International Journal of Nanomedicine |
| ISSN: | 1178-2013 |
| DOI: | 10.2147/ijn.s173691 |
| Popis: | Yan Shen,1,* Yinglan Yu,1,* Birendra Chaurasiya,1 Xiaolian Li,1 Ying Xu,2 Thomas J Webster,3 Jiasheng Tu,1 Runing Sun4 1Department of Pharmaceutics, Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, School of Pharmacy, China Pharmaceutical University, Nanjing, China; 2College of Pharmacy, Jiangsu University, Zhenjiang, China; 3Department of Chemical Engineering, Northeastern University, Boston, MA, USA; 4School of Engineering, China Pharmaceutical University, Nanjing, China *These authors contributed equally to this work Introduction: Cyclosporine-A (CsA) is generally used as an immunosuppressant and is also prescribed for some ophthalmic applications such as vernal keratoconjunctivitis and dry eye. However, it is limited clinically due to its low aqueous solubility and ocular bioavailability.Methods: In this work, lyophilized methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA) polymer micelles were prepared for ophthalmic formulations as a promising nano-carrier for hydrophobic drugs like CsA. A mPEG-PLA diblock polymer was synthesized by ring opening polymerization and CsA was loaded into mPEG-PLA micelles by a simple film dispersion method. A uniform design of experiments was utilized to optimize the final formulation. The obtained formulation was characterized for diameter (57.0±3.2 nm), entrapment efficiency % (98.51±1.4), and in vitro release. Moreover, incorporating the stabilizer mPEG2000 could increase the in vitro stability of the lyophilized CsA-loaded mPEG-PLA micelles.Results: Results showed a sustained release of CsA from the micelles. Drug concentration and time-dependent cytotoxicity of human corneal epithelial-2 cells was observed. Additionally, the transcorneal mechanism of mPEG-PLA micelles was studied and the results showed that the mPEG-PLA micelles mainly absorbed by a paracellular pathway via corneal epithelial cells.Conclusion: Taken together, the results proved that this mPEG-PLA diblock polymer can be potentially used as a nanoscopic carrier to deliver hydrophobic drugs in a controlled manner to the ocular region and, thus, deserves further attention. Keywords: CsA, mPEG-PLA micelles, lyophilization, physicochemical characteristics, transcorneal mechanism |
| Databáze: | OpenAIRE |
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