Synthesis and evaluation of luliconazole loaded biodegradable nanogels prepared by pH-responsive Poly (acrylic acid) grafted Sodium Carboxymethyl Cellulose using amine based cross linker for topical targeting: In vitro and Ex vivo assessment

ABSTRACT

Fungal infection in immuno compromised patients causes skin syndromes and problems. At Present, innovative alternatives are required to cure skin disorders and infections. Luliconazole is a novel, broad spectrum, imidazole antifungal agent. The purpose of this study was to develop biodegradable, pH responsive, chemically cross-linked and Poly (acrylic acid) grafted sodium carboxymethyl cellulose nanogels. Nanogels had been synthesized to evaluate its applicability as an effective carrier of luliconazole for topical (skin) targeting. Chemically cross-linked sodium carboxymethyl cellulose-grafted-Poly acrylic acid (NaCMC-g-PAA) was synthesized from acrylic acid and sodium carboxymethyl cellulose using N, N’-methylene bisacrylamide (cross-linker) and potassium persulfate (initiator) using free radical polymerization. Variation of reaction parameters such as pH, cross linker, initiator and temperature has been used to optimize the best one. The developed nanogels reveal significant pH sensitive drug releasing behavior. NaCMC-g-PAA nanogels has been characterized using various physicochemical characterization techniques. Nanogels characteristics were evaluated through the In vitro drug release, Ex vivo permeation study, Nuclear magnetic resonance spectroscopy, Fourier Transform Infrared Spectroscopy, Field Emission Scanning Electron Microscope, Stability Study and antifungal activity. All batches were characterized for particle size analysis and ranged from 78.82 nm to 190 nm. The viscosity of developed nanogels was found to be 5941 cps. It was observed that the developed drug-loaded NaCMC-g-PAA nanogels were more effective in killing the fungus. Consequently, Nanogels incorporated with luliconazole could be a new approach with improved antifungal activity and increased topical delivery for a drug with poor aqueous solubility rather than coarse drug-containing cream.

GRAPHICAL ABSTRACT

KEYWORDS:

• Luliconazole
• poly (acrylic acid)
• pH
• nanogels
• topical delivery

Acknowledgments

Authors would like to acknowledge the Technical Education Quality Improvement Program (TEQIP-III), World Bank and MHRD, New Delhi for providing financial assistance to carry out this research work. The authors also acknowledge Sun Pharma Ltd. India for providing gift sample of Luliconazole.

Conflict of the interest

These authors declare that they have no conflict of interest.

Additional information

Funding

This work was supported by the Technical Education Quality Impprovement Program (TEQIP-III) [DTE/SPFU/2017-18/95], World Bank and MHRD, New Delhi.

Notes on contributors

Rahul L. Rajput

Rahul L. Rajput is post graduate in Pharmaceutical Technology and having 4 years of research experience in taste masking, drug delivery, and microencapsulation.

Jitendra S. Narkhede

Jitendra S. Narkhede is an Assistant Professor at University Institute of Chemical Technology, KBC North Maharashtra University, Jalgaon and having 10 years of research experience in polymer synthesis, flame retardants, and polymer composites.

Arun Mujumdar

Arun Mujumdar is an Adjunct Research Professor at Department of Chemical & Biochemical Engineering, Western University, London, Ontario, Canada and having 35 years of experience in advanced thermal drying and dewatering processes, modeling transport phenomena, energy systems, thermal fluid engineering and science as well as food processing.

Jitendra B. Naik

Jitendra B. Naik is Director at University Institute of Chemical Technology, KBC North Maharashtra University, Jalgaon and having 24 years of research experience in the field of nanotechnology, biomedical polymers, drug delivery, taste masking and chemical kinetics.