title: Thermoresponsive polymeric gel as an on-demand transdermal drug delivery system for pain management.
abstract: The main aim of this work is to design a heat triggered transdermal drug delivery system (TDDS) using a thermoresponsive polymer, poly (N-vinyl caprolactam) [PNVCL] based gel, where in patients can themselves administer a pulse of drug on mere application of heat pad over the TDDS, whenever pain is experienced. The phase transition temperature of PNVCL was tuned to 35 °C by grafting it onto a pH sensitive biopolymer, Chitosan, to synthesize Chitosan-g-PNVCL (CP) co-polymer which render the gel both thermo- and pH-responsive property. The application of triggered delivery was explored by loading acetamidophenol (a model hydrophilic drug) and etoricoxib (a model hydrophobic drug). In vitro drug release experiments were performed at three different temperatures (25, 32 and 39 °C) at two different pH (5.5 and 7) to study its drug release with response to temperature and pH. Drug release profiles obtained were found to have enhanced release for both the drugs respectively at 39 °C (above LCST) and pH5.5 when compared to other release conditions. In vitro skin permeation of both the drugs performed in rat abdominal skin using Franz diffusion cell showed enhanced drug release when the skin was subjected to higher temperature (39 °C). Moreover, it was also found that skin permeation for hydrophobic drug was better than that of hydrophilic drug. The in vivo biocompatibility studies of the CP gel in rat skin proved that the gel is biocompatible. The results obtained demonstrated the potential use of the thermoresponsive CP gel as an on-demand localized drug delivery system.
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.
authors.forename: S
authors.initials: S
authors.lastname: Indulekha
authors.affiliation: Centre for Research in Nanotechnology and Science, Indian Institute of Technology Bombay, Mumbai 400076, India.
authors.forename: P
authors.initials: P
authors.lastname: Arunkumar
authors.affiliation: Department of Metallurgical Engineering and Materials Science, Indian Institute of Technology Bombay, Mumbai 400076, India.
authors.forename: D
authors.initials: D
authors.lastname: Bahadur
authors.affiliation: Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India. Electronic address: rsrivasta@iitb.ac.in.
authors.forename: R
authors.initials: R
authors.lastname: Srivastava
mesh_terms: D000082:Acetaminophen / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D000279:Administration, Cutaneous; D018712:Analgesics, Non-Narcotic / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D004058:Diffusion; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D065546:Drug Liberation; D000077613:Etoricoxib; D005782:Gels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D051379:Mice; D059408:Pain Management; D044367:Phase Transition; D011108:Polymers / Q000737:chemistry*; D011725:Pyridines / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013450:Sulfones / Q000032:analysis / Q000737:chemistry* / Q000494:pharmacology; D044366:Transition Temperature
chemical_list: D018712:Analgesics, Non-Narcotic; D001672:Biocompatible Materials; D004337:Drug Carriers; D005782:Gels; D011108:Polymers; D011725:Pyridines; D013450:Sulfones; D000082:Acetaminophen; D048271:Chitosan; D000077613:Etoricoxib
keywords: LCST; On-demand; Thermoresponsive; Transdermal; pH responsive; poly (N-vinyl caprolactam)