title: Enhanced in vitro transdermal delivery of caffeine using a temperature- and pH-sensitive nanogel, poly(NIPAM-co-AAc).
abstract: Temperature- and pH-responsive poly(N-isopropylacrylamide) (polyNIPAM) copolymerised with 5% (w/v) of acrylic acid (AAc), termed as poly(NIPAM-co-AAc) nanogel was investigated as a novel multi-responsive topical drug delivery carrier, using caffeine as a model permeant. The role of a pH modulator (citric acid) on the nanogel system was also studied. The loading was carried out in deionised water at two different temperatures, which were 2-4°C and 25°C (room temperature, RT) over 3 days. The loading of caffeine into the poly(NIPAM-co-AAc) nanogel was found to be significantly higher at 2-4°C than at RT (p=0.0072). As for the control nanogel (polyNIPAM), a similar pattern of loading level can be observed (p=0.0005). This enhanced loading at low temperatures could be attributed to the hydrophilic behaviour of the polyNIPAM network in response to temperatures lower than its lower critical solution temperature (LCST). In vitro diffusion studies across epidermis porcine skin were carried out at 32°C for the saturated solution of caffeine as well as caffeine-loaded poly(NIPAM-co-AAc) and polyNIPAM nanogels. The in vitro permeation data of caffeine-loaded poly(NIPAM-co-AAc) at 2-4°C were shown to enhance the delivery of the loaded caffeine across the epidermis in comparison to the saturated solution of caffeine, by 3.5 orders of magnitude. Additionally, the study demonstrated that the effect of pH modulator on the release of loaded permeant was insignificant.
authors.affiliation: Welsh School of Pharmacy, Cardiff University, Cardiff CF10 3NB, United Kingdom.
authors.forename: Nor H
authors.initials: NH
authors.lastname: Abu Samah
authors.forename: Charles M
authors.initials: CM
authors.lastname: Heard
mesh_terms: D000178:Acrylamides / Q000008:administration & dosage* / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage* / Q000737:chemistry; D005782:Gels; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D013552:Swine; D013696:Temperature
chemical_list: D000178:Acrylamides; D005782:Gels; C090629:N-isopropylacrylamide-acrylic acid copolymer; D011108:Polymers; D002110:Caffeine
keywords: Acrylic acid; NIPAM; Nanogel; Stimulus responsive; Temperature; pH