title: The effects of topically applied polyNIPAM-based nanogels and their monomers on skin cyclooxygenase expression, ex vivo.
abstract: Stimulus-responsive nanogels have potential as carriers for drugs targeting the skin. It is important to estimate the biocompatibility of such materials with the skin since they are directly in contact upon application and may induce irritation or inflammation. In the current work, blank (drug-free) polyN-isopropylacrylamide (polyNIPAM), poly(NIPAM copolymerized butyl acrylate) [poly(NIPAM-co-BA)], and poly(NIPAM copolymerized with 5% w/v acrylic acid) [poly(NIPAM-co-AAc)(5%)] nanogels were dosed onto freshly excised full-thickness porcine ear skin and the effects on the expression of cyclooxygenase-2 (COX-2) determined ex vivo by Western blotting. Modulated COX-2 expression was indicative that the material had penetrated the skin and keratinocytes of the viable epidermis. The poly(NIPAM-co-BA) nanogel was found to exert a proinflammatory response when applied topically, as reflected by 67% higher COX-2 expression relative to the control treatment (p = 0.0035). The data obtained for the poly(NIPAM-co-AAc)(5%) nanogel, on the other hand, indicated no significant modulation in the expression of COX-2 (p = 0.1578), suggesting the particles are compatible with skin. This was even the case in the presence of co-administered aqueous citric acid solution. Overall the data support the use of the multi-responsive poly(NIPAM-co-AAc)(5%) nanogel for triggered or controlled topical drug delivery applications.
authors.affiliation: Cardiff School of Pharmacy & Pharmaceutical Sciences, Cardiff University , Cardiff , UK.
authors.forename: Nor H
authors.initials: NH
authors.lastname: Abu Samah
authors.forename: Charles M
authors.initials: CM
authors.lastname: Heard
mesh_terms: D000179:Acrylates / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D000287:Administration, Topical; D000818:Animals; D015153:Blotting, Western; D051546:Cyclooxygenase 2 / Q000032:analysis / Q000378:metabolism*; D000080385:Nanogels; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D011094:Polyethyleneimine / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013552:Swine
chemical_list: D000179:Acrylates; D000180:Acrylic Resins; D000080385:Nanogels; C413692:polyethylene glycol polyethyleneimine nanogel; C052970:poly-N-isopropylacrylamide; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D051546:Cyclooxygenase 2