title: Synthesis and characterization of thermoresponsive copolymers for drug delivery.
abstract: We report the synthesis and characterization of two nontoxic, thermogelling drug delivery systems which are liquid at room temperatures but become a gel at physiological temperature (37°C) potentially leading to release of a drug molecule. We selected temperature as the stimulus for drug release as it is physiologically invariant. A free radical polymerization of N-isopropylacrylamide (NIPAM) and N-vinylpyrrolidone (VP) was carried out under nitrogen atmosphere in double-distilled water at two different temperatures (30°C and 70°C), and the copolymers obtained were characterized by various analytical techniques. The molar ratios of the two monomers were altered with increasing NIPAM content and their cloud point temperature or least critical solution temperature (LCST) was determined. The copolymer at 9:1 ratio of NIPAM to VP resulted in the formation of nanoparticle-based gel (NG1) at 30°C; however, at 70°C, a microgel (MG1) was formed. The LCST of the nanogel and microgel was 33.5-34°C and 36.5-37°C, respectively. Thus, both the copolymers are water soluble at room temperature, but distinct phases appear at physiological temperatures. We hypothesized that these copolymers on entrapment with a drug could be used for topical application to the skin or eye for controlled drug delivery applications. Toxicological studies revealed that the copolymers are nontoxic in HeLa cells. Finally, our experiments show that a model drug [bovine serum albumin (BSA)] is released at 37°C with zero-order kinetics and confirmed using multiple well-known mathematical models.
authors.affiliation: Department of Chemistry, University of Delhi, Delhi 110007, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Aerry
authors.forename: Arnab
authors.initials: A
authors.lastname: De
authors.forename: Ajeet
authors.initials: A
authors.lastname: Kumar
authors.forename: Amit
authors.initials: A
authors.lastname: Saxena
authors.forename: D K
authors.initials: DK
authors.lastname: Majumdar
authors.forename: Subho
authors.initials: S
authors.lastname: Mozumdar
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry; D012542:Scattering, Radiation; D012710:Serum Albumin, Bovine / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D008823:Micelles; D011108:Polymers; D011760:Pyrrolidinones; C052970:poly-N-isopropylacrylamide; D012710:Serum Albumin, Bovine; C042670:N-vinyl-2-pyrrolidinone