Poly(N-isopropylacrylamide-co-N-vinylpyrrolidone) thermoresponsive microspheres: The low drug loading ensures the pulsatile release mechanism

. Poly( N -isopropylacrylamide- co - N -vinylpyrrolidone) (poly(NIPAAm- co -NVP)) with a co-monomer molar ratio in copolymer of 91.5/8.5 (NIPAAm/NVP) was synthesized as an interesting thermosensitive material possessing a sharp phase transition at 36°C under simulated physiological conditions. The effect of the co-monomer molar ratio as well as of the ionic strength and nature of ions on the lower critical solution temperature (LCST) was investigated. Cross-linked poly(NIPAAm -co- NVP) thermoresponsive microspheres were synthesized by the suspension polymerization technique re-specting the same NIPAAm/NVP molar ratio as for linear polymer. The microspheres were loaded with the model drug diclofenac (DF) by the solvent evaporation method; differential scanning calorimetry (DSC) demonstrates a dispersion of drug crystals within the polymeric matrix. The DF release rate is deeply influenced by the drug loading degree. Only microspheres with low DF loading are able to release the bioactive compound through a pulsatile mechanism.

[1]  P. Ilgin,et al.  A new dual stimuli responsive hydrogel: Modeling approaches for the prediction of drug loading and release profile , 2019, European Polymer Journal.

[2]  J. Chaudhary,et al.  Anionic carboxymethylagarose-based pH-responsive smart superabsorbent hydrogels for controlled release of anticancer drug. , 2019, International journal of biological macromolecules.

[3]  D. Kuckling,et al.  Light‐responsive nanoparticles based on new polycarbonate polymers as innovative drug delivery systems for photosensitizers in PDT , 2019, International journal of pharmaceutics.

[4]  Y. Jeong,et al.  Magnetically Responsive Drug Delivery Using Doxorubicin and Iron Oxide Nanoparticle-Incorporated Lipocomplexes. , 2019, Journal of nanoscience and nanotechnology.

[5]  Fan Huang,et al.  Nitrilotriacetic Acid-Functionalized Glucose-Responsive Complex Micelles for the Efficient Encapsulation and Self-Regulated Release of Insulin. , 2018, Langmuir : the ACS journal of surfaces and colloids.

[6]  M. Pereira-da-Silva,et al.  Curcumin-loaded cationic solid lipid nanoparticles as a potential platform for the treatment of skin disorders. , 2017, Die Pharmazie.

[7]  Xiaoliang Qi,et al.  Synthesis and characterization of a multi-sensitive polysaccharide hydrogel for drug delivery. , 2017, Carbohydrate polymers.

[8]  Y. Gal,et al.  Redox-responsive core cross-linked prodrug micelles prepared by click chemistry for pH-triggered doxorubicin delivery , 2017 .

[9]  R. Boukherroub,et al.  Electrochemically triggered release of drugs , 2016 .

[10]  Xiaohong Hu,et al.  A new route to fabricate biocompatible hydrogels with controlled drug delivery behavior. , 2016, Journal of colloid and interface science.

[11]  P. Zahedi,et al.  Electrospun poly (N-isopropylacrylamide-co-acrylic acid)/cellulose laurate blend nanofibers containing adapalene: Morphology, drug release, and cell culture studies , 2016 .

[12]  Elaine Aparecida Armelín Diggroc,et al.  Semiconducting, biodegradable and bioactive fibers for drug delivery , 2016 .

[13]  P. Ascenzi,et al.  Poly(NIPAAm-co-β-cyclodextrin) microgels with drug hosting and temperature-dependent delivery properties ☆ , 2014 .

[14]  Xuguang Liu,et al.  Magnetic thermosensitive core/shell microspheres: synthesis, characterization and performance in hyperthermia and drug delivery , 2014 .

[15]  P. Ascenzi,et al.  Poly(N-isopropylacrylamide-co-hydroxyethylacrylamide) thermosensitive microspheres: the size of microgels dictates the pulsatile release mechanism. , 2013, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[16]  P. Ascenzi,et al.  The thermosensitivity of pH/thermoresponsive microspheres activated by the electrostatic interaction of pH-sensitive units with a bioactive compound. , 2013, Journal of biomedical materials research. Part A.

[17]  Wei Gao,et al.  Synthesis of hydrophilic microspheres with LCST close to body temperature for controlled dual-sensitive drug release , 2011 .

[18]  James P. Keener,et al.  Kinetics of Swelling Gels , 2011, SIAM J. Appl. Math..

[19]  P. Ascenzi,et al.  Entrapment and release of drugs by a strict "on-off" mechanism in pullulan microspheres with pendant thermosensitive groups. , 2010, Biomaterials.

[20]  Yanbin Huang,et al.  A thermal analysis method to predict the complete phase diagram of drug-polymer solid dispersions. , 2010, International journal of pharmaceutics.

[21]  Jun Hu,et al.  Chain collapse and revival thermodynamics of poly(N-isopropylacrylamide) hydrogel. , 2010, The journal of physical chemistry. B.

[22]  Prasanta Chowdhury,et al.  Kinetic modeling on drug release from controlled drug delivery systems. , 2010, Acta poloniae pharmaceutica.

[23]  P. Ascenzi,et al.  Fast-responsive porous thermoresponsive microspheres for controlled delivery of macromolecules. , 2009, International journal of pharmaceutics.

[24]  P. Ascenzi,et al.  pH- and temperature-sensitive polymeric microspheres for drug delivery: the dissolution of copolymers modulates drug release , 2009, Journal of materials science. Materials in medicine.

[25]  P. Ascenzi,et al.  Poly(N-isopropylacrylamide-co-acrylamide) cross-linked thermoresponsive microspheres obtained from preformed polymers: Influence of the physico-chemical characteristics of drugs on their release profiles. , 2009, Acta biomaterialia.

[26]  David S. Jones,et al.  Characterization of the physicochemical, antimicrobial, and drug release properties of thermoresponsive hydrogel copolymers designed for medical device applications. , 2008, Journal of biomedical materials research. Part B, Applied biomaterials.

[27]  Chi-Hwa Wang,et al.  Mathematical modeling and simulation of drug release from microspheres: Implications to drug delivery systems. , 2006, Advanced drug delivery reviews.

[28]  O. Corrigan,et al.  Preparation and release of model drugs from thermally sensitive poly(N-isopropylacrylamide) based macrospheres , 2006, Journal of microencapsulation.

[29]  P. Ascenzi,et al.  Preparation and characterisation of thermoresponsive poly[(N-isopropylacrylamide-co-acrylamide-co-(hydroxyethyl acrylate)] microspheres as a matrix for the pulsed release of drugs. , 2005, Macromolecular bioscience.

[30]  Justin D. Debord,et al.  Synthesis and characterization of pH-responsive copolymer microgels with tunable volume phase transition temperatures , 2003 .

[31]  B. Işık,et al.  Synthesis and characterization of thermoresponsive isopropylacrylamide-acrylamide hydrogels , 2002 .

[32]  F. Candau,et al.  Synthesis in microemulsion and characterization of stimuli-responsive polyelectrolytes and polyampholytes based on N-isopropylacrylamide , 2001 .

[33]  A. Moes,et al.  Effect of some physiological and non-physiological compounds on the phase transition temperature of thermoresponsive polymers intended for oral controlled-drug delivery. , 2001, International journal of pharmaceutics.

[34]  Nicholas A. Peppas,et al.  A model of dissolution-controlled, diffusional drug release from non-swellable polymeric microspheres , 1988 .

[35]  Toyoichi Tanaka,et al.  Kinetics of discontinuous volume-phase transition of gels , 1988 .

[36]  A. Hoffman,et al.  Lower critical solution temperatures of aqueous copolymers of N-isopropylacrylamide and other N-substituted acrylamides , 1987 .

[37]  M. Ataman.  Properties of aqueous salt solutions of poly(ethylene oxide). Cloud points, θ temperatures , 1987 .

[38]  F. Haaf,et al.  Polymers of N-Vinylpyrrolidone: Synthesis, Characterization and Uses , 1985 .

[39]  N. Peppas,et al.  Mechanisms of solute release from porous hydrophilic polymers , 1983 .

[40]  E. A. Boucher,et al.  Properties of aqueous salt solutions of poly(ethylene oxide) , 1982 .