Swelling and drug releasing properties of poly(-isopropylacrylamide) thermo-sensitive copolymer gels

Abstract

A series of N-isopropylacrylamide (NIPAAm) copolymer gels with different hydrophilicities were prepared from NIPAAm, hydrophilic acrylamide (AAm) and hydrophobic butyl methacrylate (BMA). The swelling and thermo-responsive properties of PNIPAAm P(NIPAm-co-BMA) and P(NIPAm-co-AAm) copolymer hydrogels were investigated. The drug loading and releasing behaviors for two kinds of model drug with different hydrophilicities were studied. The result shows that the copolymer gels present negative thermo-sensitivities. The lower critical solution temperature (LCST), equilibrium swelling degree and the initial swelling rate increase as the hydrophilicity of gels increases when the temperature is below the LCST. With increasing gel hydrophilicity the loading ratio for sodium salicylate increases, while for salicylic acid, the reverse is observed. The initial drug releasing rate of sodium salicylate and salicylic acid also increase with increasing gel hydrophilicity. The initial drug releasing rate of sodium salicylate is significantly higher than that of salicylic acid. For salicylic acid which is less hydrophilic, the equilibrium releasing ratio at high temperature is lower than that at low temperature while for sodium salicylate which is more hydrophilic, the equilibrium releasing ratio at high temperature is almost the same as that at low temperature. Equilibrium releasing ratios of the three gels are significantly different from each other for salicylic acid when the temperature is below LCST while the equilibrium releasing ratios of the three gels are all 100% for sodium salicylate.

References

1. Dinarvand R Emanuele A D The use of thermal responsivehydrogels for on-off release of moleculesJounal of Controlled Release 1995 36221227. doi:10.1016/0168‐3659(95)00035‐7
2. Dai H J Chen Q Qin H L Guan Y Shen D Y Hua Y Q Tang Y L Xu J A temperature-responsive copolymer hydrogel in controlleddrug deliveryMacromolecules 2006 39(19)65846589. doi:10.1021/ma060486p
3. Bhattarai N Ramay H R Gunn J Matsen F A Zhang M PEG-grafted chitosan as an injectable thermosensitivehydrogel for sustained protein releaseJournalof Controlled Release 2005 103(3)609624. doi:10.1016/j.jconrel.2004.12.019
4. Feng X Chen L Dong J Li B L Fast responsivetemperature-sensitive hydrogel and its application on bioseparationActa Scientiarun Naturaltium Universitatis Nankaiensis 2005 38(6)3440(in Chinese)
5. Zhang Y L Xu L Yi M Zhai M L Wang J R Ha H F Radiationsynthesis of poly[(dimethylaminoethyl methacrylate)-co-(diallyl dimethyl ammonium chloride)]hydrogels and its application as a carrier for notoginsenoside deliveryEuropean Polymer Journal 2006 42(11)29592967. doi:10.1016/j.eurpolymj.2006.08.008
6. Dong J Chen L Ding Y M Han W J Swelling andmechanical properties of a temperature-sensitive dextran hydrogeland its bioseparation applicationsMacromolecularChemistry and Physics 2005 206(19)19731980. doi:10.1002/macp.200500125
7. Zan J Zhu D Q Tan F P Jiang G Q Lin Y Ding F X Preparationof thermosensitive chitosan formulations containing 5-fluorouracil/poly-3-hydroxybutyratemicroparticles used as injectable drug delivery systemChinese Journal of Chemical Engineering 2006 14(2)235241. doi:10.1016/S1004‐9541(06)60064‐5
8. Lai J H Pan C Y Rao Y P Effect of synthetic temperature on structure and propertiesof poly(N-isopropylacrylamide)gelsJournal of Central South Universityof Technology: Natural Science 2005 36(6)10061010(in Chinese)
9. Zhang J T Huang S W Liu J Zhuo R X Temperaturesensitive poly[N-isopropylacrylamide-co-(acryloyl-β-cyclodextrin)] for improved drug releaseMacromolecular Bioscience 2005 5(3)192196. doi:10.1002/mabi.200400167
10. Caykara T Kiper S Demirel G Thermo-sensitive poly(N-isopropylacrylamide-co-acrylamide)hydrogels: Synthesis, swelling and interaction with ionic surfactantsEuropean Polymer Journal 2006 42(2)348355. doi:10.1016/j.eurpolymj.2005.07.006
11. Iwai K Hanasaki K Yamamoto M Fluorescence label studies of thermo-responsive poly(N-isopropylacrylamide) hydrogelsJournal of Luminescence 2000 87–89(3–4)12891291. doi:10.1016/S0022‐2313(99)00586‐4
12. Zhang J H Yang Y J Stimuli-response of hydrophilic-hydrophobicsemi-IPN gel on acetone-water mixtureJournalof Northeast Normal University: Natural Science Edition 2001 33(2)4751(in Chinese)
13. Zhang J H Stimuliresponse of hydrophilic hydrophobic semi IPN hydrogels on temperatureActa Physico-Chimica Sinica 2003 19(1)9093(in Chinese)
14. Zhang J H Yang Y J Stimuli-response of hydrophilic-hydrophobicsemi-ipn hydrogels under dc electric fieldActa Polymerica Sinica 2002 12529(in Chinese)
15. Li L B Tan Y B Two Sorts of Problems on drugcontrolled release from swellable polymerJournal of Biomedical Engineering 2003 20(1)1721(in Chinese)
16. Kim I S Jeong Y I Cho C S et al.Thermo-responsive self-assembled polymeric micellesfor drug delivery in vitroInternationalJournal of Pharmaceutics 2000 205165172. doi:10.1016/S0378‐5173(00)00501‐9
17. Zhang X Z Zhuo R X Synthesis of temperature-sensitivepoly(N-isopropylacrylamide) hydrogelwith improved surface propertyJournal ofColloid and Interface Science 2000 233311313. doi:10.1006/jcis.1999.6654