Microfluidic fabrication of monodisperse microcapsules for glucose-response at physiological temperature

Hydrogel-based hollow microcapsules with good monodispersity and repeated glucose-response under physiological temperature and glucose concentration conditions have been fabricated by a simple emulsion-template approach. Double emulsions from microfluidic devices are used as templates to synthesize the monodisperse glucose-responsive microcapsules. In the poly(N-isopropylacrylamide-co-3-aminophenylboronic acid-co-acrylic acid) (P(NIPAM-co-AAPBA-co-AAc)) hydrogel shell of the microcapsules, the thermo-responsive PNIPAM network and the glucose-responsive AAPBA moiety are respectively used for actuation and glucose response, and the AAc moiety is used for adjusting the volume phase transition temperature of the shell. Glucose-responsive microcapsules prepared with 2.4 mol% AAc exhibit reversible and repeated swelling/shrinking response to glucose concentration changes within the physiological blood glucose concentration range (0.4–4.5 g L−1) at 37 °C. Rhodamine B and fluorescein-isothiocyanate-labeled insulin are used as model molecules and model drugs to demonstrate the potential application of the microcapsules for glucose-responsive controlled release. The microcapsules provide a promising and feasible model for developing glucose-responsive sensors and self-regulated delivery systems for diabetes and cancer therapy. Moreover, the microfluidic fabrication approach and research results presented here provide valuable guidance for the design and fabrication of monodisperse glucose-responsive microcapsules.

[1]  Kinam Park,et al.  Environment-sensitive hydrogels for drug delivery , 2001 .

[2]  G. Steil,et al.  Closed-loop insulin delivery – what lies between where we are and where we are going? , 2005, Expert opinion on drug delivery.

[3]  Yoshihiro Ito,et al.  pH-Sensitive Gating by Conformational Change of a Polypeptide Brush Grafted onto a Porous Polymer Membrane , 1997 .

[4]  J. Anzai,et al.  Ortho-azo substituted phenylboronic acids for colorimetric sugar sensors. , 2007, Bioorganic & medicinal chemistry letters.

[5]  V. Ravaine,et al.  Monodispersed glucose-responsive microgels operating at physiological salinity. , 2006, Biomacromolecules.

[6]  V. Ganapathy,et al.  Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. , 2009, Pharmacology & therapeutics.

[7]  Wei Qi,et al.  Fabrication of glucose-sensitive protein microcapsules and their applications , 2011 .

[8]  L. Lyon,et al.  Soft Nanotechnology with Soft Nanoparticles , 2006 .

[9]  S. Ravaine,et al.  Multiresponsive hybrid microgels and hollow capsules with a layered structure. , 2009, Langmuir : the ACS journal of surfaces and colloids.

[10]  T. Okano,et al.  Totally Synthetic Polymer Gels Responding to External Glucose Concentration: Their Preparation and Application to On−Off Regulation of Insulin Release , 1998 .

[11]  T. Jones,et al.  Forming concentric double-emulsion droplets using electric fields , 2009 .

[12]  S. Patil,et al.  Glucose-triggered drug delivery from borate mediated layer-by-layer self-assembly. , 2010, ACS applied materials & interfaces.

[13]  L. Chu Controlled release systems for insulin delivery , 2005 .

[14]  Wei Wang,et al.  A novel thermo-induced self-bursting microcapsule with magnetic-targeting property. , 2009, Chemphyschem : a European journal of chemical physics and physical chemistry.

[15]  G. Sukhorukov,et al.  Polymer Microcapsules with Carbohydrate‐Sensitive Properties , 2008 .

[16]  T. Okano,et al.  A novel drug delivery system utilizing a glucose responsive polymer complex between poly (vinyl alcohol) and poly (N-vinyl-2-pyrrolidone) with a phenylboronic acid moiety , 1992 .

[17]  Liang-Yin Chu,et al.  Smart thermo-triggered squirting capsules for nanoparticle delivery , 2010 .

[18]  K. Kataoka,et al.  Glucose-responsive polymer bearing a novel phenylborate derivative as a glucose-sensing moiety operating at physiological pH conditions. , 2003, Biomacromolecules.

[19]  N. Peppas Is there a future in glucose-sensitive, responsive insulin delivery systems? , 2004 .

[20]  T. Okano,et al.  Amine containing phenylboronic acid gel for glucose-responsive insulin release under physiological pH , 1995 .

[21]  Teruo Okano,et al.  Sensitive glucose-induced change of the lower critical solution temperature of poly [N,N-dimethylacrylamide-co-3-(acrylamido) phenyl-boronic acid] in physiological saline , 1994 .

[22]  G. Whitesides The origins and the future of microfluidics , 2006, Nature.

[23]  Wei Wang,et al.  Monodisperse core-shell chitosan microcapsules for pH-responsive burst release of hydrophobic drugs , 2011 .

[24]  Igor K Lednev,et al.  High ionic strength glucose-sensing photonic crystal. , 2003, Analytical chemistry.

[25]  Liang-Yin Chu,et al.  Preparation of glucose-sensitive microcapsules with a porous membrane and functional gates. , 2004, Colloids and surfaces. B, Biointerfaces.

[26]  B. Catargi,et al.  Glucose-responsive microgels with a core-shell structure. , 2008, Journal of Colloid and Interface Science.

[27]  P. Pedersen,et al.  Glucose catabolism in cancer cells: regulation of the type II hexokinase promoter by glucose and cyclic AMP , 1996, FEBS letters.

[28]  Yongjun Zhang,et al.  Synthesis and volume phase transitions of glucose-sensitive microgels. , 2006, Biomacromolecules.

[29]  Liang-Yin Chu,et al.  Controllable monodisperse multiple emulsions. , 2007, Angewandte Chemie.

[30]  D. Cui,et al.  A pH-, thermo-, and glucose-, triple-responsive hydrogels: Synthesis and controlled drug delivery , 2010 .

[31]  Shigehiro Takahashi,et al.  Layer-by-layer construction of protein architectures through avidin–biotin and lectin–sugar interactions for biosensor applications , 2012, Analytical and Bioanalytical Chemistry.

[32]  T. Miyata,et al.  Biomolecule-sensitive hydrogels. , 2002, Advanced drug delivery reviews.

[33]  Jie Zhang,et al.  Poly(N-isopropylacrylamide)-based comb-type grafted hydrogel with rapid response to blood glucose concentration change at physiological temperature , 2008 .

[34]  R Langer,et al.  Responsive polymeric delivery systems. , 2001, Advanced drug delivery reviews.

[35]  A. Jonas,et al.  Glucose-responsive polyelectrolyte capsules. , 2006, Langmuir : the ACS journal of surfaces and colloids.

[36]  D. Weitz,et al.  Monodisperse Double Emulsions Generated from a Microcapillary Device , 2005, Science.

[37]  L. Chu,et al.  Thermo-responsive monodisperse core-shell microspheres with PNIPAM core and biocompatible porous ethyl cellulose shell embedded with PNIPAM gates. , 2012, Journal of colloid and interface science.

[38]  Yongjun Zhang,et al.  Drug release kinetics from monolayer films of glucose-sensitive microgel , 2010 .

[39]  M. Taylor,et al.  The effect of degree of acrylic derivatisation on dextran and concanavalin A glucose-responsive materials for closed-loop insulin delivery. , 2006, Biomaterials.

[40]  Robert Pelton,et al.  Engineering Glucose Swelling Responses in Poly(N-isopropylacrylamide)-Based Microgels , 2007 .

[41]  Akira Matsumoto,et al.  Glucose-responsive polymer gel bearing phenylborate derivative as a glucose-sensing moiety operating at the physiological pH. , 2004, Biomacromolecules.

[42]  Haiting Shi,et al.  Sugar-installed thermoresponsive micellar aggregates self-assembled from “coil-comb-coil” triblock glycopolymers: preparation and recognition with Concanavalin A , 2012 .

[43]  Wei Wang,et al.  Controllable microfluidic production of multicomponent multiple emulsions. , 2011, Lab on a chip.

[44]  Shigehiro Takahashi,et al.  Phenylboronic acid monolayer-modified electrodes sensitive to sugars. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[45]  Mikito Yasuzawa,et al.  Fabrication of an Implantable Fine Needle-Type Glucose Sensor Using γ-Polyglutamic Acid , 2010 .

[46]  Wanzhi. Wei,et al.  Carbon nanotube/chitosan/gold nanoparticles-based glucose biosensor prepared by a layer-by-layer technique , 2009 .

[47]  Yue Cui,et al.  Triggered release of insulin from glucose-sensitive enzyme multilayer shells. , 2009, Biomaterials.