Smart polymers for responsive drug-delivery systems

The rapid advancement of biomedical research has led to many creative applications for biocompatible polymers. As modern medicine discerns more mechanisms, both of physiology and of pathophysiology, the approach to healing is to mimic, or if possible, to recreate the physiology of healthy functioning. Thus, the area of smart polymers for responsive drug delivery has evolved. The developments fall under two categories: externally regulated or pulsatile systems (also known as 'open-loop' systems) and self-regulated systems (also known as 'closed-loop'). The externally controlled devices apply external triggers for pulsatile delivery such as: ultrasonic, magnetic, electric, light and chemical or biochemical agents. The self-regulated systems, on the other hand, are defined as systems where the controlled variable is detected, and as a result, the system output is adjusted accordingly. The release rate is controlled by feedback information, without any external intervention. The self-regulated systems utilize several approaches for the rate control mechanisms such as thermal, pH-sensitive polymers, enzyme–substrate reactions, pH-sensitive drug solubility, competitive binding, antibody interactions and metal-concentration-dependent hydrolysis.

[1]  Joseph Kost,et al.  On-demand release by ultrasound from osmotically swollen hydrophobic matrices. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[2]  N. Brandon,et al.  GABAA-receptor-associated protein links GABAA receptors and the cytoskeleton , 1999, Nature.

[3]  T. Okano,et al.  Photo-responsive degradation of heterogeneous hydrogels comprising crosslinked hyaluronic acid and lipid microspheres for temporal drug delivery , 1993 .

[4]  S. W. Kim,et al.  Self-regulated glycosylated insulin delivery , 1990 .

[5]  D. Wirtz,et al.  Reversible hydrogels from self-assembling artificial proteins. , 1998, Science.

[6]  B Mattiasson,et al.  'Smart' polymers and what they could do in biotechnology and medicine. , 1999, Trends in biotechnology.

[7]  Robert Langer,et al.  Small-scale systems for in vivo drug delivery , 2003, Nature Biotechnology.

[8]  J. Kost,et al.  Ultrasound-enhanced polymer degradation and release of incorporated substances. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Kost Pulsed and Self-Regulated Drug Delivery , 1990 .

[10]  Kinam Park,et al.  Modulated insulin delivery from glucose-sensitive hydrogel dosage forms. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[11]  Pulsed polymers , 2003, Nature materials.

[12]  K. Nguyen,et al.  Development of a Temperature‐Sensitive Composite Hydrogel for Drug Delivery Applications , 2006, Biotechnology progress.

[13]  V. Calhoun,et al.  Controlled release of bioactive materials. , 1980 .

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

[15]  Robert Langer,et al.  Multi-pulse drug delivery from a resorbable polymeric microchip device , 2003, Nature materials.

[16]  J. Kost,et al.  Magnetically enhanced insulin release in diabetic rats. , 1987, Journal of biomedical materials research.

[17]  R Langer,et al.  Characterization of glucose-mediated insulin release from implantable polymers. , 1996, Journal of pharmaceutical sciences.

[18]  K. Ishihara,et al.  Control of insulin permeation through a polymer membrane with responsive function for glucose , 1983 .

[19]  C. Alexander,et al.  Stimuli responsive polymers for biomedical applications. , 2005, Chemical Society reviews.

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

[21]  Kinam Park,et al.  Controlled drug delivery : challenges and strategies , 1997 .

[22]  R. Langer,et al.  Drug delivery and targeting. , 1998, Nature.

[23]  Y. Cohen,et al.  Characterization of glucose-sensitive insulin release systems in simulated in vivo conditions. , 2000, Biomaterials.

[24]  E. Edelman,et al.  Regulation of drug release from polymer matrices by oscillating magnetic fields. , 1985, Journal of biomedical materials research.

[25]  G. Nakayama,et al.  A study of reversibly inactivated lipases for use in a morphine-triggered naltrexone delivery system. , 1995, Journal of biomedical materials research.

[26]  Y. Osada,et al.  A polymer gel with electrically driven motility , 1992, Nature.

[27]  C. Alexander Temperature- and pH-responsive smart polymers for gene delivery , 2006, Expert opinion on drug delivery.

[28]  Liang-Yin Chu,et al.  Control of pore size and permeability of a glucose-responsive gating membrane for insulin delivery. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[29]  Ronald A Siegel,et al.  New mode of drug delivery: long term autonomous rhythmic hormone release across a hydrogel membrane. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[30]  S. Mitragotri,et al.  Low-frequency sonophoresis: a review. , 2004, Advanced drug delivery reviews.

[31]  Samarth Kulkarni,et al.  Photoresponsive polymer–enzyme switches , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  James P Cox,et al.  Drug release from pH-responsive thermogelling pentablock copolymers. , 2007, Journal of biomedical materials research. Part A.

[33]  R. Langer,et al.  Enzymatically controlled drug delivery. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[34]  B. Ratner,et al.  Self-assembled molecular structures as ultrasonically-responsive barrier membranes for pulsatile drug delivery. , 2001, Journal of biomedical materials research.

[35]  N A Peppas,et al.  Glucose-sensitivity of glucose oxidase-containing cationic copolymer hydrogels having poly(ethylene glycol) grafts. , 2000, Journal of Controlled Release.

[36]  J. Kost,et al.  Magnetically controlled release systems: effect of polymer composition. , 1985, Journal of biomedical materials research.

[37]  Nili Grossman,et al.  The nature of ultrasound-SLS synergism during enhanced transdermal transport. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[38]  External control of drug release: controlled release of insulin from a hydrophilic polymer implant by ultrasound irradiation in diabetic rats , 1988, The Journal of pharmacy and pharmacology.

[39]  Y. Bae,et al.  Electrically credible polymer gel for controlled release of drugs , 1991, Nature.

[40]  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 .

[41]  Yoshihito Osada,et al.  Polymer gels as soft and wet chemomechanical systems—an approach to artificial muscles , 2002 .

[42]  Sakurai Yasuhisa,et al.  Inflammation responsive degradation of crosslinked hyaluronic acid gels , 1992 .

[43]  J. Heller,et al.  Controlled drug release by polymer dissolution. II: Enzyme-mediated delivery device. , 1979, Journal of pharmaceutical sciences.

[44]  J. Kost,et al.  Calcium Responsive Bioerodible Drug Delivery System , 1999, Pharmaceutical Research.

[45]  R. Langer,et al.  Light-induced shape-memory polymers , 2005, Nature.

[46]  M. Cima,et al.  A controlled-release microchip , 1999, Nature.

[47]  Joseph Kost,et al.  Enzymatically controlled responsive drug delivery systems , 2002 .

[48]  Jindrich Kopecek,et al.  Smart and genetically engineered biomaterials and drug delivery systems. , 2003, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[49]  Toyoichi Tanaka,et al.  Phase transition in polymer gels induced by visible light , 1990, Nature.

[50]  R. Langer,et al.  Where a pill won't reach. , 2003, Scientific American.

[51]  Masahiro Irie,et al.  Photoinduced phase transition of gels , 1990 .

[52]  Kouichi Sutani,et al.  Intelligent type controlled release systems by radiation techniques , 1999 .

[53]  M. Madou,et al.  Genetically engineered protein in hydrogels tailors stimuli-responsive characteristics , 2005, Nature Materials.

[54]  A. Cerami,et al.  A glucose-controlled insulin-delivery system: semisynthetic insulin bound to lectin. , 1979, Science.

[55]  M. Prato,et al.  Applications of carbon nanotubes in drug delivery. , 2005, Current opinion in chemical biology.

[56]  A. M. Vinogradov,et al.  Ultrasonically Controlled Release of Ciprofloxacin from Self-Assembled Coatings on Poly(2-Hydroxyethyl Methacrylate) Hydrogels for Pseudomonas aeruginosa Biofilm Prevention , 2005, Antimicrobial Agents and Chemotherapy.

[57]  B. Ratner,et al.  Surface modification of polymers with self-assembled molecular structures: multitechnique surface characterization. , 2000, Biomacromolecules.

[58]  R. Langer,et al.  Magnetic modulation of release of macromolecules from polymers. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[59]  Takashi Miyata,et al.  A reversibly antigen-responsive hydrogel , 1999, Nature.

[60]  S. Mitragotri,et al.  Current status and future potential of transdermal drug delivery , 2004, Nature Reviews Drug Discovery.

[61]  E. Edelman,et al.  In vitro and in vivo kinetics of regulated drug release from polymer matrices by oscillating magnetic fields. , 1987, Journal of biomedical materials research.

[62]  D. Schmaljohann Thermo- and pH-responsive polymers in drug delivery. , 2006, Advanced drug delivery reviews.

[63]  M. Madou,et al.  Polymer actuator valves toward controlled drug delivery application. , 2006, Biosensors & bioelectronics.