Abstract

Novel carriers for controlled delivery of drugs are prepared from hydrogels that have the ability to respond to pH, ionic strength, composition of physiological solution and temperature. Such hydrogels can be used for abrupt release of drugs or proteins at constant rates. We propose to develop graft copolymers of poly(ethylene glycol) with poly(methacrylic acid), which can complex by hydrogen bonding. Upon loading these systems with drugs or proteins and upon abruptly changing the pH of the surrounding solution from acidic to basic it is possible to decomplex the network leading to sudden drug release. An alternative release system based on interpenetrating polymeric networks of complexing is also developed. Finally, pH-sensitive hydrogels of poly(hydroxyethyl acrylic acid) are synthesized in the presence of water at concentrations larger than the equilibrium concentrations of the corresponding gels. When these systems are loaded with drugs or proteins and swollen in constant pH solutions, they deswell (collapse) transforming the polymer system into a highly porous gel. Thus, the incorporated drugs can be released at constant rates. The release process is dependent on the pH and temperature of the solution. Experimental studies of drug release from such systems will be carried out and the overall release behavior will be model led.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM043337-04A1
Application #
2181964
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1989-12-01
Project End
1998-08-31
Budget Start
1994-09-01
Budget End
1995-08-31
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
Purdue University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
072051394
City
West Lafayette
State
IN
Country
United States
Zip Code
47907

  Publications

Sainz, Vanessa; Moura, Liane I F; Peres, Carina et al. (2018) ?-Galactosylceramide and peptide-based nano-vaccine synergistically induced a strong tumor suppressive effect in melanoma. Acta Biomater 76:193-207
Bae, Hojae; Puranik, Amey S; Gauvin, Robert et al. (2012) Building vascular networks. Sci Transl Med 4:160ps23
Liechty, William B; Caldorera-Moore, Mary; Phillips, Margaret A et al. (2011) Advanced molecular design of biopolymers for transmucosal and intracellular delivery of chemotherapeutic agents and biological therapeutics. J Control Release 155:119-27
Foss, Aaron C; Goto, Takahiro; Morishita, Mariko et al. (2004) Development of acrylic-based copolymers for oral insulin delivery. Eur J Pharm Biopharm 57:163-9
Torres-Lugo, Madeline; Garcia, Marcos; Record, Rae et al. (2002) pH-Sensitive hydrogels as gastrointestinal tract absorption enhancers: transport mechanisms of salmon calcitonin and other model molecules using the Caco-2 cell model. Biotechnol Prog 18:612-6
Baumgartner, Saia; Kristl, Julijana; Peppas, Nicholas A (2002) Network structure of cellulose ethers used in pharmaceutical applications during swelling and at equilibrium. Pharm Res 19:1084-90
Torres-Lugo, Madeline; Garcia, Marcos; Record, Rae et al. (2002) Physicochemical behavior and cytotoxic effects of p(methacrylic acid-g-ethylene glycol) nanospheres for oral delivery of proteins. J Control Release 80:197-205
Zhang, J; Peppas, N A (2002) Morphology of poly(methacrylic acid)/poly(N-isopropyl acrylamide) interpenetrating polymeric networks. J Biomater Sci Polym Ed 13:511-25
Peppas, Nicholas A; Huang, Yanbin (2002) Polymers and gels as molecular recognition agents. Pharm Res 19:578-87
Bures, P; Huang, Y; Oral, E et al. (2001) Surface modifications and molecular imprinting of polymers in medical and pharmaceutical applications. J Control Release 72:25-33

Showing the most recent 10 out of 21 publications