Hydrogels for oral delivery of therapeutic proteins

In recent years there has been significant new interest in the development of transmucosal (mostly oral) pharmaceutical formulations for the delivery of therapeutic proteins. Emphasis has been given to the molecular design of new carriers for the delivery of insulin, calcitonin and various types of interferons for the treatment of diabetes, osteoporosis, multiple sclerosis and cancer. Most popular carriers include advanced designs of swollen hydrogels prepared from neutral or intelligent polymeric networks. In this review, the most successful of such systems are presented and their promise in the field described.

[1]  Nicholas A Peppas,et al.  Elucidation of the mechanism of incorporation of insulin in controlled release systems based on complexation polymers. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[2]  Nicholas A Peppas,et al.  Physicochemical behavior and cytotoxic effects of p(methacrylic acid-g-ethylene glycol) nanospheres for oral delivery of proteins. , 2002, Journal of controlled release : official journal of the Controlled Release Society.

[3]  M. Kipnes,et al.  Control of postprandial plasma glucose by an oral insulin product (HIM2) in patients with type 2 diabetes. , 2003, Diabetes care.

[4]  N. Platé,et al.  Mucoadhesive polymers with immobilized proteinase inhibitors for oral administration of protein drugs. , 2002, Biomaterials.

[5]  N. Peppas,et al.  Preparation and Characterization of pH-Responsive Poly(methacrylic acid-g-ethylene glycol) Nanospheres , 2002 .

[6]  Akira Yamamoto,et al.  Effects of Various Protease Inhibitors on the Intestinal Absorption and Degradation of Insulin in Rats , 1994, Pharmaceutical Research.

[7]  Robert Gurny,et al.  Structure and interactions in chitosan hydrogels formed by complexation or aggregation for biomedical applications. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[8]  Donald L. Wise,et al.  Handbook of Pharmaceutical Controlled Release Technology , 2000 .

[9]  N. Peppas,et al.  Investigation of interpolymer complexation in swollen polyelectolyte networks using solid‐state NMR spectroscopy , 2000 .

[10]  D. Wise.  Development of Acrylate and Methacrylate Polymer Networks for Controlled Release by Photopolymerization Technology , 2000 .

[11]  N. Peppas,et al.  Novel complexation hydrogels for oral peptide delivery: in vitro evaluation of their cytocompatibility and insulin-transport enhancing effects using Caco-2 cell monolayers. , 2003, Journal of biomedical materials research. Part A.

[12]  M. Torres-Lugo,et al.  Preparation and Characterization of P(MAA-g-EG) Nanospheres for Protein Delivery Applications , 2002 .

[13]  J. Gordon Still.  Development of oral insulin: progress and current status , 2002, Diabetes/metabolism research and reviews.

[14]  N. Peppas,et al.  Hydrogels in Pharmaceutical Formulations , 1999 .

[15]  A. Fasano,et al.  Modulation of intestinal tight junctions by Zonula occludens toxin permits enteral administration of insulin and other macromolecules in an animal model. , 1997, The Journal of clinical investigation.

[16]  N. Peppas,et al.  Oral delivery of insulin using pH-responsive complexation gels. , 1999, Journal of pharmaceutical sciences.

[17]  K.H.J. Buschow,et al.  Encyclopedia of Materials: Science and Technology , 2004 .

[18]  N. Peppas,et al.  Preparation of poly(methacrylic acid-g-poly(ethylene glycol)) nanospheres from methacrylic monomers for pharmaceutical applications. , 2002, International journal of pharmaceutics.

[19]  A. Bernkop‐Schnürch,et al.  Synthesis and In Vitro Evaluation of Chitosan-EDTA-Protease-Inhibitor Conjugates Which Might Be Useful in Oral Delivery of Peptides and Proteins , 1998, Pharmaceutical Research.

[20]  N. Peppas,et al.  Poly(ethylene glycol)-containing Hydrogels for Oral Protein Delivery Applications , 2003 .

[21]  N. Peppas,et al.  Molecular analysis of interpolymer complexation in graft copolymer networks , 2000 .

[22]  Nicholas A Peppas,et al.  Mucosal insulin delivery systems based on complexation polymer hydrogels: effect of particle size on insulin enteral absorption. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[23]  N. Peppas.  Gels for Drug Delivery , 2001 .

[24]  Nicholas A. Peppas.  Drug Delivery Biomaterials , 2001 .

[25]  D. Leckband,et al.  Direct Measurement of Interactions between Tethered Poly(ethylene glycol) Chains and Adsorbed Mucin Layers , 2002 .

[26]  F. Plakogiannis,et al.  Enhanced oral absorption of insulin from desolvated fatty acid-sodium glycocholate emulsions , 1994 .

[27]  N. Peppas,et al.  Transmucosal delivery systems for calcitonin: a review. , 2000, Biomaterials.

[28]  I. Gómez-Orellana,et al.  Challenges for the oral delivery of macromolecules , 2003, Nature Reviews Drug Discovery.

[29]  N. Peppas,et al.  Oral insulin delivery using P(MAA-g-EG) hydrogels: effects of network morphology on insulin delivery characteristics. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[30]  Nicholas A Peppas,et al.  pH‐Sensitive Hydrogels as Gastrointestinal Tract Absorption Enhancers: Transport Mechanisms of Salmon Calcitonin and Other Model Molecules Using the Caco‐2 Cell Model , 2002, Biotechnology progress.

[31]  N. Peppas,et al.  Structure and Interactions in Covalently and Ionically Crosslinked Chitosan Hydrogels for Biomedical Applications , 2003 .