Drug and Protein Delivery

Our group originated and is the leading proponent of the use of hydrophilic polymers and hydrogels for the controlled delivery of drugs, peptides, and proteins. We have developed the new class of “swelling-controlled release systems,” which exhibit an unexpected time-dependent (zero-order) release due to coupling of diffusional and relaxational mechanisms. We were the first to propose and solve complex transport equations incorporating the viscoelastic behavior of the polymer and its relaxational behavior during swelling and drug release.

We continue working on the importance of two dimensionless numbers, the Swelling Interface number (Sw) and the Swelling Area number (Sa), in drug delivery as well as on improvement of the well-known exponential time dependence of the quantity of drug released, which has become a most desirable equation for the analysis of non-Fickian drug delivery.

A significant portion of our research addresses understanding of the release from pH-sensitive and temperature-sensitive swelling systems. We investigate the characteristics of pH-sensitive delivery, analyze the oscillatory behavior using Bolzman superposition analysis, study the influence of ionic strength and buffer composition on controlled release, and develop new delivery systems. Of particular interest is the work on insulin delivery using pH- and temperature-sensitive release systems.

We are investigating novel mucoadhesive systems for targeted delivery (for example, for buccal, nasal, and vaginal release).

More recently, and incollaboration with Profs. Mariko Morishita of Hoshi University and Anthony Lowman of Drexel University, we have developed a dose-dependent, oral drug-delivery system that administers insulin through a gel composed of poly(methacrylic acid) (PMAA) and poly(ethylene glycol) (PEG). This is the first such system that has been shown to work via the oral route. Thus, diabetic patients can avoid the cumbersome continuous injections of insulin and, instead, use dose-dependent capsules. The new system, so far tested in diabetic rats and dogs, can overcome these barriers. In tests on over 250 rats and dogs that were given capsules containing microspheres of this PMAA/PEG graft copolymer carrier, bioavailability of up to 21% was determined.

Finally, similar systems are investigated for release of calcitonin in postmenopausal women suffering from osteoporosis, and interferon-beta for multiple sclerosis.

Our work is also addressing cellular aspects of oral drug delivery. We are investigating the paracellular and intracellular transport across CaCo-2 cells in an effort to identify better carriers for oral delivery.

Related publications

J.O. Blanchette and N.A. Peppas, “Nanotechnology and Cancer Therapy” in N.A. Peppas, J.Z. Hilt and J.B. Thomas, eds, Nanotechnology in Therapeutics: Current Technology and Applications, 287-313, Horizon Press, Norfolk, UK, 2007.

N. J. Kavimandan, E. Losi, J. J. Wilson, J. S. Brodbelt and N. A. Peppas, “Synthesis and Characterization of Insulin-Transferrin Conjugates”, Bioconjugate Chem., 17, 1376-1384 (2006). [PDF Reprint]

M. Morishita and N. A. Peppas, “Is the Oral Route Possible for Peptide and Protein Drug Delivery?”, Drug Discovery Today, 11, 905- 910 (2006). [PDF Reprint]

N. J. Kavimandan, E. Losi, and N. A. Peppas, “Novel Delivery System Based on Complexation Hydrogels as Delivery Vehicles for Insulin-Transferrin Conjugates”, Biomaterials, 27, 3846-3854 (2006). [PDF Reprint]

M. Fukuda, N. A. Peppas and J. W. McGinity, “Properties of Sustained Release Hot-melt Extruded Tablets Containing Chitosan and Xanthan Gum”, Intern. J. Pharm., 310, 90-100 (2006). [PDF Reprint]

S. Venkatesh, M. E. Byrne, N. A. Peppas and J. Z. Hilt, “Applications of Biomimetic Systems in Drug Delivery”, Expert Opin. Drug Deliv., 2, 1085-1096 (2005).

J. O. Blanchette and N. A. Peppas, “Cellular Evaluation of Oral Chemotherapy Carriers”, J. Biomed. Mater. Res., 72A, 381-388 (2005). [PDF Reprint]

N.A. Peppas, “Is There a Future in Glucose-sensitive, Responsive Insulin Delivery?”, J. Drug Deliv. Sci. Techn., 14, 247-256 (2004). [PDF Reprint]

A.C. Foss and N.A. Peppas, “Investigation of the Cytotoxicity and Insulin Transport of Acrylic-based Copolymer Protein Delivery Systems in Contact with Caco-2 Cultures,” Europ. J. Pharm. Biopharm.., 57, 447-455 (2004). [PDF Reprint]

M. Torres-Lugo, M. García, R. Record and N.A. Peppas, “pH-Sensitive Hydrogels as Gastrointestinal Tract Absorption Enhancers: Transport Mechanisms of Salmon Calcitonin and Other Model Molecules using the Caco-2 Cell Model,” Biotechnology Progress, 18, 612-616 (2002). [PDF Reprint]

N.A. Peppas and A.M. Lowman, "Protein Delivery from Novel Bioadhesive Complexation Hydrogels," S. Frøkjaer, L. Christrup and P. Krogsgaard-Larsen, eds., Peptide and Protein Drug Delivery, 206-216, Munksgaard, Copenhagen, 1998.

J.H. Ward and N.A. Peppas, “Kinetic Gelation Modeling of Controlled Radical Polymerization,” Macromolecules, 33, 5137-5142 (2000). [PDF Reprint]

M.T. am Ende, D. Hariharan and N.A. Peppas, "Factors Influencing Drug and Protein Transport and Release from Ionic Hydrogels," Reactive Polymers, 25 , 127-137 (1995).

N.A. Peppas, "Hydrogels and Drug Delivery," Curr. Opinion Coll. Interfac. Sci., 2, 531-537 (1997).

C.L. Bell and N.A. Peppas, "Water, Solute and Protein Diffusion in Physiologically-Responsive Hydrogels of Poly(methacrylic acid-g-ethylene glycol)," Biomaterials, 17, 1203-1218 (1996). [PDF Reprint]

N.A. Peppas and A.R. Khare, "Preparation, Structure and Diffusional Behavior of Hydrogels in Controlled Release," Adv. Drug Deliv. Revs., 11, 1-35 (1993). [PDF Reprint]

P. Colombo, P.L. Catellani, N.A. Peppas, L. Maggi and U. Conte, "Swelling Characteristics of Hydrophilic Matrices for Controlled Release: New Dimensionless Number to Describe the Swelling and Release Behavior," Intern. J. Pharm., 88, 99-109 (1992). [PDF Reprint]

N.A. Peppas and J. Klier, "Controlled Release by Using Poly(ethylene oxide-g-methacrylic acid) Hydrogels,"J. Controlled Release, 16, 203-214 (1991). [PDF Reprint]

R.S. Langer and N.A. Peppas: "Chemical and Physical Structure of Polymers as Carriers for Controlled Release of Bioactive Agents: A Review," J. Macrom. Sci., Revs. Macromol. Chem. Phys., C23, 61-126 (1983).

C.T. Reinhart, R.W. Korsmeyer and N.A. Peppas: "Macromolecular Network Structure and its Effects on Drug and Protein Diffusion," Intern. J. Pharm. Techn., 2(2), 9-16 (1981).

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