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Hydrogel-Based Colloidal Polymeric System for Protein and Drug Delivery: Physical and Chemical Characterization, Permeability Control and Applications

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Filled Elastomers Drug Delivery Systems

Part of the book series: Advances in Polymer Science ((POLYMER,volume 160))

Abstract

The use of polymeric nanoparticles as drug carriers is receiving an increasing amount of attention both in academia and industry. The development of suitable delivery systems for protein drugs with high molecular weights and short half-lives is of current interest. In addition, nanoparticles have a number of potential applications in drug and vaccine delivery as well as gene therapy applications. This article features a new production technology for nanoparticles comprised of multicomponent polymeric complexes that are candidates for delivery vehicles of biological molecules such as proteins and drugs. Materials science theory and practice provide the basis for the development of highly compacted structures that are insoluble in water and buffered media. Biocompatible and mostly natural polymers are fabricated into thermodynamically stable nanoparticles, in the absence of organic solvents, using two types of processing: batch and continuous. Careful choice of construction materials and the superposition of several interacting principles during their production allow for the customization of the physicochemical properties of the structures. Among the typical polymers used to assemble nanoparticles, different polysaccharides, natural amines and polyamines were investigated. The entrapped substances tested included proteins, antigens and small drug molecules. The size and charge of nanoparticles is considered to be of primary importance for application in biological systems. Detailed experiments in batch and continuous systems allowed time-dependent stoichiometric characterization of the production process and an understanding of fundamental assembly principles of such supramolecular structures. Continuous-flow production is shown to provide more consistent data in terms of product quality and consistency, with further possibilities of process development and commercialization. To control permeability, polydextran aldehyde, incorporated into the particle core, was used to enable physiologic cross-linking and long-term retention of substances that would otherwise rapidly leak out of the nanoparticles. Results of cross-linking experiments clearly demonstrated that the release rate could be substantially reduced, depending on the degree of cross-linking. For vaccine antigen delivery tests we measured an antibody production following subcutaneous and oral administration. The data indicated that only the cross-linked antigen was immunogenic when the oral route of administration was used. The data presented in this paper address primarily the utility of nanoparticulates for oral delivery of vaccine antigen. This novel technology is extensively discussed in contrast to other technologies, primarily water- and organic solvent-based. The usefulness is demonstrated using several examples, evaluating protein and small drug delivery.

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Authors and Affiliations

  1. 107 Olin Hall, Chemical Engineering Department, Vanderbilt University, 24th Avenue South & Garland Avenue, Nashville, TN, 37235, USA

    Ales Prokop & Evgenii Kozlov

  2. Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN, 37232-2561, USA

    Gianluca Carlesso & Jeffrey M. Davidson

  3. Department of Veterans Affairs Medical Center, Research Service, Nashville, TN, 37212-2637, USA

    Jeffrey M. Davidson

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  1. Ales Prokop
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  2. Evgenii Kozlov
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  3. Gianluca Carlesso
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  4. Jeffrey M. Davidson
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Prokop, A., Kozlov, E., Carlesso, G., Davidson, J.M. (2002). Hydrogel-Based Colloidal Polymeric System for Protein and Drug Delivery: Physical and Chemical Characterization, Permeability Control and Applications. In: Filled Elastomers Drug Delivery Systems. Advances in Polymer Science, vol 160. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-45362-8_3

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