Water Soluble Polymersfor Immunoisolation I: Complex Coacervation and Cytotoxicity

Prokop, Andreas; Hunkeler, David; DiMari, Samuel J.; Haralson, Michael A.; Wang, T. G.

doi:10.1007/3-540-69682-2_1

Cited by 79 publications

(52 citation statements)

References 48 publications

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“…48 Compared to PLL, chitosan binds alginate in an almost irreversible manner. 52,115 Thus, its application in cell encapsulation could elicit decreased inflammation and fibrotic responses, since the amount of polycation released from the capsules would be negligible. 96 Permeability of the capsules to protein could be reduced when chitosan M w and the degree of acetylation are increased.…”

Section: Coating Of Microbeadsmentioning

confidence: 99%

“…81 Sequential steps in PE shell preparation do not necessarily reflect real surface chemistry. Aside from the shielding strategy, the other way around is to use alternative polycations like PEI, 52,53 poly-L-ornithine [93][94][95] and poly(vinylamine). 114 However, further studies are needed to confirm the real efficacy and biocompatibility of these polymers.…”

Section: Coating Of Microbeadsmentioning

confidence: 99%

“…50 Seventy-five synthetic, semi-synthetic, and natural PEs have been tested by Prokop et al in a systematic approach to evaluate over 1000 complex coacervates. 52,53 A wide spectrum of polymers was investigated in several steps for cytotoxicity, gel strength, capsule resistance, permeability, and physical characteristics. These authors found that the optimal inner polymer must be a highly-charged polyanion with a M w of 10 kDa.…”

Section: 44mentioning

confidence: 99%

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Progress technology in microencapsulation methods for cell therapy

Rabanel

Banquy

Zouaoui

et al. 2009

Biotechnology Progress

122

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Cell encapsulation in microcapsules allows the in situ delivery of secreted proteins to treat different pathological conditions. Spherical microcapsules offer optimal surface-to-volume ratio for protein and nutrient diffusion, and thus, cell viability. This technology permits cell survival along with protein secretion activity upon appropriate host stimuli without the deleterious effects of immunosuppressant drugs. Microcapsules can be classified in 3 categories: matrix-core/shell microcapsules, liquid-core/shell microcapsules, and cells-core/shell microcapsules (or conformal coating). Many preparation techniques using natural or synthetic polymers as well as inorganic compounds have been reported. Matrix-core/shell microcapsules in which cells are hydrogel-embedded, exemplified by alginates capsule, is by far the most studied method. Numerous refinement of the technique have been proposed over the years such as better material characterization and purification, improvements in microbead generation methods, and new microbeads coating techniques. Other approaches, based on liquid-core capsules showed improved protein production and increased cell survival. But aside those more traditional techniques, new techniques are emerging in response to shortcomings of existing methods. More recently, direct cell aggregate coating have been proposed to minimize membrane thickness and implants size. Microcapsule performances are largely dictated by the physicochemical properties of the materials and the preparation techniques employed. Despite numerous promising pre-clinical results, at the present time each methods proposed need further improvements before reaching the clinical phase.

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Section: Coating Of Microbeadsmentioning

confidence: 99%

Section: Coating Of Microbeadsmentioning

confidence: 99%

Section: 44mentioning

confidence: 99%

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Progress technology in microencapsulation methods for cell therapy

Rabanel

Banquy

Zouaoui

et al. 2009

Biotechnology Progress

122

View full text Add to dashboard Cite

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“…Numerous water-soluble polymers for most acrylic derivatives and vinyl-type polymers have been investigated for use as macromolecular drug carriers, 29 biomaterials for cell and islet immunoisolation, 30 protein hybrids, 31 and advanced applications in biotechnology. 32 The random copolymers of VP-co-DMAm with selected monomer ratios exhibit a broad spectrum of physicochemical properties 23 and may be used for the preparation of controlled-release drug systems.…”

Section: Resultsmentioning

confidence: 99%

Drug complexation and physicochemical properties of vinylpyrrolidone‐N,N′‐dimethylacrylamide copolymers

Queiroz¹,

França²,

Abraham³

et al. 2004

J of Applied Polymer Sci

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Solid dispersions of the nonsteriodal antiinflammatory drug (NSAID) 2Ј,4Ј-difluoro-4-hydroxy-(1,1Ј-biphenyl)-3-carboxylic acid (DIF) with the water-soluble random copolymer poly(N-vinyl-2-pyrrolidone-co-N,NЈ-dimethylacrylamide) (VP-co-DMAm) were prepared by the solvent method (coevaporates) and melting DIF/VP-coDMAm (cofused) physical mixtures. Differential scanning calorimetry (DSC), infrared spectroscopy (FTIR), and X-ray diffraction (XRD) were used to elucidate the possible interaction between the NSAID drug and VP-co-DMAm in cofused and coevaporated polymer-drug solid dispersions. The XRD and FTIR studies suggest the presence of physical interactions with formation of a charge transfer complex between DIF and the VP-co-DMAm copolymers as a consequence of the coevaporation or cofusion processes. In solution, dynamic and equilibrium solubility studies were determined to elucidate the mechanism of interaction between DIF and VP-co-DMAm copolymers. Thermodynamics data about the DIF: VP-co-DMAm dissolution process indicate that the coevaporated systems are more stable that the cofused systems. The dissolution of the cofused and coevaporated systems was diffusion controlled and the dissolution kinetics followed the Noyes-Whitney and the Levich equations. Molecular simulations using semiempirical quantum chemical calculations reinforce the experimental results, suggesting that the improvement in the DIF solubility could be attributed to the charge transfer complex formation between the drug and VP-co-DMAm copolymers.

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“…The study was based on the use of ®ve rats per group per dose. Previously (Prokop et al, 1998), we established that it is meaningless to test individual polymeric components for their cytotoxicity in vitro. Polycations particularly exhibited substantial cytotoxicity over the practical range of concentrations.…”

Section: Compatibility and Animal Datamentioning

confidence: 99%

Water‐based nanoparticulate polymeric system for protein delivery: permeability control and vaccine application

Prokop

Kozlov

Newman

et al. 2002

Biotech & Bioengineering

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The idea of using polymeric nanoparticles as drug carriers is receiving an increasing amount of attention both in academia and industry, Nanoparticles have a number of potential applications in protein, drug and vaccine delivery, as well as gene therapy applications. In this article, we focus on this unique drug delivery technology as a method to control the release rate of substances, not only for protein delivery but also for delivering an experimental vaccine immunogen. Nanoparticles were assembled on the basis of ionic interaction between water-soluble polymers so that the resulting particles were stable in physiologic media. Among the typical polymers used to assemble nanoparticles, different polysaccharides, natural amines, and poly-amines were investigated. The entrapped substances tested included a protein and antigens. Polydextran aldehyde was incorporated into the particle core, to enable physiologic cross-linking as a method to control permeability. This resulted in 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 after 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 article address primarily the utility of nanoparticulates for oral delivery of vaccine antigen.

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Water Soluble Polymersfor Immunoisolation I: Complex Coacervation and Cytotoxicity

Cited by 79 publications

References 48 publications

Progress technology in microencapsulation methods for cell therapy

Progress technology in microencapsulation methods for cell therapy

Drug complexation and physicochemical properties of vinylpyrrolidone‐N,N′‐dimethylacrylamide copolymers

Water‐based nanoparticulate polymeric system for protein delivery: permeability control and vaccine application

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