Controlled release of therapeutics using interpenetrating polymeric networks

Aminabhavi, Tejraj M.; Nadagouda, Mallikarjuna N.; More, Uttam A.; Joshi, Shrinivas D.; Kulkarni, Vaishali; Noolvi, Malleshappa N.; Kulkarni, P. V.

doi:10.1517/17425247.2014.974871

Cited by 64 publications

(37 citation statements)

References 108 publications

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“…It was expected that if the NIPAAM monomer and PEGDA crosslinker were polymerized in the presence of PEG in solution, that better PEG entanglement would be achieved than the analogous polymerization in the presence of the unmodified antibody. It was thought that PEG would form an interpenetrating polymer network with the PEGDA–NIPAAM network, which would result in slower diffusion of a PEGylated protein from the PEGDA crosslinked NIPAAM network than the unmodified protein (that is unable to become entangled in the hydrogel network). There would be better compatibility between the PEGDA crosslinked NIPAAM and PEG compared to the unmodified protein.…”

Section: Resultsmentioning

confidence: 99%

Comparative Study of In Situ Loaded Antibody and PEG‐Fab NIPAAM Gels

Awwad

Al-Shohani

Khaw

et al. 2017

Macromolecular Bioscience

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Hydrogels can potentially prolong the release of a therapeutic protein, especially to treat blinding conditions. One challenge is to ensure that the protein and hydrogel are intimately mixed by better protein entanglement within the hydrogel. N-isopropylacrylamide (NIPAAM) gels are optimized with poly(ethylene glycol) diacrylate (PEDGA) crosslinker in the presence of either bevacizumab or PEG conjugated ranibizumab (PEG -Fab ). The release profiles of the hydrogels are evaluated using an outflow model of the eye, which is previously validated for human clearance of proteins. Release kinetics of in situ loaded bevacizumab-NIPAAM gels displays a prolonged bimodal release profile in phosphate buffered saline compared to bevacizumab loaded into a preformed NIPAAM gel. Bevacizumab release in simulated vitreous from in situ loaded gels is similar to bevacizumab control indicating that diffusion through the vitreous rather than from the gel is rate limiting. Ranibizumab is site-specifically PEGylated by disulfide rebridging conjugation. Prolonged and continuous release is observed with the in situ loaded PEG -Fab -NIPAAM gels compared to PEG -Fab injection (control). Compared to an unmodified protein, there is better mixing due to PEG entanglement and compatibility of PEG -Fab within the NIPAAM-PEDGA hydrogel. These encouraging results suggest that the extended release of PEGylated proteins in the vitreous can be achieved using injectable hydrogels.

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Section: Resultsmentioning

confidence: 99%

Comparative Study of In Situ Loaded Antibody and PEG‐Fab NIPAAM Gels

Awwad

Al-Shohani

Khaw

et al. 2017

Macromolecular Bioscience

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“…Hydrogels are prepared from hydrophilic polymers with a threedimensional (3D) network that are capable of uptaking large volumes of water without dissolving. [1][2][3] In particular, stimuliresponsive hydrogels, also termed intelligent hydrogels, which can undergo a reversible phase transition in response to a great deal of external stimuli including temperature, 4 light, 5 pH, 6 electric eld, 7 have attracted considerable attention in medical and biological applications. 8,9 Of these intelligent hydrogel materials, the pH-responsive ones are widely investigated because the pH value is a crucial environmental factor in human bodies.…”

Section: Introductionmentioning

confidence: 99%

Cationic Salecan-based hydrogels for release of 5-fluorouracil

Wei

et al. 2017

RSC Adv.

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“…To elongate the shelf-life, a combination of plasticizers like glycerol:sorbitol [44] and glycerol:sucrose [45] were studied. To prepare IPNFs, additional to the mixture described above, 0.5 wt % one of PVA [38,46], PEG [47] or HEC [48] was added as shown in Table 1. The resulting solution was than casted on circular templates (8 mm diameter) and left at ambient conditions to dry for 24 h. The dried films were then peeled off (8 mm diameter ×100 μm thickness) and dipped in GA aqueous solutions of different volume ratios (0.1, 0.25, 0.5, and 1 vol %) for 6 h at 4 °C to cross-link.…”

Section: Methodsmentioning

confidence: 99%

Transient Biocompatible Polymeric Platforms for Long-Term Controlled Release of Therapeutic Proteins and Vaccines

et al. 2016

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Abstract:Polymer-based interpenetrating networks (IPNs) with controllable and programmable degradation and release kinetics enable unique opportunities for physisorption and controlled release of therapeutic proteins or vaccines while their chemical and structural integrities are conserved. This paper presents materials, a simple preparation method, and release kinetics of a series of long-term programmable, biocompatible, and biodegradable polymer-based IPN controlled release platforms. Release kinetics of the gp41 protein was controlled over a 30-day period via tuning and altering the chemical structure of the IPN platforms. Post-release analysis confirmed structural conservation of the gp41 protein throughout the process. Cell viability assay confirmed biocompatibility and non-cytotoxicity of the IPNs.

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Controlled release of therapeutics using interpenetrating polymeric networks

Cited by 64 publications

References 108 publications

Comparative Study of In Situ Loaded Antibody and PEG‐Fab NIPAAM Gels

Comparative Study of In Situ Loaded Antibody and PEG‐Fab NIPAAM Gels

Cationic Salecan-based hydrogels for release of 5-fluorouracil

Transient Biocompatible Polymeric Platforms for Long-Term Controlled Release of Therapeutic Proteins and Vaccines

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