Controlled Release of Interleukin-2 from Biodegradable Microspheres

Hora, Maninder; Rana, Rajsharan K.; Nunberg, Jack H.; Tice, Thomas R.; Gilley, Richard M.; Hudson, Michael E.

doi:10.1038/nbt0890-755

Cited by 82 publications

(28 citation statements)

References 22 publications

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“…The incomplete recovery of the encapsulated IL-2 may be attributed to IL-2 precipitation in the absence of sufficient quantities of agents to stabilize the protein resolubilization as well as possible protein interaction with the polymer matrix. 40 The DE formulation released active IL-2 for >1 month, whereas the IL-2 released from the SE microspheres was completely inactive by 3 weeks. In both cases, inactive protein release continued beyond the duration of release of active protein.…”

Section: Discussionmentioning

confidence: 99%

Microparticulate Formulations for the Controlled Release of Interleukin-2

Thomas

Kohane

Wang

et al. 2004

Journal of Pharmaceutical Sciences

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Section: Discussionmentioning

confidence: 99%

Microparticulate Formulations for the Controlled Release of Interleukin-2

Thomas

Kohane

Wang

et al. 2004

Journal of Pharmaceutical Sciences

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“…40 Previous investigators have attempted to incorporate polypeptides into PLGA microspheres with variable success. Some of the polypeptides used include nerve growth factor, 12,14,18-21 ␣-, ␤-, and ␥-interferon, 17,22-24 growth hormone, 16,17,25 insulin, 32 erythropoietin, 21 transforming growth factor-␤, 29 epidermal growth factor, 27 interlukin-2, 30 basic fibroblast growth factor, 28 and VEGF. 15,26 In this investigation, biodegradable PLGA/ PEG microspheres were used to develop a system capable of releasing bioactive proteins.…”

Section: Discussionmentioning

confidence: 99%

Development andin vitro characterization of vascular endothelial growth factor (VEGF)-loaded poly(DL-lactic-co-glycolic acid)/poly(ethylene glycol) microspheres using a solid encapsulation/single emulsion/solvent extraction technique

King

Patrick

2000

J. Biomed. Mater. Res.

166

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Poly(DL-lactide-co-glycolide) (PLGA)/polyethylene glycol (PEG) microspheres are one modality of controlled delivery of biologically active molecules that would further the development of engineered tissues. As a possible mechanism to stimulate angiogenesis within an engineered tissue, vascular endothelial growth factor (VEGF) and bovine serum albumin (BSA) were coencapsulated into microspheres fabricated from PEG and 50/50 PLGA using a solid-encapsulation/single-emulsion/solvent extraction technique. Two VEGF/BSA ratios were studied: 1:2000 and 1:10,000. Analysis consisted of the loading efficiency, particle size distribution, bright-field microscopy, scanning electron microscopy, release kinetics, and an in vitro human umbilical vein endothelial cell proliferation assay to assess biological activity of the released VEGF. Results show the microspheres could be manufactured, stored, and degraded over 28 days. The burst release rates for 1:2000 and 1:10,000 VEGF/BSA microspheres were 71.87 +/- 8.11 and 27.91 +/- 1.71 ng/mL (mean +/- standard error of the mean), respectively; steady-state release rates were 6.56 +/- 1.10 and 2.21 +/- 0.47 ng/mL, respectively. The microspheres released biologically active VEGF, and the VEGF increased the proliferation of HUVECs in culture (p <.05). The successful development of a novel, cost-effective, scalable technique for producing microspheres loaded with biologically active proteins is presented. Using the data obtained from these studies, a defined concentration of microspheres will deliver a quantifiable level of VEGF at a known release rate.

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“…It is proposed that Spantide II can be formulated as a stable topical agent that provides adequate skin permeability for the treatment of inflammatory skin disorders such as dermatitis and psoriasis. Various delivery systems, such as liposomes, 5 biodegradable microspheres, 6,7 and hydrogels 8 have been investigated in order to circumvent the susceptibility of peptides to degradation during formulation, storage, and administration. Proteins and peptides are compatible with hydrogels, such as nonionic cellulose polymers and poloxamer gels, which are nontoxic and exhibit reversible thermal characteristics.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo evaluation of topical formulations of Spantide II

et al. 2005

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The purpose of this study was to develop and evaluate topical formulations of Spantide II, a neurokinin-1 receptor (NK-1R) antagonist, for the treatment of inflammatory skin disorders. Spantide II lotion and gel was formulated with and without n-methyl-2-pyrrolidone (NMP) as a penetration enhancer. The release of Spantide II from gels was evaluated using microporous polyethylene and polypropylene membranes in a Franz Diffusion cell setup. In vitro percutaneous absorption of Spantide II from lotion and gel formulations was evaluated using the above setup by replacing the membranes with hairless rat skin. The in vivo anti-inflammatory activity of Spantide II formulations was evaluated in an allergic contact dermatitis (ACD) mouse model. Among different gels studied, PF127 gel showed highest (70-fold) release of Spantide II compared with hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) gels. Lotion and gel formulations with or without NMP showed no detectable levels of Spantide II in the receiver compartment of the Franz diffusion cell until 24 hours. However, Spantide II showed significant retention in epidermis and dermis from lotion and gel formulations at 24 hours. The dermal levels increased~3.5-and 2-fold when the lotion and gel formulations contained NMP as compared with the formulation with no NMP (P G .05). The in vivo studies indicated that Spantide II formulations with NMP were effective in significantly reducing ACD response, similar to dexamethasone (0.5 mM). In conclusion, Spantide II was stable as a topical formulation and delivered to target skin tissue (epidermis and dermis) for the treatment of ACD. In addition this study supports the role of cutaneous neurosensory system in modulating inflammatory responses in the skin.

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Controlled Release of Interleukin-2 from Biodegradable Microspheres

Cited by 82 publications

References 22 publications

Microparticulate Formulations for the Controlled Release of Interleukin-2

Microparticulate Formulations for the Controlled Release of Interleukin-2

Development andin vitro characterization of vascular endothelial growth factor (VEGF)-loaded poly(DL-lactic-co-glycolic acid)/poly(ethylene glycol) microspheres using a solid encapsulation/single emulsion/solvent extraction technique

In vitro and in vivo evaluation of topical formulations of Spantide II

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