Recombinant Human Bone Morphogenetic Protein-2 Binding and Incorporation in PLGA Microsphere Delivery Systems

Schrier, Jay A.; DeLuca, Patrick P.

doi:10.1081/pdt-100101400

Cited by 64 publications

(50 citation statements)

References 23 publications

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“…[1][2][3][4][5][6] Mucoadhesive polymers may fulfill the desirable features of a prolonged residence time at the site of drug absorption owing to increased contact with the absorbing mucosa, resulting in a steep concentration gradient to favor drug absorption, and localization in specified regions to improve and enhance the bioavailability of the drug. 7 Factors such as cross-linking status, ionic modification, and salt formation can significantly influence the ability of a material to show substantial mucoadhesion in an in vitro system.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods

2004

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The mucoadhesive properties of chitosan microspheres prepared by different methods were evaluated by studying the interaction between mucin and microspheres in aqueous solution. The interaction was determined by the measurement of mucin adsorbed on the microspheres. A strong interaction between chitosan microspheres and mucin was detected. The intensity of the interaction was dependent upon the method of preparation of chitosan microspheres and the amount of mucin added. The extent of mucus adsorption was proportional to the absolute values of the positive zeta potential of chitosan microspheres. The zeta potential in turn was found to be dependent upon the method of preparation of microspheres. The adsorption of type III mucin (1% sialic acid content) was interpreted using Freundlich or Langmuir adsorption isotherms. The values of r 2 were greater for Langmuir isotherm as compared with Freundlich isotherm. The adsorption of a suspension of chitosan microspheres in the rat small intestine indicated that chitosan microspheres prepared by tripolyphosphate cross-linking and emulsification ionotropic gelation can be used as an excellent mucoadhesive delivery system. The microspheres prepared by glutaraldehyde and thermal cross-linking showed good stability in HCl as compared with microspheres prepared by tripolyphosphate and emulsification ionotropic gelation.

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Section: Introductionmentioning

confidence: 99%

Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods

2004

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“…Biodegradable microspheres have been extensively investigated as delivery systems for biologically active peptides and proteins (Schrier & DeLuca, 1999;Woo et al, 2001). Sustained-release characteristics of microspheres reduce the need for frequent administrations and enhance patient compliance by maintaining in vivo drug levels in the therapeutic range (Okada et al, 1991).…”

Section: Microspheres and Microparticles As Protein Stabilizermentioning

confidence: 99%

Carrier mediated protein and peptide stabilization

et al. 2010

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“…PLGA microsphere delivery systems for rhBMP-2 have been previously reported [16,[24][25][26]. In a study of various carriers for rhBMP-2 microspheres, Rodgers et al [26] found that methylcellulose elicited more fibrosis than did carboxymethylcellulose (CMC) and that CMC alone (ie, with no added rhBMP-2 microspheres) showed a mild promotion of bone growth.…”

Section: Introductionmentioning

confidence: 99%

Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing

et al. 2001

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The hypothesis of this research was that implants of poly(lactide-co-glycolide) (PLGA) microspheres loaded with bone morphogenetic protein-2 (rhBMP-2) and distributed in a freeze-dried carboxymethylcellulose (CMC) m atrix would produce more new bone than would matrix implants of non-protein-loaded microspheres or matrix implants of only CMC. To test this hypothesis it was necessary to fashion microsphereloaded CMC implants that were simple to insert, fit precisely into a defect, and would not elicit swelling. Microspheres were produced via a water-in-oil-in-water double-emulsion system and were loaded with rhBMP-2 by soaking them in a buffered solution of the protein at a concentration of 5.4 mg protein per gram of PLGA. Following recovery of the loaded microspheres by lyophilization, matrices for implantation were prepared by lyophilizing a suspension of the microspheres in 2% CMC in flat-bottom tissue culture plates. Similar matrices were made with 2% CMC and with 2% CMC containing blank microspheres. A full-thickness calvarial defect model in New Zealand white rabbits was used to assess bone growth. Implants fit the defect well, allowing for direct application. Six weeks postsurgery, defects were collected and processed for undecalcified histology. In vitro, 60% of the loaded rhBMP-2 released from devices or microspheres in 5 to 7 days, with the unembedded microspheres releasing faster than those embedded in CMC. In vivo, the rhBMP-2 microspheres greatly enhanced bone healing, whereas nonloaded PLGA microspheres in the CMC implants had little effect. The results showed that a lyophilized device of rhBMP-2/PLGA microspheres in CMC was an effective implantable protein-delivery system for use in bone repair.

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Recombinant Human Bone Morphogenetic Protein-2 Binding and Incorporation in PLGA Microsphere Delivery Systems

Cited by 64 publications

References 23 publications

Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods

Evaluation of mucoadhesive properties of chitosan microspheres prepared by different methods

Carrier mediated protein and peptide stabilization

Effect of a freeze-dried CMC/PLGA microsphere matrix of rhBMP-2 on bone healing

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