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Characteristics of rhVEGF Release from Topical Hydrogel Formulations

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Abstract

Purpose

To study recombinant human vascular endothelial growth factor (rhVEGF), the release characteristics from topical gel formulations, and its interaction with the gelling agents.

Methods

The release kinetics were followed by quantifying rhVEGF that diffused into the receptor chamber of Franz cells. Analytical ultracentrifuge (AUC) was used to characterize the sedimentation velocity of rhVEGF experienced in the gel. The interactions were characterized by isothermal calorimetry (ITC), and rhVEGF conformation was assessed by circular dichroism (CD).

Results

The fraction of protein released was linear with the square root of time. The release rate constants did not show significant change within a wide range of bulk viscosities created by different concentrations of hydroxypropyl methylcellulose (HPMC) or MC gels. Sedimentation velocity determined by AUC generated comparable sedimentation coefficients of protein in these gels. AUC and ITC revealed no significant interaction between rhVEGF and HPMC and some change on secondary structure of the protein by Far UV CD, which was not the case with carboxymethyl cellulose (CMC).

Conclusions

Microviscosity, not bulk viscosity, was the key factor for the release of rhVEGF from cellulosic gels such as HPMC. Interaction between rhVEGF and CMC resulted in slower, and reduced amount of, release from the gel.

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Abbreviations

AUC:

analytical ultracentrifugation

CD:

circular dichroism

CMC:

sodium carboxymethylcellulose

FGF:

fibroblast growth factor

HPMC:

hydroxypropylmethylcellulose

ITC:

isothermal titration calorimetry

MC:

methylcellulose

PDGF:

platelet derived growth factor

rhVEGF:

recombinant human vascular endothelial growth factor

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Acknowledgments

The authors thank Dr. Sherry Martin-Moe for supporting this study, Ms. Linda Khym for editing the manuscript, Dr. Tom Patapoff for helpful discussions, and Dr. Ann Daugherty and Ms. Erika Ingham for collaborating on the development of the gel formulations.

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Authors and Affiliations

  1. Late Stage Pharmaceutical and Processing Development, 1 DNA Way, South San Francisco, California, 94080, USA

    Junyan A. Ji, Jun Liu, Steven J. Shire, Tim J. Kamerzell, Sung Hong & Y. John Wang

  2. Early Stage Pharmaceutical Development, 1 DNA Way, South San Francisco, California, 94080, USA

    Ye Shen

  3. Assay Technology Department, Genentech, 1 DNA Way, South San Francisco, California, 94080, USA

    Karen Billeci

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  1. Junyan A. Ji
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Correspondence to Junyan A. Ji.

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Ji, J.A., Liu, J., Shire, S.J. et al. Characteristics of rhVEGF Release from Topical Hydrogel Formulations. Pharm Res 27, 644–654 (2010). https://doi.org/10.1007/s11095-009-0039-4

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  • DOI: https://doi.org/10.1007/s11095-009-0039-4

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