Characterisation of protein stability in rod-insert vaginal rings

Aditya Pattani, Deborah Lowry, Rhonda M Curran, Stephanie McGrath, Vicky L Kett, Gavin P Andrews, R Karl Malcolm

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    A major goal in vaccine development is elimination of the ‘cold chain’, the transport and storage system for maintenance and distribution of the vaccine product. This is particularly pertinent to liquid formulation of vaccines. We have previously described the rod-insert vaginal ring (RiR) device, comprising an elastomeric body into which are inserted lyophilised, rod-shaped, solid drug dosage forms, and having potential for sustained mucosal delivery of biomacromolecules, such as HIV envelope protein-based vaccine candidates. Given the solid, lyophilised nature of these insert dosage forms, we hypothesised that antigen stability may be significantly increased compared with more conventional solubilised vaginal gel format. In this study, we prepared and tested vaginal ring devices fitted with lyophilised rod inserts containing the model antigen bovine serum albumin (BSA). Both the RiRs and the gels that were freeze-dried to prepare the inserts were evaluated for BSA stability using PAGE, turbidimetry, microbial load, MALDITOF and qualitative precipitate solubility measurements. When stored at 4 ◦C, but not when stored at 40 ◦C/75% RH, the RiR formulation offered protection against structural and conformational changes to BSA. The insert also retained matrix integrity and release characteristics. The results demonstrate that lypophilised gels can provide relative protection against degradation at lower temperatures compared to semi-solid gels. The major mechanism of degradation at 40 ◦C/75% RH was shown to be protein aggregation. Finally, in a preliminary study, we found that addition of trehalose to the formulation significantly reduces the rate of BSA degradation compared to the original formulation when stored at 40 ◦C/75% RH. Establishing the mechanism of degradation, and finding that degradation is decelerated in the presence of trehalose, will help inform further development of RiRs specifically and polymer based freeze-dried systems in general.
    LanguageEnglish
    Pages89-97
    JournalInternational Journal of Pharmaceutics
    Volume430
    DOIs
    Publication statusPublished - 2 Apr 2012

    Fingerprint

    Female Contraceptive Devices
    Protein Stability
    Bovine Serum Albumin
    Vaccines
    Trehalose
    Gels
    Dosage Forms
    Foams and Jellies Vaginal Creams
    Nephelometry and Turbidimetry
    Human Immunodeficiency Virus Proteins
    Antigens
    Equipment and Supplies
    Refrigeration
    Solubility
    Polymers
    Maintenance
    Temperature
    Pharmaceutical Preparations
    Proteins

    Cite this

    Pattani, A., Lowry, D., Curran, R. M., McGrath, S., Kett, V. L., Andrews, G. P., & Malcolm, R. K. (2012). Characterisation of protein stability in rod-insert vaginal rings. International Journal of Pharmaceutics, 430, 89-97. https://doi.org/10.1016/j.ijpharm.2012.03.036
    Pattani, Aditya ; Lowry, Deborah ; Curran, Rhonda M ; McGrath, Stephanie ; Kett, Vicky L ; Andrews, Gavin P ; Malcolm, R Karl. / Characterisation of protein stability in rod-insert vaginal rings. In: International Journal of Pharmaceutics. 2012 ; Vol. 430. pp. 89-97.
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    Pattani, A, Lowry, D, Curran, RM, McGrath, S, Kett, VL, Andrews, GP & Malcolm, RK 2012, 'Characterisation of protein stability in rod-insert vaginal rings', International Journal of Pharmaceutics, vol. 430, pp. 89-97. https://doi.org/10.1016/j.ijpharm.2012.03.036

    Characterisation of protein stability in rod-insert vaginal rings. / Pattani, Aditya; Lowry, Deborah; Curran, Rhonda M; McGrath, Stephanie; Kett, Vicky L; Andrews, Gavin P; Malcolm, R Karl.

    In: International Journal of Pharmaceutics, Vol. 430, 02.04.2012, p. 89-97.

    Research output: Contribution to journalArticle

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    AU - Andrews, Gavin P

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