There is interest in developing a vaccine to prevent heterosexual transmission of HIV. Currently research focuses on delivering candidate vaccine in simple aqueous gels vaginally. In this thesis a range of polymeric gels were developed and formulated into freeze-dried tablets (FDTs) to improve both retention and stability of gel formulations. The characterisation techniques used included differential scanning calorimetry, thermogravimetric analysis, rheological and textural profile analysis, drug release and efficacy in animal models. A universal placebo gel was manufactured for the vaginal administration of a candidate HIV vaccine to animals. The results showed induction of HIV specific antibodies, but the effect was not sustained. Then, single polymeric FOTs made from Noveon, hydroxypropylmethylcellulose and hydroxyethylcellulose (HEC) were formulated to obtain sustained drug release. Noveon FDTs showed the most sustained drug release. A second animal study was conducted using another candidate HIV vaccine in gelatin and mannitol FOTs designed to achieve immediate and intermediate drug release via the sublingual route. The results showed inability of the antigen to induce protective antibodies against the HIV-l virus. Next a range of FOTs using combinations of three polymers including each of the mucoadhesive polymers (Noveon, chitosan, sodium carboxymethylcellulose-NaCMC), plus HEC and polyvinylpyrrolidone-PVP were developed to improve sustained drug delivery. Results revealed that the RSV formulations showed more sustained drug release profile than the universal placebo gel. The rheological and textural properties of the formulations were determined. Noveon and chitosan formulations were selected as best formulation for vaginal drug delivery. A pilot stability study of these two formulations revealed BSA instability over the 9-week study period. Although a stable vaccine was not achieved, this work shows the potential for gel-based FD tablets to become widely used in the sustained delivery of HI V microbicides and vaccines vaginally in place of aqueous gels.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:579566 |
| Date | January 2012 |
| Creators | Anekwe, Uche |
| Publisher | Queen's University Belfast |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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