Development and evaluation of mucoadhesive bigel containing tenofovir and maraviroc for HIV prophylaxis.

BACKGROUND: Sexual transmission of HIV is the most common means of acquiring the disease. Topical microbicides have been investigated to prevent transmission. This study will use a specific entry inhibitor, maraviroc, and a nucleotide reverse transcriptase inhibitor (NRTI), tenofovir, a dual combination which will provide a synergist effect that can enhance the efficacy of HIV microbicides via a mucoadhesive dual compartment bigel. Bigel formulation via hydrogel organogel linkages were developed and evaluated for their physicochemical characteristics, safety, and anti-HIV efficacy. In vitro diffusion studies were performed with Franz diffusion cells having effective diffusion surface area of 1.76cm2 and receiver chamber volume of 15mL. RESULT: The bigel formulations showed a viscosity ranging from 14179 to 14560 cPs and had a good spreadability and acidic pH in the range of 4.0 ± 0.34 to 5.2 ± 0.18. The bigel formulations showed good anti-HIV activity at a concentration of 0.1 µg/mL. The in vitro release study of maraviroc from the bigel formulations showed a release rate ranging from 2.675 to 3.838 µg/cm2/min½ while the release rate for tenofovir ranged from 3.475 to 3.825 µg/cm2/min½. The bigel formulations were non-toxic to the human vagina as there was < 1 log10 change in Lactobacilli crispatus viability. CONCLUSION: This study successfully developed a dual compartment bigel containing maraviroc and tenofovir. BG C was found to be stable and safe towards vaginal and rectal epithelium, and it actively prevented HIV transmission. This bigel has the potential for long-term pre-exposure prophylaxis prevention of HIV transmission.

Phenotyping and genotyping of CYP2C19 using comparative metabolism of proguanil in sickle-cell disease patients and healthy controls in Nigeria.

Polymorphic expression of metabolic enzymes have been identified as one of the key factors responsible for the interindividual/ethnic/racial variability in drug metabolism and effect. In Nigeria, there is a disproportionately high incidence of sickle-cell disease (SCD), a condition characterized by painful crisis frequently triggered by malaria. Proguanil, a substrate of the polymorphic CYP2C19, is a chemoprophylactic antimalarial drug widely used among SCD patients in Nigeria. This study aimed to conduct a comparative CYP2C19 phenotyping among SCD patients and healthy controls and to compare the results with those previously reported. One hundred seventy-seven unrelated subjects comprising 131 SCD patients and 46 non-SCD volunteers were phenotyped. This was carried out by collecting pooled urine samples over 8 h following PG administration. Proguanil and its major CYP2C19-dependent metabolites were measured by high-performance liquid chromatography. Metabolic ratios (MRs) were computed and employed in classifying subjects into poor or extensive metabolizers. Among SCD group, 130 (99.2%) were extensive metabolizers (EMs) and 1 (0.8%) was poor metabolizer (PM) of PG, while 95.7 and 4.3% non-SCDs were EMs and PMs, respectively. MRs ranged from 0.02 to 8.70 for SCD EMs and from 0.22 to 8.33 for non-SCD EMs . Two non-SCDs with MRs of 18.18 and 25.76 and the SCD with MR of 16.77 regarded as PMs had earlier been genotyped as CYP2C19*2/*2. Poor metabolizers of proguanil in SCD patients are reported for the first time. Regardless of clinical significance, a difference in metabolic disposition of proguanil and CYP2C19 by SCDs and non-SCDs was established.

High Cadmium Levels in Cured Meat Products Marketed in Nigeria - Implications for Public Health.

Heavy metals are known to disrupt important physiological processes in living cells, and have been responsible for various pathological conditions with possible contributions to cancer development. Food contamination have been identified as one of the ways humans are exposed to heavy metals. In developing countries like Nigeria, the regulatory framework for enforcing compliance with globally acceptable exposure to deleterious contaminants is poor. In the current study, thirteen samples of cured meat products of diverse origin marketed in South-west Nigeria were evaluated for lead, cadmium, chromium and nickel contents using the atomic absorption spectroscopy technique. All the samples analysed contained cadmium between 0.35 and 1.20 ppm, levels considered higher than acceptable limits in consumable products. Lead, chromium and nickel were not detected in any of the samples. As known cumulative poisons, there is the need for stringent regulatory control of these heavy metals in cured meat products imported into or produced indigenously in the country in order to minimize the risks to public health.

Formulation of quinine suppository for initiation of early treatment of malaria - a preliminary study.

Background: In the management of malaria, there is the need for early initiation of treatment. An antimalarial drug for home use must be easy to administer, safe, effective and affordable. Parenteral quinine is the gold standard for treatment of severe malaria. A rectal formulation of quinine will therefore serve the purpose of early initiation of care in patients that lack easy access to medical centers. The main objective of this preliminary work was to develop a quinine suppository with adequate release properties that also meets the dual conditions of affordability and ease of administration. Materials and Methods: Cocoa butter and Fattibase™ were used in the preparation of suppositories containing 200 mg quinine bisulphate. The release profiles of formulations with varying concentrations of polysorbate 80 (0 - 5%) were evaluated by in vitro dissolution in pH 8 buffer medium. Results: The addition of polysorbate 80 improved the release of quinine significantly at 2 and 5%. Cocoa butter suppository with 1% polysorbate 80 released 73.6 mg quinine bisulphate in 1 hr while release from suppositories with 2% and 5% surfactant was higher. Fattibase™ suppositories had better release profiles than cocoa butter formulations. The formulation with 5% polysorbate 80 released 170 mg quinine in 1 hr. Formulations with the two bases released quinine in adequate quantities for the management of malaria. Conclusions: The particle size of quinine is an important factor affecting the physical appearance and drug release from the suppository. The Fattibase™ suppositories were more stable but cost five times the price of the cocoa butter formulations. The cocoa butter formulations, however, still released quinine in sufficient quantities for the management of malaria. Cocoa butter formulations will be more affordable in resource-limited malaria-endemic regions of the world.