Background & objectives: Bisphenol A (BPA) is an endocrine disruptor that is widely used in the manufacture of polycarbonate plastics, epoxy resins and dental sealants. It is known to have adverse effects on spermatogenesis in rodents. This study was aimed to evaluate the effects of BPA in adult common marmoset owing to its similarities with human spermatogenesis. Methods: Sixteen marmosets were divided into four groups (n=4 per group) and given oral doses of BPA (2.5, 12.5 and 25 μg/kg BW/day) for 70 days to cover two spermatogenic cycles, and the control group received only vehicle (honey). Testes were processed for histological and transmission electron microscopy studies. Results: Histology of the testis showed sloughing of germ cells into the lumen, increase in interstitial space and vacuolation of Sertoli cell cytoplasm. Ultrastructural analysis of the testis revealed several degenerative effects on the basement membrane, Sertoli cells, Leydig cells and other developing germ cells in the 12.5 and 25 μg/kg BW/day groups as compared to control. Interpretation & conclusions: The observed ultrastructural changes caused by BPA in testicular morphology might be indicative of a perturbed sperm production. Considering the genetic and spermatogenic similarities of common marmoset (Callithrix jacchus) and humans, the study findings are of significance. Further studies are, however, needed to elucidate the mechanism of action.

Introduction: Ursolic acid (UA) and oleanolic acid (OA) are triterpenoids. They are used to treat numerous diseases, including tuberculosis. Combinations of these drugs provide new insight into the management of tuberculosis. The major obstacle is the effective delivery of these drugs to the lungs, which are mainly affected due to M. tuberculosis. A metered-dose inhaler (MDI) was developed to address this issue containing UA and OA, followed by in-vitro and in-vivo evaluation. Methods: In the present study, MDI formulation was prepared by incorporating UA and OA at the dose level of 120 μg/ml in each actuation. In-vitro evaluation of this MDI formulation was performed to ensure its suitability to deliver UA and OA preciously. With prior approval of IAEC, a pharmacokinetic and acute inhalation toxicity study was conducted using MDI on Wistar rats. Results: The pharmacokinetic study showed an increased biological half-life of UA (9.23±0.104 h) and OA (8.93±0.166 h) in combination therapy. In-vivo toxicity study demonstrated no adverse effects on body weight and vital organs in the treatment group compared with the control group. Histopathology examination of these essential organs showed no abnormalities. Mild alternation in the biochemical and hematological parameters was observed. However, these alterations did not affect the overall health of the animals. Conclusion: The present study documents a detailed study for the safety and pharmacokinetics of UA and OA in-vivo for their advanced application in tuberculosis disease.

Ursolic acid (UA) and oleanolic acid (OA) are hydrophobic triterpenoid isomers with demonstrated anti-mycobacterial (Mtb) and immune-regulatory properties, although their poor solubility limits clinical use. We report the development of solid lipid microparticles (SLMs) as delivery vehicles for UA and OA and evaluate their anti-Mtb efficacy in vitro and in vivo, as well as their acute toxicity. SLMs measured 0.7–0.89 µM in size, with complete in vitro release of OA and UA at 40 and 32 h, respectively. The minimum inhibitory concentration (MIC) of SLMs loaded with OA and UA was 40 µg/mL SLMs + 20 µg/mL OA + 20 µg/mL UA for drug-sensitive Mtb and 80 µg/mL SLMs + 40 µg/mL OA + 40 µg/mL UA for multidrug-resistant (MDR) Mtb. These SLMs showed an efficient reduction in Mtb burden in infected alveolar macrophages. In a murine model of late-stage progressive MDR-TB, aerosolized delivery of SLMs containing OA and UA via a metered-dose inhaler significantly reduced pulmonary bacterial loads and extended survival. In vivo, acute toxicity studies revealed no mortality or signs of toxicity. These findings demonstrate that SLMs are an optimal delivery system for terpenoids, providing potent in vitro and in vivo anti-TB activity with an excellent safety profile.