Nanoparticle Delivery of Delamanid for Cost-effective Treatment of Tuberculosis, Satya K Nayagam, UG '22 (2310833)
Tuberculosis remains a major health issue in the world today with over 10 million cases a year. Delamanid (Deltyba) is a new drug for the treatment of multidrug-resistant TB that was approved in 2014. Deltyba exhibits a poor solubility in water and thus is not easily absorbed into the body when taken orally. Current formulations of Deltyba are prohibitively expensive, necessitating the need for a new method of delivery. The Prud'homme group has developed a stable nanoparticle formulation for the oral delivery of delamanid using hydroxypropyl methylcellulose acetate succinate (HPMC-AS) polymer in sequential Flash Nanoprecipitation (sFNP). This technique mixes delamanid (in organic solvent) with water in an initial confined impinging jet (CIJ) mixer to form delamanid aggregates, followed quickly by a coating step with HPMC-AS polymer in another CIJ mixer. Nanoparticles with core loadings (amount of drug compared to polymeric stabilizer) over 90% have been made, thus adding relatively little polymer cost to the total cost of treatment. Initial in-vitro dissolution tests in simulated gastric fluids for the fasted and fed state show fast, high (~100% in fed, ~60% in fasted) release of delamanid from the nanoparticles into solution. This suggests that bioavailability of delamanid delivered in this nanoparticle form will be high, increasing the efficiency of delivery by reducing the amount of drug that is not taken up by the body in a given dose (decreasing dose size). Next steps include the scaling up of nanoparticle production, testing aged nanoparticles for stability over time, and eventual animal studies.