Cyclodextrin-based nanocarriers containing a synergic drug combination: A potential formulation for pulmonary administration of antitubercular drugs

International Journal of Pharmaceutics
Giuseppina SalzanoRuxandra Gref

Abstract

Tuberculosis (TB) remains a major global health problem. The use of ethionamide (ETH), a main second line drug, is associated to severe toxic side-effects due to its low therapeutic index. In this challenging context, "booster" molecules have been synthetized to increase the efficacy of ETH. However, the administration of ETH/booster pair is mostly hampered by the low solubility of these drugs and the tendency of ETH to crystallize. Here, ETH and a poorly water-soluble booster, so-called BDM43266, were simultaneously loaded in polymeric β-cyclodextrin nanoparticles (pβCyD NPs) following a "green" protocol. The interaction of ETH and BDM43266 with pβCyD NPs was investigated by complementary techniques. Remarkably, the inclusion of ETH and BDM43266 pβCyD NPs led to an increase of their apparent solubility in water of 10- and 90-fold, respectively. Competition studies of ETH and BDM43266 for the CyD cavities of pβCyD NPs corroborated the fact that the drugs did not compete with each other, confirming the possibility to simultaneously co-incorporate them in NPs. The drug-loaded NP suspensions could be filtered through 0.22μm filters. Finally, the drug-loaded NPs were passed through a Microsprayer® to evaluate the feasibility to adm...Continue Reading

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Citations

Aug 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Arturo SánchezJahir Orozco
May 7, 2020·Advanced Pharmaceutical Bulletin·Dipak Dilip Gadade, Sanjay Sudhakar Pekamwar
Feb 6, 2020·ACS Infectious Diseases·Baptiste VillemagneNicolas Willand
May 2, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kiran PatilGaurav Saraogi

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