Salt effect on solubilization of hydrophobic drugs in block copolymeric micelles and investigation of their in vitro and in vivo oral efficiency

- Salt induced micellization and gelation of an EO-PO star block copolymer, Tetronics® 1107 is reported.
- Lipophilic drugs viz. curcumin and quercetin showed marked solubility in micelles.
- Results of drug release, in vitro cytotoxicity, trans-membrane permeability and pharmacokinetics are discussed.
- The encapsulated drugs are viable alternative to free drugs.

Here, we explored the phase and micellar behavior of a hydrophilic ethylene oxide-propylene oxide (EO-PO) branched octablock copolymer Tetronic®1107 (T1107; mol.wt.: 15000 g.mol−1, %PEO = 70, and HLB 18-23) in water and in aqueous NaCl solutions by dynamic light scattering (DLS) and small angle neutron scattering (SANS). Solubilization of two poorly water soluble antioxidant and anticancer drugs viz. curcumin and quercetin in the micelles was investigated by UV-spectrophotometry. The copolymer self-assembles to form nanosize micelles in dilute solution. The results also demonstrated that micelles markedly enhanced apparent solubility of the drugs and in vitro release profiles. Different kinetic models demonstrated drug release from micelles by the diffusion process. Cytotoxic effect of the drugs against Caco-2 cell line, permeability across Caco-2 cell monolayer, pharmacokinetic parameters and tissue distribution in Wistar rats performed for free and solubilized drugs, demonstrated marked effects of micelles on cytotoxicity, permeability and pharmacokinetics.

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