Özet:

In present research, we presented a new approach for formulating nanosized, Ibrutinib bubbles by incorporation into chitosan shelled nanobubbles. The effect of L-α- Phosphatidylcholine (A), concentration of chitosan (B) and concentration of palmitic acid (C), on the particle size and polydispersity index of nanobubbles as studied by 33 Box-Behnken design. About 17 experiments were randomly arranged by Design Expert® software and statistically analyzed by multiple regression analysis .the optimized formulation obtained using numerical optimization technique by setting restrictions on the response parameters. The three optimized (B1-B3) formulations were evaluated. The results reveal that the superficial morphology and core-shell structure of nanobubbles was in the size range of 150-200 nm. The nanobubble formulations were able to load ibrutinib with an encapsulation efficiency of 82.58 % and loading capacity of 17%. In vitro release profile of ibrutinib from nanobubbles show that amount of drug released from nanobubbles was significantly higher(93.52%) than that from the ibrutinib suspension within 24h. according to fluorescent intensity data generated from HepG2 cells, mean fluorescence intensity of 6.12 in HepG2 cells, which is 1.5 times higher than that treated with Ibrutinib Nanobubbles without ultrasound. The In-vitro cytotoxicity study indicated that ultrasound assisted nanobubbles can effectively release in the cells with high sensitivity. The results have shown that the nanobubbles were better apposite for contrast enhanced tumor imaging and subsequent therapeutic delivery.

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