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Home > Archives > Volume 20, No 8 (2022) > Article

DOI: 10.14704/nq.2022.20.8.NQ44768


Ponnaganti Murali, Rakesh Kumar Meel


In present research, we presented a newapproach for formulating nanosized, Ibrutinibbubbles by incorporation into chitosan shelled nanobubbles. 17 experiments were designed by 33 Box-Behnken design and 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 nanobubbleswas studied and statistically analyzed by multiple regression analysis.The optimized formulation obtained using numerical optimization were evaluated for particle size, zetapotential, Polydispersity index, encapsulation efficiency and loading capacity. In-vivo studies were conducted in rats and evaluated for Cmax, Tmax and AUC. The size range of nanobubbles (1-17) revealed 198.12-416.42 nm and PI was 0.16- 0.51.Theoptimized nanobubble formulations exhibitedparticle size of 201.66nm, PI of 0.16, zetapotential of -39.76, encapsulation efficiency of 82.58 % and loading capacity of 17.12%. In vitro release showed thatthe drug released from nanobubbles was significantly higher (93.52%) compared toibrutinibpure drug within 24h.In-vivo studies in rats showed that nanosponges Cmax of 129.64±2.16 ng/ml was significantly higher (p<0.05) than the pure drug's Cmax of 38.15±1.42 ng/ml. Both the nanosponges formulation and the pure drug had Tmax values of 4.00±0.06 h and 1.5±0.02h, respectively. The nanosponges formulation had a greater AUC0-infinity (3148.36±1.29 ng. h/ml) than the pure drug 987.92± 0.49 ng.h/ml. In comparison to the pure drug, the nanosponges formulation had a considerably greater AUC0-t (p<0.05).A significant enhancement in-vitro dissolution profile and bioavailability of the Ibrutinibnanobubbles was observed compared to pure drug.


Ibrutinib, B cell cancer, chitosan shelled nanobubbles,Box-Behnken design(BBD), Pharmacokinetic studies.

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