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Poor aqueous solubility of anticancer drug bortezomib (BTZ) still remain a major challenge in the successful formulation development. The dendrimeric platform can provide an opportunity to deliver BTZ with improved… Click to show full abstract
Poor aqueous solubility of anticancer drug bortezomib (BTZ) still remain a major challenge in the successful formulation development. The dendrimeric platform can provide an opportunity to deliver BTZ with improved solubility. BTZ encapsulated in PEGylated PAMAM dendrimers (BTZ-PEG-PAMAM) was characterized and evaluated comparatively with encapsulated and conjugated dendritic formulations. The particle size of BTZ-PEG-PAMAM was 188.6 ± 4.17 nm, with entrapment efficiency of 78.61 ± 2.91% and drug loading of 39.30 ± 1.98%. The aqueous solubility of BTZ in PAMAM-PEG conjugate was enhanced by 68.11 folds in comparison to pure drug. In vitro drug release profile was found to be sustained up to 72 hours. A comparative colorimetric MTT assay against A549 and MCF-7 cancer cells resulted in maximum efficacy from BTZ-PEG-PAMAM with IC50 value 333.14 ± 15.42 and 152.60 ± 24.56 nM, respectively. Significantly higher cellular internalization was observed in FITC tagged BTZ-PEG-PAMAM. In vivo pharmacokinetic study performed on Sprague Dawley rats resulted in 8.63 folds increase in bioavailability for BTZ-PEG-PAMAM than pure drug. Pharmacokinetic parameters of BTZ-PEG-PAMAM were better and improved over pure BTZ and other dendritic formulations. The results concluded that the prepared formulation of BTZ-PEG-PAMAM has given significant results and can be studied further for BTZ delivery in the future.