Fabrication of Cyclodextrin Nanosponges for Bortezomib Delivery with In-vitro and In-vivo Characterization

Abstract

Purpose: Fabrication of cyclodextrin nanosponges for bortezomib delivery with in-vitro and in-vivo characterization. Background: Bortezomib (BTZ) as an anticancer drug has been used through the injection pathway. This drug also acts as a p-glycoprotein substrate with almost low dissolution rate. Research design and methods: Two types of Cyclodextrin nanosponges (CDNSs) with different cross-linker ratio were synthetized and their size properties were analyzed by DLS and TEM instruments. FTIR and DSC analysis were done to characterize and compare the interactions through encapsulation. Drug content was determined quantitatively in each requisite section by validated HPLC method. Both carriers were analyzed for loading efficiencies and in-vitro release. Cell studies and intestinal permeability of selected CDNS were determined using MTT and SPIP method, respectively. Results: Both types of CDNSs, encapsulated BTZ in their nano-porous structure, but better loading was shown in CDNS 1:4 (EE: 72%) in comparison with CDNS 1:2 (EE: 51.5%). FTIR and DSC results proved considerable encapsulation of BTZ into CDNSs. The slow and prolonged release profile was observed for CDNS 1:4 in comparison with CDNS 1:2. An increased dissolution rate was also shown in both of loaded nanosystems in comparison with plain BTZ. Based on in-vitro results, BTZ- CDNS 1:4 was chosen as a selected nanosystem for further analysis. This non-toxic carrier revealed considerable uptake (93.9% in 3h) against the MCF-7 cell line but indicated higher IC50 in comparison with the plain drug. This carrier also could improve the rat intestinal permeability of BTZ almost 5.8 times. Conclusion: CDNS 1:4 has the ability to be introduced as a non-toxic carrier for BTZ delivery with its high loading, controlled release manner, high cellular uptake, and permeability improvement characteristics.