Abstract
Dendrimers are proven solubilizers of hydrophobic as well as hydrophilic drugs in its internal architecture. However, the toxicity of cationic dendrimers restricts its future possibilities as successful formulation. Hybrid systems such as lipid-dendrimer have shown great potential as drug delivery system due to their multifunctional adjustability, and biocompatibility. In the present study, liposomal dendrimer based nano-hybrid (called dendrosomes) of BTZ (bortezomib) were prepared and characterized through time-dependent transmission electron microscope (TEM) as well as photon correlation spectroscopy. Two types of prepared dendrosomes (DS1 and DS2) exhibited size of 145 ± 2.69 and 147 ± 3.26 nm, respectively. The overall hemolytic toxicity of the developed DS1 and DS2 dendrosomes was 4.96 ± 0.45 and 3.19 ± 0.32% (p < 0.005) respectively, which was lower than the dendrimeric formulation of BTZ encapsulated dendrimer (PD) at 50 ppm. Developed dendrosomes showed about 66.65 ± 1.5, and 69.03 ± 1.7% release of BTZ at pH 5.4 (72 h) from DS1 and DS2, respectively. Faster release of BTZ in case of acidic pH was in favour of the anti-tumor effectivity. The IC50 (minimum inhibitory concentration) values (216.9 ± 12.35 and 299.6 ± 21.61 nM) of DS1 and DS2, respectively against A549 cells were significantly lower in comparison to BTZ alone (p < 0.0001). BTZ loaded dendrosomes (DS1) exhibited higher cellular uptake in A549 cells, as evidenced by FITC (fluorescein isothiocyanate) tagged DS1 and DS2 cell uptake images. Overall, BTZ was attempted to be delivered through developed dendrosomes and evaluated. The effectiveness of BTZ was significantly improved against A549 cells compared to other nanoformulations.
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Abbreviations
- BTZ:
-
Bortezomib
- PAMAM:
-
Polyamidoamine
- PD:
-
BTZ loaded PAMAM dendrimers
- CH:
-
Cholesterol
- SUV:
-
Small unilamellar vesicle
- LD:
-
BTZ loaded liposomes
- DS1:
-
BTZ loaded dendrimers and liposomal hybrids
- DS2:
-
BTZ loaded dendrimers and BTZ loaded liposomal hybrids
- HPLC:
-
High-performance liquid chromatography
- MTT:
-
3-(4, 5-dimethyl thiazolyl-2)-2,5-diphenyltetrazolium bromide
- FITC:
-
Fluorescein isothiocyanate
- DMEM:
-
Dulbecco’s modified eagle's medium
- FBS:
-
Fetal bovine serum
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Acknowledgements
The authors would like to acknowledge the financial support received from Department of Science and Technology and University Grants Commission, New Delhi, India to Dr. Umesh Gupta in the form of DST Start up Research Grant (for Young Scientists) and UGC-Start up grant.
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Kumar, V., Khan, I. & Gupta, U. Lipid-dendrimer nanohybrid system or dendrosomes: evidences of enhanced encapsulation, solubilization, cellular uptake and cytotoxicity of bortezomib. Appl Nanosci 10, 4049–4062 (2020). https://doi.org/10.1007/s13204-020-01515-7
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DOI: https://doi.org/10.1007/s13204-020-01515-7