Bleomycin sulphate loaded nanostructured lipid particles augment oral bioavailability, cytotoxicity and apoptosis in cervical cancer cells

• Nanostructure lipid particles of bleomycin sulphate enhanced the oral bioavailability by averting first pass metabolism.
• Nanostructure lipid particles augmented intestinal lymphatic uptake of bleomycin sulphate to reach the systemic circulation.
• The nanoformulation of bleomycin sulphate improved the cytotoxicity and extent of apoptosis against cervical cancer cells.

In present investigation, bleomycin sulphate loaded nanostructured lipid particles (BLM-NLPs) were constructed to enhance the oral bioavailability by overwhelming the first pass hepatic metabolism. The particles size and nanoencapsulation efficiency of BLM-NLPs were measured to be 17.4 ± 5.4 nm and 45.3 ± 3.4%, respectively. Our studies indicated that the drug was molecularly dispersed in the lipid nanocoacervates, with amorphous geometry, without altering the chemical structure, as ascertained by spectral studies. The nanoformulation, BLM-NLPs was analyzed for dissolution testing, cytotoxicity, apoptosis and cellular uptake in human cervical cancer cell line, HeLa cells. BLM-NLPs released the drug with first order kinetic in simulated intestinal fluid (pH ∼ 6.8 ± 0.1), characterized by initial burst and followed by slow release. Further, an enhanced cytotoxicity (∼5.6 fold lower IC50), improved intracellular concentration (∼4.38 fold) and greater degree of apoptosis was induced by BLM-NLPs in HeLa cells, as compared to BLM alone. Moreover, BLM-NLPs also showed dose-dependent internalization, as evinced by cellular uptake study. The in vivo study indicated a significantly (P < 0.0001) smaller elimination rate constant (KE), volume of distribution (Vd) and clearance rate (CLTotal) for BLM-NLPs, as compared to BLM solution in post-oral administrations. This clearly depicts the retention and stability of tailored nanoformulation in intestinal absorption pathway. In addition, our nanoformulation, BLM-NLPs documented significantly (P < 0.0001) ∼ 3.4 fold (66.20 ± 2.57%) higher bioavailability than BLM solution (19.56 ± 0.79%). In conclusion, our in vitro and in vivo results warrant the safety, efficacy and potency of tailored nanoformulation in clinical settings.

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