title: Bleomycin sulphate loaded nanostructured lipid particles augment oral bioavailability, cytotoxicity and apoptosis in cervical cancer cells.
abstract: 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±5.4nm 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.
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali 140307, Punjab, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Saini
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali 140307, Punjab, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Bansal
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Ankush
authors.initials: A
authors.lastname: Chandra
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali 140307, Punjab, India. Electronic address: jitenderpharmacy@gmail.com.
authors.forename: Jitender
authors.initials: J
authors.lastname: Madan
authors.affiliation: Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali 140307, Punjab, India.
authors.forename: Upendra Kumar
authors.initials: UK
authors.lastname: Jain
authors.affiliation: Dr. B.R Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110007, India.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Chandra
authors.affiliation: Oniosome Health Care Private Limited, Mohali 160071, Punjab, India.
authors.forename: Sarvesh Malviya
authors.initials: SM
authors.lastname: Jain
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001682:Biological Availability; D001761:Bleomycin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D018625:Microscopy, Atomic Force; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013997:Time Factors; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology*; D014961:X-Ray Diffraction
chemical_list: D008055:Lipids; D001761:Bleomycin
keywords: Apoptosis; Bioavailability; Bleomycin sulphate; Cellular uptake; Cytotoxicity; Nanostructured lipid particles