Improved oral bioavailability of novel antithrombotic S002-333 via chitosan coated liposomes: a pharmacokinetic assessment

Abstract

S002-333, a novel anti-thrombotic agent, exhibits excellent platelet mediated antithrombotic action and subsequently has no effect on the coagulation cascade. However, its oral bioavailability is hampered due to inherent low aqueous solubility. In order to circumvent this issue, chitosan coated liposomes were prepared by an ethanol injection method. S002-333 loaded liposomes (CH-LIP-F9) were reproduced with homogeneous particle sizes. The liposomal formulation was characterized with respect to size and surface morphology by transmission electron microscopy (TEM). The optimized formulation exhibited spherical shapes with a nano-metric size (249.64 AE 10.36 nm). The percentage entrapment efficiency (% EE) offered by the various developed formulations was found to be in the range between 72.36 AE 1.76 and 76.87 AE 2.32%. An in vitro release experiment demonstrated prolonged release of S002-333 from the optimized liposomal formulation. A cytotoxicity study represented that both blank liposomes (BLK-LIP) as well as the drug bearing liposomal formulation displayed negligible toxicity towards Caco-2 cells.The results of a pharmacokinetic study indicated that liposomal formulation significantly enhanced oral absorption of S002-333 in rats (AUC 0-t ; 7016.02 AE 128.96 h ng mL À1 ) compared to its aqueous suspension (AUC 0-t ; 2382.02 AE 77.17 h ng mL À1 ). These results together elicited that the developed liposomal formulation would improve preclinical and clinical application of S002-333.

Bolalipid-Doped Liposomes: Can Bolalipids Increase the Integrity of Liposomes Exposed to Gastrointestinal Fluids?

“…Liposomes were discovered in 1965 by Bangham and have become the most successful drug delivery system [1,2]. Since it is known that liposomes can increase the absorption of substances from the gastrointestinal tract (GIT)-shown by Sessa et al in 1970 [3]-the idea for using liposomes for oral drug delivery purposes exists, and has been followed for decades by many research groups [4][5][6][7][8]. The encapsulation of drugs in liposomes has many advantages: In addition to the high encapsulation efficiency of lipophilic and hydrophilic drugs, as well as their high biocompatibility, liposomes protect their cargo from external influences such as enzymatic degradation or premature metabolism [9].…”

Evaluation of clinical effectiveness of paclitaxel and ursolic acid co-loaded liposomes as enhanced treatment for head and neck squamous cell carcinoma

“…The inception of novel drug delivery systems has enhanced the anticancer potential of drugs [5,6]. Therefore, in this study, lipid bilayer liposomes (LiP) that can efficiently codeliver both hydrophobic and hydrophilic drugs by co-loading them in their hydrophilic core and hydrophobic lipid vesicles were chosen as for the co-delivery of PTX and UA [5,7,8]. In a recent investigation, it was shown that hybrid nanoconstruct of albumin-PTX hybrid nanoparticle (L-APN) encapsulated in liposome significantly enhanced anticancer effectiveness by increasing the accumulation of PTX in tumor, bio-distribution and pharmacokinetic parameters [9].…”