Preparation and Evaluation of Oral Capsule-Based Niosomes for the Anti- Cancer Drug Axitinib
DOI:
https://doi.org/10.31351/vol34iss3pp65-77Abstract
Niosomes are bilayer vesicles formed by the self-assembly of non-ionic surfactants, they are receiving increasing attention as a potential oral drug delivery system specifically for poor soluble drugs to enhance its dissolution and ultimately its absorption and oral bioavailability. Axitinib is a tyrosine kinase inhibitor works by blocking the vascular endothelial growth factor receptors (VEGFR), decreasing the development of neovascularization which supress the tumour growth. It is classified as class 11 drug which has low bioavailability due to its poor solubility and absorption. In this study, axitinib (AXT) capsules based niosomes formulated by thin film hydration method as liquid niosomal dispersion using (span 60: cholesterol (1:1 weight ratio), 5mg dicetyl phosphate (DCP) and 5mg drug, with entrapment efficiency 96.5% and particle size 64.5nm), then converted to dry powder via silicified microcrystalline cellulose (SMCC) and evaluated for flow properties, in-vitro drug release, drug-excipients compatibility study, permeation study, cytotoxicity study and bioavailability investigation. The results showed good flow properties of the powder content of prepared capsules based niosomes where the angle of repose was (32.3± 1.1), Carr’s index was (12±0.58) and Hausner ratio was (1.12±0.01). The drug release from capsules based niosomes was rapid in initial phase where 40.61% of drug released from capsules based niosomes in acidic medium (stomach) followed by continuous release (in intestine) where 100% of drug released within 4 hours, while the drug released completely(100% of drug released within 20 minutes ) in acidic medium (stomach) from conventional marketed tablets, the results of FTIR and DSC revealed the purity of drug and incorporation of it in amorphous form and no interaction between drug and excipients. The permeation results revealed that the encapsulation of drug in vesicles enhanced the drug intestinal permeation in comparison to marketed tablets, where the permeation percent of the powder content of capsule based niosmes was 78% while the permeation percent of the marketed tablets was 58%. The study of in-vitro cytotoxicity effect showed that the cytotoxic effect of prepared capsule based niosomes significantly (p<0.05) higher than pure drug and it is increased with time, where the IC50 value for the pure drug and capsule-based niosomes were found to be 120 µg/ml and 80.26 µg/ml respectively. Bioavailability investigation of capsules based niosomes compared with marketed tablets was revealed that capsules based niosomes enhanced the oral bioavailability of axitinib comparison with the marketed tablets, the pharmacokinetic results showed that the capsules base niosomes have been revealed higher peak drug concentration ( Cmax = 5.23±0.07µg/ml) with maximum peak time (Tmax =4hr) while the Cmax= 4.8±0.025µg/ml and Tmax = 6 hr for conventional marketed tablets , AUC 0-∞ for capsule based niosomes was (70.092µg/ml.hr) is highly significant (p<0.05) comparison with AUC 0-∞ for marketed tablets which was( 53.714 µg/ml.hr), this substantial difference suggests an improvement in drug solubility, dissolution, and absorption, eventually leading to an improve in oral bioavailability when drug loaded in nano-carrier (niosomes). The results of this study was indicated that niosomes exhibit potential as nano-carriers for enhancing the cytotoxic effects of anti-cancer drug, permeability and improving their oral bioavailability.
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