Background: Pazopanib is second-generation tyrosinekinase inhibitor used in Colorectal
cancer (CRC) which is effective orally. Targeted liposomal drug delivery will reduce the
unwanted side effects of the drug. The application of High-pressure homogenizers for the
preparation of systems like liposomes and lipid dispersions is rising because of its ability
of vesicle disruption. Aim: Major objective of present research work was to optimize
high pressure homogenization process for formulation of colon targeted liposomal
drug delivery system of Pazopanib and its
in-vivo evaluation. To study the influence of
homogenization Pressure and number of cycles on some parameters, such as vesicle size
and polydispersity index (PDI). Materials and Methods: The liposomes were formulated
with HSPC (Hydrogenated Phosphotidylcholin from Soybean) m-PEG DSPE-2000
(Phospolipid) and Cholesterol using Ethanol injection method followed by downsizing
by EmilsiFlex High pressure Homogenizer. Results and Conclusion: The liposomes were
evaluated for entrapment efficiency,
in-vitro drug release, osmolality, particle size, size
distribution, polydispersity index, FEG-SEM and stability studies. Optimization studies
concluded that the optimized formulation with homogenization pressure of 1000, 1500,
2000 psi and number of cycle 9, 6, 6 respectivly gives particle size of 109 nm with PDI
0.998 and desirability 0.975.
In-vivo studies in wrister rats in which carcino genesis was
done using 1,2- dimethylhydrazine (DMH), indicated that Pazopanib liposomes caused
significant tumors growth suppression in terms of tumor volume and weight as compared
to control. Histo-pathological evaluation showed that the animals treated with pazopanib
liposomes had moderate dysplasia where as untreated animals had severe dysplasia.