Title : Design and formulation of doxycycline polymeric nanoparticles and testing antitumor and antiangiogenic activity in mouse colon cancer model
Nanotherapeutics is a rapidly progressing area in the field of Nanomedicine, which is being utilized to overcome several limitations of conventional drug, including poor aqueous solubility, lack of site-specific targeting, rapid systemic clearance, intestinal metabolism and systemic toxicities. Polymeric nanoparticles (PNPs) consist of the drug dispersed in an amorphous form within a polymer matrix. PNPs are promising vehicles for drug delivery by easy manipulation to prepare carriers with the objective of delivering the drugs to specific targets; such an advantage improves the drug safety. The main objective of our study is to formulate pH-sensitive polymeric nanoparticles loaded with Doxycycline using Nanoprecipitation technique using Eudragit S100 (ES100) and Hydroxypropyl methyl cellulose phthalate HP55 (HPMCP HP55) as polymers. Sixty male albino mice were divided into 6 experimental groups. Experimental colon cancer was induced by chemical injection of 1,2,-dimethylhydrazine once weekly for 16 weeks. Doxycycline polymeric nanoparticles (DOX-PNPs) were administered orally in 5 and 10 mg/kg doses and compared to free doxycycline. The results of the biological study demonstrated greater antitumor activity for DOX-PNPs as demonstrated by the improved histopathological picture for colon specimens stained with hematoxylin and eosin and lessening of the tumor score. Further, the DOX- PNPs significantly lowered the angiogenesis markers, VEGD and CD31, compared to free DOX. Overall, the current results highlighted greater antitumor action for DOX-PNPs and their promise for use in clinical trials to show their efficacy in treating human colon cancer.