Australian and Indian researchers have demonstrated in animal experiments that nanoparticles containing capecitabine can bypass healthy cells and deliver the chemotherapy drug with fewer side effects.
Capecitabine is a first-line treatment for bowel cancer, but the high dosage required can produce toxicities such as bone marrow depression, dermatitis, and hand-foot syndrome. The drug can also be quickly metabolised within six hours.
To help reduce toxicities and create a slower release profile, the researchers loaded the drug on mesoporous silica nanoparticles (MSNs) and coated the MSNs with chitosan, glucuronic acid and Eudragit S-100.
The pH-responsiveness of Chitosan is a good match with the slightly acidic nature of tumour cells as well as being biodegradable and non-toxic. Glucuronic acid is believed to encourage engagement with tumour receptor cells, and Eudragit S-100 was applied to hold the MSNs intact until they reached the colon.
In test tube studies, the capped nanoparticles showed an encouraging release profile over seventy-two hours and better uptake with tumour receptor cells, the researchers reported in the journal Carbohydrate Polymers.
Further studies on 24 rats showed reduced tumour sizes and number compared to those rats receiving straight up capecitabine and those in a control group. Coated MSNs also resulted in better blood parameters, moderate reductions in toxicity in organs, and significantly lower counts of ACF, one of the important markers of colon cancer.
The coated nanoparticles, which took one year to develop, look to be a neat delivery vehicle but there is still some way to go before we see a clinical trial.
“As MSNs have not yet been approved by FDA, clinical translation may be challenging,” said sole Australian researcher on the study, Professor Sanjay Garg of the University of South Australia.
“Further studies need to be performed in rats to obtain the toxicological profile and ascertain the right drug dosage.We hope that in future this could prove to be a vital breakthrough for targeted drug delivery for cancers and chemotherapeutic drugs,” Professor Garg said.