Cellular uptake and anticancer effects of mucoadhesive curcumin-containing chitosan nanoparticles.
Curcumin, which is derived from turmeric has gained much attention in recent years for its anticancer activities against various cancers. However, due to its poor absorption, rapid metabolism and elimination, curcumin has a very low oral bioavailability. Therefore, we have formulated mucoadhesive nanoparticles to deliver curcumin to the colon, such that prolonged contact between the nanoparticles and the colon leads to a sustained level of curcumin in the colon, improving the anticancer effect of curcumin on colorectal cancer. The current work entails the ex vivo mucoadhesion study of the formulated nanoparticles and the in vitro effect of mucoadhesive interaction between the nanoparticles and colorectal cancer cells. The ex vivo study showed that curcumin-containing chitosan nanoparticles (CUR-CS-NP) have improved mucoadhesion compared to unloaded chitosan nanoparticles (CS-NP), suggesting that curcumin partly contributes to the mucoadhesion process. This may lead to an enhanced anticancer effect of curcumin when formulated in CUR-CS-NP. Our results show that CUR-CS-NP are taken up to a greater extent by colorectal cancer cells, compared to free curcumin. The prolonged contact offered by the mucoadhesion of CUR-CS-NP onto the cells resulted in a greater reduction in percentage cell viability as well as a lower IC50, indicating a potential improved treatment outcome. The formulation and free curcumin appeared to induce cell apoptosis in colorectal cancer cells, by arresting the cell cycle at G2/M phase. The superior anticancer effects exerted by CUR-CS-NP indicated that this could be a potential treatment for colorectal cancer.
Discipline of Pharmacy, Monash University Malaysia, Selangor, Malaysia. Electronic address: alice.chuah@monash.edu.
Lay Hong
LH
Chuah
School of Pharmacy, The University of Nottingham, Nottingham, United Kingdom.
Clive J
CJ
Roberts
School of Pharmacy, The University of Nottingham Malaysia Campus, Selangor, Malaysia.
Nashiru
N
Billa
Genetic & Regenerative Medicine Research Centre, Medical Genetics Laboratory, Faculty of Medicines and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Syahril
S
Abdullah
Genetic & Regenerative Medicine Research Centre, Medical Genetics Laboratory, Faculty of Medicines and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia; UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Rozita
R
Rosli
D000268:Adhesiveness / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003474:Curcumin / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D048271:Chitosan; D003474:Curcumin
Cellular uptake; Colorectal cancer; Curcumin; Mucoadhesion; Nanoparticles