Dual drug loaded chitosan nanoparticles-sugar--coated arsenal against pancreatic cancer.
Pancreatic cancer is an aggressive form of cancer with poor survival rates. The increased mortality due to pancreatic cancer arises due to many factors such as development of multidrug resistance, presence of cancer stem cells, development of a stromal barrier and a hypoxic environment due to hypo-perfusion. The present study aims to develop a nanocarrier for a combination of drugs that can address these multiple issues. Quercetin and 5-fluorouracil were loaded in chitosan nanoparticles, individually as well as in combination. The nanoparticles were characterized for morphology, size, zeta potential, percentage encapsulation of drugs as well as their release profiles in different media. The dual drug-loaded carrier exhibited good entrapment efficiency (quercetin 95% and 5-fluorouracil 75%) with chitosan: quercetin: 5-fluorouracil in the ratio 3:1:2. The release profiles suggest that 5-fluorouracil preferentially localized in the periphery while quercetin was located towards the core of chitosan nanoparticles. Both drugs exhibited considerable association with the chitosan matrix. The dual drug-loaded carrier system exhibited significant toxicity towards pancreatic cancer cells both in the 2D as well as in the 3D cultures. We believe that the results from these studies can open up interesting options in the treatment of pancreatic cancer.
Centre for Nanotechnology & Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India.
Karolyn Infanta
KI
David
Centre for Nanotechnology & Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India.
Leela Raghav
LR
Jaidev
Centre for Nanotechnology & Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India.
Swaminathan
S
Sethuraman
Centre for Nanotechnology & Advanced Biomaterials, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, India. Electronic address: umakrishnan@sastra.edu.
Uma Maheswari
UM
Krishnan
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002460:Cell Line; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011794:Quercetin / Q000008:administration & dosage* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004337:Drug Carriers; D048271:Chitosan; D011794:Quercetin; D005472:Fluorouracil
3-D model; 5-Fluorouracil; Chitosan; Dual drug-loaded carrier; Pancreatic cancer; Quercetin