Curcumin-cyclodextrin encapsulated chitosan nanoconjugates with enhanced solubility and cell cytotoxicity.
Curcumin (CUR), a naturally derived anti-cancer cocktail is arguably the most widely studied neutraceutical. Despite a lot of promises, it is yet to reach the market as an active anti-cancer formulation. In the present study, we have prepared highly soluble (3 mg/ml) CUR-γ-hydroxypropyl cyclodextrin (CUR-CD) hollow spheres. CUR-CD hollow spheres were prepared by a novel and scalable spray drying method. CUR-CD was then encapsulated into positively charged biodegradable chitosan (CUR-CD-CS) nanoparticles. The CUR-CD-CS nanoparticles were characterised by TEM, SEM, DLS, drug loading and in vitro release. We tested the efficacy of these CUR-CD-CS nanoparticles in SCC25 cell lines using MTT assay and investigated its cellular uptake mechanism. We also studied Oligo DNA loading in CUR-CD-CS nanoparticles and its delivery via confocal imaging and FACS analysis. Our results demonstrated that CUR-CD-CS nanoparticles showed superior in vitro release performance and higher cytotoxicity in SCC25 cell line amongst all tested formulations. The cytotoxicity results were corroborated by cell cycle analysis and apoptosis test, showing nearly 100% apoptotic cell death in the case of CUR-CD-CS nanoparticles. Compared to CS nanoparticles, CS-CD nanoformulation showed higher cellular delivery of Cy3-Oligo DNA which was tested quantitatively using flowcytometry analysis, indicating that CD not only enhanced CUR solubility but also boosted the cellular uptake. Our study shows that rationally designed bio-degradable natural biomaterials have great potential as next generation nano-carriers for hydrophobic drug delivery such as CUR with potential of dual drug-gene delivery.
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia; The School of Pharmacy, The University of Queensland, Brisbane, QLD 4072, Australia; Mucosal Diseases Group, Mater Research Institute - The University of Queensland, Translational Research Institute, 37 Kent Street, Woolloongabba, QLD 4102, Australia.
Amirali
A
Popat
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
Surajit
S
Karmakar
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
Siddharth
S
Jambhrunkar
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia.
Chun
C
Xu
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD 4072, Australia. Electronic address: c.yu@uq.edu.au.
Chengzhong
C
Yu
D002152:Calorimetry, Differential Scanning; D002232:Carbocyanines / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008027:Light; D058726:Nanoconjugates / Q000737:chemistry* / Q000648:ultrastructure; D012542:Scattering, Radiation; D012995:Solubility; D047408:gamma-Cyclodextrins / Q000737:chemistry*
D002232:Carbocyanines; D058726:Nanoconjugates; C089187:cyanine dye 3; D047408:gamma-Cyclodextrins; C479659:hydroxypropyl-gamma-cyclodextrin; D048271:Chitosan; D003474:Curcumin
Cellular delivery; Chitosan; Curcumin; Cyclodextrin; Spray drying