4.2.4 Fluorouracil Nanoparticles:Nanoscaled devices have extraordinarypossibility for drug delivery applications due to their small size.
In the displaystudy, we report for the first time the preparation and assessment of antitumoradequacy of 5-fluorouracil (5-FU)-entrapped poly (D, L-lactic-co-glycolic acid)(PLGA) nanoparticles with reliance on the lactide/glycolide combination ofPLGA. Two different monomer combinations of PLGA nanoparticles loaded with 5-FUwith, 50-50 and 90-10 were produced utilizing a changed double emulsion method,and their biological assessment was done in glioma (U87MG) and breastadenocarcinoma (MCF7) cell lines. 5-FU-loaded PLGA 50-50 nanoparticles exhibitedsmaller size with a high encapsulation efficiency of 66%, which was equivalentto that of PLGA 90-10 nanoparticles. Physicochemical studies of nanoparticles utilizingdifferential scanning calorimetry (DSC) and X-ray diffraction suggested thepresence of 5-FU in molecular dispersion form. In vitro release studies showedthe delayed and sustained release of 5-FU from nanoparticles with both the PLGAcombinations, where PLGA 50-50 nanoparticles showed quicker release.
Nanoparticles with PLGA 50-50 combination preferred cytotoxicity over free drugin a dose- and time-dependent manner against both the tumor cell lines. The improvedefficiency of PLGA 50-50 nanoparticles to actuate apoptosis was indicated byacridine orange/ethidium bromide staining. Cell cycle perturbations examined utilizingflow cytometer demostrated better S-phase arrest by nanoparticles in contrastwith free 5-FU. All the results demonstrate that PLGA 50-50 nanoparticles havebetter antitumor efficacy over PLGA 90-10 nanoparticles and free 5-FU. Since, investigationsdemonstrated that prolonged exposure of diseased tissues to moderate drugconcentrations is more suitable than regular administration of higherconcentration of the drug; our results clearly demonstrated the adequacy of5-FU-entrapped PLGA nanoparticles with reliance on carrier combination as sustainedrelease formulation to multiplex the restorative effect of tumor therapy.i4.2.5 PolyLactic-Co-(Glycolic Acid)-GraftedHyaluronic Acid Copolymer NanoparticlesPLGA-combined HA copolymers were produced and used astargeted micelle carriers for DOX.
Primarily, by nano-complexing withdimethoxy-PEG, HA was disintegrated in an anhydrous DMSO. Then the carboxylicgroups of HA were chemically combined with PLGA to produce HA-g-PLGAcopolymers. This methadology was utilized to produce the hydrophobic PLGAchains over the hydrophilic HA chain. The final resultingHA-g-PLGA self-arranged in aqueous solution to form multi-cored micellaraggregates and DOX was entrapped during the self-assembly.
The advantages ofDOX-loaded HA-g-PLGA micelle nanoparticles that they showed greater cellularabsorption and more potent cytotoxicity over the free DOX against HCT-116 cellsthat over-expressed HA receptor. This demonstrates that they were absorbed bythe cells through HA receptor-mediated endocytosis.ii 4.2.6 Curcumin Nanoparticles:Curcumin is a profoundly potent, nontoxic, bioactive agent found inturmeric and has been known for centuries as a household remedy to manyailments. Low aqueous solubility and poor bioavailability is the onlydisadvantage suffered by this system. The aim of the present study was to designa method for the formation of nanoparticles of curcumin with an aim to improveits aqueous-phase solubility and study the effect on its antimicrobialproperties.
A process based on a wet-milling technique was used to prepare nanoparticlesof curcumin (nanocurcumin) and they were found to have a narrow particle sizedistribution ranging in between 2?40 nm.Dissimilar to curcumin, nanocurcumin was freely dispersible in water in theabsence of any surface active agents. There was no modification in chemicalstructure while nanoparticle preparation and the chemical structure ofnanocurcumin found to be same as that of curcumin. For a variety of bacterialand fungal strains, minimum inhibitory concentration (MIC) of nanocurcumin wasdetermined and was compared to that of curcumin. Studies showed that theaqueous dispersion of nanocurcumin was much more effective than curcuminagainst Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonasaeruginosa, Penicillium notatum, and Aspergillus niger. Particle size reductionup to the nano range can be greatly enhance the water solubility and antimicrobialactivity of curcumin.
The activity of nanocurcumin for the selectedmicroorganisms was more pronounced against Gram-positive bacteria thanGram-negative bacteria. Moreover, its antibacterial activity was potentiallybetter than its antifungal activity. Transmission electron micrograph (TEM)analysis was utilized to study the mechanism of antibacterial action ofcurcumin nanoparticles, which indicated that these particles gain entry to thebacterial cell by totally destroying the cell wall, leading to cell death.iiii Niar K L , Jagadeeshan S , Niar S A , Kumar GS .Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapyand its dependence on the carrier, PLGA.
Int J Nanomedicine. 2011; 6:1685–1697.ii Lee, H., Ahn, C., and Park, T. G. 2009.
“Polylactic-co-(glycolic acid)-Grafted Hyaluronic Acid Copolymer MicelleNanoparticles for Target-Specific Delivery of Doxorubicin.” Macromol. Biosci.9: 336-42.iii Kumar R , Buttar H , Jain V. K.
, Jain N . CurcuminNanoparticles: Preparation, Characterization, and Antimicrobial Study. J.Agric. Food Chem., 2011, 59 (5), pp 2056–2061.