Enhanced anticancer activity of (-)-epigallocatechin-3-gallate (EGCG) encapsulated NPs toward colon cancer cell lines.

(-)-Epigallocatechin-3-gallate (EGCG), a bioactive polyphenol of green tea, has chemo-preventive effects against various cancer cells. Nanoparticles (NPs) carrying different ligands are able to specifically interact with their receptors on different cancer cells that can provide effective release of cytotoxic drugs. In the present study, we have prepared EGCG entrapped NPs using PLGA (poly(d,l-lactide-co-glycolide)). Polyethylene glycol (PEG) and folic acid (FA) via double emulsion solvent evaporation (DESE) method obtained PLGA-EGCG (P-E), PLGA-PEG-EGCG (PP-E), and PLGA-PEG-FA-EGCG (PPF-E). Nanoformulations had been characterized with 1H NMR and FT-IR techniques, AFM, and DLS. PPF-E NPs showed an average size of 220 nm. Analysis of zeta potential confirmed the stability of NPs. HCT-116, HT-29, HCT-15, and HEK 293 cells were treated with both the prepared NPs and free EGCG (0-140 µM). Result showed PPF-E NPs had improved delivery, uptake and cell cytotoxicity toward human folic acid receptor-positive (FR+) colorectal cancer (CRC) cells as mainly on HCT-116 compared to HT-29, but not on the folic acid-negative cells (FR-) as HCT-15. PPF-E NPs enhanced intracellular reactive oxygen species (ROS) level in absence of N-acetyl-l-cysteine (NAC), elevated DNA fragmentation level, and increased apoptotic cell death at higher doses compared to other two NPs and free EGCG. In conclusion, PPF-E NPs exerted greater efficacy than PP-E, P-E, and free EGCG in HCT-116 cells.

Morin encapsulated chitosan nanoparticles (MCNPs) ameliorate arsenic induced liver damage through improvement of the antioxidant system and prevention of apoptosis and inflammation in mice.

Chronic exposure to arsenic over a period of time induces toxicity, primarily in the liver but gradually in all systems of the body. Morin hydrate (MH; 2',3,4',5,7-pentahydroxyflavone), a potent flavonoid abundantly present in plants of the Moraceae family, is thought to be a major bioactive compound that may be used to prevent a wide range of disease pathologies including hepatotoxicity. Therapeutic applications of morin (MOR) are however seriously constrained because of its insolubility, poor bioavailability, high metabolism and rapid elimination from the human body. Nanoformulation of MOR is a possible solution to these problems. In the present study we investigated the effectiveness of morin encapsulated chitosan nanoparticles (MCNPs) against arsenic induced liver damage in mice. MNCPs with an average diameter of 124.5 nm, a zeta potential of +16.2 mV and an encapsulation efficiency of 78% were prepared. Co-treatment of MOR and MCNPs by oral gavage on alternate days reduced the serum levels of AST, ALT, and ALP that were elevated in arsenic treated mice. The efficiency of MCNPs was found to be nearly 4 times higher than that of free MOR. Haematological and serum biochemical parameters including lipid profiles altered by arsenic were normalized following MCNP treatment. Arsenic deposition was lowered in the presence of MCNPs. Administration of MCNPs markedly inhibited ROS generation and elevated MDA levels in arsenic exposed mice. The level of hepatic antioxidant factors such as nuclear Nrf2 (Nrf2), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), GSH peroxidase (GPx), glutathione-S-transferase (GST), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1(NQO1) were markedly enhanced in the arsenic + MCNP group. Treatment by MCNPs prevented the arsenic induced damage of tissue histology. Also, MCNPs suppressed the arsenic induced pro- and anti-apoptotic parameters and attenuated the level of inflammatory mediators. Our data suggest that MCNPs are good hepatoprotective agents compared to free morin against arsenic induced toxicity and the protective effect results from its strong antioxidant, antiapoptotic and anti-inflammatory properties.

Morin-VitaminE-ß-CyclodextrinInclusionComplexLoadedChitosanNanoparticles (M-Vit.E-CD-CSNPs) Ameliorate Arsenic-Induced Hepatotoxicityina Murine Model.

The special features of cyclodextrins (CDs), hydrophilic outer surfaces and hydrophobic inner surfaces, allow for development of inclusion complexes. The two bioactive strong antioxidant hepatoprotective compounds, Morin and vitamin E, are water insoluble. The present study aimed to prepare Morin-vitamin E-ß-cyclodextrin inclusion complex loaded chitosan nanoparticles (M-Vit.E-CD-CS NPs) and to examine their hepatoprotective efficacy against arsenic-induced toxicity in a murine model. The NPs were characterized by FTIR, DLS, NMR, DSC, XRD, AFM, and a TEM study. The NPs were spherical in shape, 178 ± 1.5 nm in size with a polydispersity index (PDI) value of 0.18 and a zeta potential value of −22.4 ± 0.31 mV, with >50% encapsulation and drug loading efficacy. Mice were exposed to arsenic via drinking water, followed by treatment without or with the NPs on every alternate day up to 30 days by oral gavaging. Administration of NPs inhibited the arsenic-induced elevation of liver function markers, inflammatory and proapoptotic factors, reactive oxygen species (ROS) production, alteration in the level of blood parameters and antioxidant factors, and liver damage, which was measured by different biochemical assays, ELISA, Western blot, and histological study. Organ distribution of nanoparticles was measured by HPLC. M-Vit.E-CD-CS NPs showing potent hepatoprotective activity may be therapeutically beneficial.

Programmed supramolecular nanoassemblies: enhanced serum stability and cell specific triggered release of anti-cancer drugs.

A bolaamphiphilic cross-linked nanoassembly endowed with pH responsive degradation features has been designed and fabricated for stable noncovalent guest encapsulation and controlled release. The self-assembled bolaamphiphile is utilized to prepare cross-linked nanoassemblies to further stabilize the noncovalent guest encapsulation at a concentration below its critical aggregation concentration (CAC) in a large volume of water or serum for drug delivery applications. Thus, this system can simultaneously address premature drug release and safety issues. The nanoassemblies integrated with a ß-thioester linker, which can be hydrolyzed selectively under mildly acidic conditions (pH ∼ 5.3) at a slow rate, thus enable controlled release of guest molecules. Biological evaluation revealed that doxorubicin loaded cross-linked nanoassemblies (CNs-DOX) are nontoxic to normal cells such as HEK-293 or PBMC, but in contrast, showed a robust apoptotic effect on colon cancer cells, HCT-116, indicating excellent specificity. Thus, the fabrication reproducibility, robust stability, triggered drug release and cell selective toxicity behavior make this small molecular system very promising in the field of chemotherapeutic applications.

Green Approach To Synthesize Crystalline Nanoscale ZnII-Coordination Polymers: Cell Growth Inhibition and Immunofluorescence Study.

Five new coordination polymers (CPs) namely, [{Zn(µ2-H2O)0.5(5N3-IPA)(2,2'-bpe)}]∞ (1), [{Zn(µ2-H2O)0.5(5N3-IPA)(1,10-phen)}]∞ (2), [{Zn(5N3-IPA)(1,2-bpe)}]∞ (3), [{Zn(5N3-IPA)(1,2-bpey)}]∞ (4), and [{Zn(H2O)(5N3-IPA)(4,4'-tme)}(H2O)0.5]∞ (5) (5N3-H2IPA = 5-azidoisophthalic acid, 2,2'-bpe= 2,2'-bipyridine, 1,10-phen = 1,10-phenanthroline, 1,2-bpe = 1,2-bis(4-pyridyl)ethane, 1,2-bpey = 1,2-bis(4-pyridyl)ethylene, 4,4'-tme = 4,4'-trimethylenedipyridine), have been synthesized based on a mixed ligand approach adopting a solvothermal technique. Depending upon the intrinsic structural flexibility of the bis-pyridyl coligands, interesting structural topologies have also been observed in the resulting CPs: Sra SrAl2 type topology for 3 and a 3-fold interpenetrated dmp topology for 4. A green hand grinding technique has been implemented to reduce the particle size of the CPs to generate nanoscale CPs (NCPs). SEM studies of NCPs reveal the formation of square and spherical particles for NCP 1 and 2, respectively, and nano rod for NCP 3, 4, and 5. Remarkably, when scaled down to nano range all the NCPs retain their crystalline nature. The cytotoxic activity of the NCPs (1-5) has been studied using human colorectal carcinoma cells (HCT 116). Significant cell death is observed for NCP 2, which is further corroborated by cell growth inhibition study. The observed cell death is likely to be due to mitochondrial-assisted apoptosis as is evident from immunofluorescence study.