Controlled release of drug and better bioavailability using poly(lactic acid-co-glycolic acid) nanoparticles.

Tamoxifen (Tmx) embedded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA-Tmx) is prepared to evaluate its better DNA cleavage potential, cytotoxicity using Dalton's lymphoma ascite (DLA) cells and MDA-MB231 breast cancer cells. PLGA-Tmx nanoparticles are prepared through emulsified nanoprecipitation technique with varying dimension of 17-30nm by changing the concentrations of polymer, emulsifier and drug. Nanoparticles dimension are measured through electron and atomic force microscopy. Interactions between tamoxifen and PLGA are verified through spectroscopic and calorimetric methods. PLGA-Tmx shows excellent DNA cleavage potential as compared to pure Tmx raising better bioavailability. In vitro cytotoxicity studies indicate that PLGA-Tmx reduces DLA cells viability up to ∼38% against ∼15% in pure Tmx. Hoechst stain is used to detect apoptotic DLA cells through fluorescence imaging of nuclear fragmentation and condensation exhibiting significant increase of apoptosis (70%) in PLGA-Tmx vis-à-vis pure drug (58%). Enhanced DNA cleavage potential, nuclear fragmentation and condensation in apoptotic cells confirm greater bioavailability of PLGA-Tmx as compared to pure Tmx in terms of receptor mediated endocytosis. Hence, the sustained release kinetics of PLGA-Tmx nanoparticles shows much better anticancer efficacy through enhanced DNA cleavage potential and nuclear fragmentation and, thereby, reveal a novel vehicle for the treatment of cancer.

Synthesis and in vitro evaluation of melatonin entrapped PLA nanoparticles: an oxidative stress and T-cell response using golden hamster.

This study was carried out to evaluate the effects of melatonin entrapped PLA nanoparticles (Mel-NPs) and pure Mel on impact of reactive oxygen species (ROS), blastogenic responses (%SR) in terms of proliferation of splenocytes. ROS have been proposed to play an important role in balancing the pro- and antioxidant homeostasis during different physiological condition of organism. Melatonin has been suggested as an effective free radical scavenger that may have an important role during this process. Mel-NPs were prepared by using emulsification (o/w) nanoprecipitation method and their physicochemical characterizations were studied for evaluation of particle size and encapsulation efficiency by using SEM, TEM, particle size analyzer, DSC and FTIR. The TEM micrograph showed excellent findings regarding size, shape, encapsulation efficiency and difference between pure PLA nanoparticles and Mel-NPs. The SEM micrographs of Mel-NPs showed spherical shape, smooth surfaces and the homogeneous particle size distribution. In TEM micrograph, the average diameter of Mel-NPs was found to be 36 ± 8 nm with ∼78% (w/w) of entrapment efficiency. The size of pure PLA nanoparticles was found to be larger as compared to Mel-NPs which confirm that the drug supports the reduction of the size of Mel-NPs. In in vitro study, we observed that Mel-NPs significantly reduce the level of ROS in splenocytes and increased the level %SR at 96 h of splenocytes culture as compared to the culture with pure Mel. Thus our results propose high clinical value for improvement of depressed immunity by Mel-NPs.

Anti-cancer evaluation of quercetin embedded PLA nanoparticles synthesized by emulsified nanoprecipitation.

This study was carried out to synthesize quercetin (Qt) embedded poly(lactic acid) (PLA) nanoparticles (PLA-Qt) and to evaluate anti-cancer efficacy of PLA-Qt by using human breast cancer cells. PLA-Qt were synthesized by using novel emulsified nanoprecipitation technique with varying dimension of 32 ± 8 to 152 ± 9 nm of PLA-Qt with 62 ± 3% (w/w) entrapment efficiency by varying the concentration of polymer, emulsifier, drug and preparation temperature. The dimension of PLA-Qt was measured through transmission electron microscopy indicating larger particle size at higher concentration of PLA. The release rate of Qt from PLA-Qt was found to be more sustained for larger particle dimension (152 ± 9 nm) as compared to smaller particle dimension (32 ± 8 nm). Interaction between Qt and PLA was verified through spectroscopic and calorimetric methods. Delayed diffusion and stronger interaction in PLA-Qt caused the sustained delivery of Qt from the polymer matrix. In vitro cytotoxicity study indicate the killing of ∼ 50% breast cancer cells in two days at 100 µg/ml of drug concentration while the ∼ 40% destruction of cells require 5 days for PLA-Qt (46 ± 6 nm; 20mg/ml of PLA). Thus our results propose anticancer efficacy of PLA-Qt nanoparticles in terms of its sustained release kinetics revealing novel vehicle for the treatment of cancer.

Therapeutic efficacy and toxicity of tamoxifen loaded PLA nanoparticles for breast cancer.

This study was carried out to assess the therapeutic efficacy and toxicity of tamoxifen (Tmx) loaded poly(d,l-lactic acid) (PLA) nanoparticles (Tmx-NPs) for breast cancer. An in vivo study was conducted to determine the effect of Tmx-NPs on DMBA induced mammary tumor in female Wistar rat. The experimental results showed that the mean diameter of Tmx-NPs was 224 ± 3 nm with 68 ± 2% (w/w) of entrapment efficiency. In in vivo study, the tumor size in rat was significantly reduced (P < 0.001) by treating Tmx-NPs as compared to pure Tmx and untreated group (control DMBA). Tmx-NPs showed the marked reduction in hepatotoxicity and renal toxicity when compared to pure Tmx as evidenced by histopathological examination of liver and kidney tissues as well as estimation of AST, ALT levels, and creatinine, urea, blood urea nitrogen levels. Oxidative stress and lipid peroxidation was estimated in spleen, liver and kidney and was found significantly high in pure Tmx treated group as compared to Tmx-NPs and control group. Immunological parameters like blastogenic response of splenocytes, TLC, DLC were studied and found significantly high in pure Tmx treated group but the variations were nonsignificant in Tmx-NPs group as compared to control. Thus, Tmx-NPs have significant therapeutic efficacy with reduced side effects.