Lactic Acid Nanoparticles Research Articles

Antitumor effect of poly lactic acid nanoparticles loaded with cisplatin and chloroquine on the oral squamous cell carcinoma.

Purpose: Poly lactic acid (PLA) combined with cisplatin-chloroquine nanoparticles (CDDP/CQ-PLA NPs) and PLA combined with cisplatin nanoparticles (CDDP-PLA NPs) were prepared to investigate their inhibitory effects on the proliferation of oral squamous cell carcinoma (OSCC) Cal-27cell line.Patients and methods: We prepared CDDP/CQ-PLA NPs and CDDP-PLA NPs. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to detect the physiological characteristics and particle size parameters of drug-loaded nanoparticles. The drug concentration and cumulative release were measured by UV and visible spectrophotometer. MTT assay was used to detect viability of Cal-27 cells. Annexin/PI staining was used to detect cell apoptosis. Biological kits were used to detect malondialdehyde (MDA) content, catalase (CAT) activity, antioxidant enzyme superoxide dismutase (SOD) activity and glutathione peroxidase (GSH PX) activity in Cal-27 cells. Western blot was used to detect apoptosis and autophagy of Cal-27 cells.Results: CDDP/CQ-PLA NPs and CDDP -PLA NPs had good drug loaded nanoparticles and drug release. CDDP/CQ-PLA NPs showed higher ROS and apoptosis rate, and lower autophagy than CDDP-PLA NPs.Conclusion: CDDP/CQ-PLA NPs reduced autophagy and enhanced ROS and apoptosis of Cal-27 cells, which shows a potential in the clinical treatment of OSCC.

Development and in vitro characterization of diazepam loaded PLA nanoparticles

Diazepam is one of the most frequently used benzodiazepines (BZs) in cancer patients for its desirable psychotropic effects. In this study we tried to explore Diazepam as a repurposed drug and tested it in Neuroblastoma (Neuro 2a) cells. Diazepam loaded Poly Lactic Acid Nanoparticles were developed (D-PLA-NPs) using nanoprecipitation method. Entrapment efficiency was found to be ± 99.7% and drug loading was ± 12.88%. The particle size developed was 188.8 nm and zeta potential was −25.6 millivolt. Dissolution profiles were studied in PBS (pH 7.4) or simulated media, almost 50% release was observed within 6 h. In vitro, cytotoxicity was analyzed using MTT assay where dose-dependent cytotoxicity was observed for developed D-PLA-NPs.

Cardioprotective Effects of Curcumin-Nisin Based Poly Lactic Acid Nanoparticle on Myocardial Infarction in Guinea Pigs

Myocardial infarction (MI) is the most prevalent cause of cardiovascular death. A possible way of preventing MI maybe by dietary supplements. The present study was thus designed to ascertain the cardio-protective effect of a formulated curcumin and nisin based poly lactic acid nanoparticle (CurNisNp) on isoproterenol (ISO) induced MI in guinea pigs. Animals were pretreated for 7 days as follows; Groups A and B animals were given 0.5 mL/kg of normal saline, group C metoprolol (2 mg/kg), groups D and E CurNisNp 10 and 21 mg/kg respectively (n = 5). MI was induced on the 7th day in groups B-E animals. On the 9th day electrocardiogram (ECG) was recorded, blood samples and tissue biopsies were collected for analyses. Toxicity studies on CurNisNp were carried out. MI induction caused atrial fibrillation which was prevented by pretreatment of metoprolol or CurNisNp. MI induction was also associated with increased expressions of cardiac troponin I (CTnI) and kidney injury molecule-1 (KIM-1) which were significantly reduced in guinea pig’s pretreated with metoprolol or CurNisNp (P < 0.05). The LC50 of CurNisNp was 3258.2 μg/mL. This study demonstrated that the formulated curcumin-nisin based nanoparticle confers a significant level of cardio-protection in the guinea pig and is nontoxic.

Development of sonosensitive Poly-(L)-lactic acid nanoparticles

Abstract Due to serious side effects of traditional chemotherapeutic treatment, novel treatment techniques like targeted drug delivery, which allows a reduction of the overall dosage of drugs, are investigated. It is worth mentioning that at the same time, precise drug delivery offers an increased dosage of chemotherapeutic drugs in the tumorous area employing the EPR effect. Therefore, vehicles smaller than 400 nm can be used to pass the poorly aligned endothelial cells of tumour vessels passively through their fenestrations. In a subsequent step, the chemotherapeutic drugs need to be released. One possibility is an ultrasound-based release via inertial cavitation. Thereby, it is desirable to restrict the drug release to a narrow range. Thus, the cavitation inducing ultrasound wave has to be focused to that region of interest. Ultrasound frequencies of more than 500 kHz enable sufficient focusing, however, inertial cavitation occurs primarily at much lower frequencies. In order to afford inertial cavitation at 500 kHz, either bigger particles in the range of micrometres are needed as cavitation nucleus, which is not possible due to the EPR effect or high acoustic pressure is needed to generate inertial cavitation. Nevertheless, this high pressure is inappropriate for clinical applications due to thermal and mechanical effects on biological tissue. We have produced Poly-(L)-lactic acid (PLLA) nanoparticles by a solvent evaporation technique that serve as nucleus for inertial cavitation at moderate acoustic pressure of 800 kPa and at high frequencies of 800 kHz after the particles have been freeze-dried. In this contribution, we characterize the designed particles and present the production process. Moreover, we show that these particles enable inertial cavitation at an acoustic pressure and at acoustic frequencies which are commonly used in clinical ultrasound units. We also show that other particles with the same size at the same acoustic parameters do not induce cavitation activity.

Tamoxifen citrate-loaded poly(d,l) lactic acid nanoparticles: Evaluation for their anticancer activity in vitro and in vivo

The optimization of tamoxifen citrate entrapment and its release from biodegradable poly(d,l) lactic acid nanoparticles are prepared by modified spontaneous emulsification solvent diffusion method. Since the addition of tamoxifen citrate induces the formation of drug crystals from nanoparticle suspension the influence of several parameters on tamoxifen citrate encapsulation was investigated. In vitro studies for cytotoxicity, DNA ladder, and the expression of Bcl-2-Bax expression were also investigated for MCF-7 and MDA-MB-231 cells after the addition of tamoxifen citrate alone and tamoxifen citrate-poly(d,l) lactic acid-nanoparticles (encapsulated tamoxifen citrate). From results, it was noticed that the size and zeta potential of the drug loaded nanoparticles were not differed much in their physicochemical properties from drug free counterparts. The drug-loaded and drug-free nanoparticles exhibited size of in between 271.4 and 282.7 nm and zeta potential of -34 to -27.4 mV, respectively. There was significant increase in drug incorporation in the particles noticed in dichloromethane + methanol system in comparison to acetone + methanol and ethyl acetate + methanol systems. The drug was partly released from the nanoparticles after 48 h of incubation at 37℃. From Fourier transform infrared spectroscopy and differential scanning calorimetry data demonstrated drug-polymer characteristics within the nanoparticles and unincorporated drug that appeared in the form of crystals from polarized microscopic study. MCF-7 and MDA-MB-231 cells were more sensitive to tamoxifen citrate-poly(d,l) lactic acid-nanoparticles than tamoxifen citrate alone. DNA ladder and the expression of Bax to Bcl-2 ratio were much higher in tamoxifen citrate encapsulated in nanoparticles than that in tamoxifen citrate alone. These results demonstrated the feasibility of encapsulation of tamoxifen citrate and its enhanced efficiency in vitro and in vivo studies.

Development of nanoformulation of picroliv isolated from Picrorrhiza kurroa.

Picroliv, a mixture of picroside I and kutkoside isolated from rhizome of Picrorrhiza kurroa has been reported for many pharmaceutical properties such as hepatoprotective, anticholestatic, antioxidant and immune-modulating activity. However, picroliv possessed lesser efficacy due to its poor aqueous solubility and lesser bioavailability. To find solution, picroliv was loaded into biodegradable poly lactic acid nanoparticles (PLA NPs) using solvent evaporation method. The picroliv-loaded PLA NPs were characterised by UV-vis spectroscopy, atomic force microscopy, transmission electron microscopy, Fourier transform infrared and Zeta sizer. The size of picroliv-loaded PLA NPs was 182 ± 20 nm. Zeta potential of picroliv-loaded PLA NPs was -23.5 mV, indicated their good stability. In vitro picroliv release from picroliv-loaded PLA NPs showed an initial burst release followed by slow and sustained release. The efficacy of picroliv-loaded PLA NPs was assessed against KB cell lines. Blank PLA NPs showed no cytotoxicity on KB cells. The picroliv-loaded PLA NPs showed more cytotoxic activity on KB cells as compared to the pure drug. Hence, the developed picroliv nanoformulation would find potential application in pharma-sector.

Infra Red Dye and Endostar Loaded Poly Lactic Acid Nano Particles as a Novel Theranostic Nanomedicine for Breast Cancer.

Endostar, a novel recombinant human endostatin, has been proven to inhibit tumor angiogenesis and is utilized as an anticancer drug. While free drugs can display limited efficacy, nanoscaled anticancer drugs have been fabricated and proven to possess superior therapeutic effects. Poly(lactic acid) (PLA) is a FDA-approved biomaterial displaying excellent biocompatibility and low toxicity. In this study, Endostar-loaded PLA nanoparticles (EPNPs) were first prepared, and a near-infrared (NIR) dye, IRDye 800CW, was conjugated to the surface for detecting nanoparticle biodistribution through fluorescence molecular imaging (FMI) using an orthotopic breast tumor mouse model. The antitumor efficacy of EPNPs was examined using bioluminescence imaging (BLI) and immunohistology. To further improve the antitumor effects, we combined EPNPs with zoledronic acid monohydrate (ZA), which is known to decrease the tumor-associated macrophages (TAM) and inhibit tumor progression. We found that EPNPs decreased human umbilical vein endothelial cell (HUVEC) viability by inhibiting tumor growth gene expression more significantly than free Endostar in vitro. In vivo, EPNPs displayed better tumor growth inhibitory effects compared with free Endostar, and the combination of EPNPs with ZA exhibited more significant antitumor effects. As confirmed by CD31 and CD11b immunohistochemistry, the combination of EPNPs and ZA showed synergistic effects in reducing tumor angiogenesis and TAM accumulation in tumor regions. Taken together, this study presents a novel and effective form of nanoscaled Endostar for the treatment of breast cancer that displays synergistic antitumor effects in combination with ZA.

Fabrication and Characterization of Genistein Encapsulated Poly (D, L) Lactic acid Nanoparticles for Pharmaceutical Application

Phytoestrogens are the most important therapeutic molecules that are richly present in soya based foods. Genistein (GEN) is one among the prominent constituent of soybean. Isolated form of Genistein has poor bioavailability because of its low aqueous solubility, absorption and limited clinical efficacy. Encapsulated GEN could be used for colloidal drug delivery for the treatment of diseases including breast cancer. In the present study we have prepared poly lactic acid based nanoparticles with Genistein by emulsion diffusion method. The obtained genistein-loaded nanoparticles (GEN-PLA-NPs) were characterized for their size (PCS/ Zetasizer), shape (SEM) and other physical properties using FTIR and DSC. Encapsulation efficiency, release characteristics The sizes of the particles were ranged between 100 nm and 380 nm due to different solvents that were used during the preparation of nanoparticles. Under optimal conditions, different sizes of the particles (259.7 nm, 122.3 nm and 105.7 nm) were formed with encapsulation efficiency (73.9&percnt;, 57.9&percnt; and 61.4&percnt;, respectively). The drug and polymer interaction studies were performed by FTIR and DSC. When percent release of encapsulated drug was studies in PBS (pH 7.4), it was found to be biphasic pattern (Korsmeyer-Peppas model) with 21.27&percnt; release at 37°C in 24 h. In hemolysis experiment, Genistein loaded poly (lactic acid) nanoparticles exhibited non-toxic nature. These results demonstrated the feasibility of encapsulation of GEN and its non-toxic in vitro studies. Keywords: Phytoestrogen, sonication, crystallization, Fickian diffusion, hemolysis.