Carboplatin-loaded surface modified-PLGA nanoparticles confer sustained inhibitory effect against retinoblastoma cell in vitro

Clarithromycin (CLR) is a member of the macrolide antibiotic group. CLR has low systemic oral bioavailability and is a drug of class II of the Biopharmaceutical Classification System. In many studies, using nanoparticles (NPs) as a drug delivery system has been shown to increase the effectiveness and bioavailability of active drug substances. This study describes the development and evaluation of poly (lactic-co-glycolic acid) (PLGA) NPs and chitosan (CS)-coated PLGA NPs for oral delivery of CLR. NPs were obtained by nanoprecipitation technique and characterized in detail, and the effect of three molecular weights (Mw1: 7.000–17.000, Mw2: 38.000–54.000, Mw3: 50.000–190.000) of PLGA and CS coating on particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), and release properties etc. were elucidated. Gastrointestinal stability and cryoprotectant effect tests were performed on the NPs. The PS of the prepared NPs were in the range of 178 to 578 nm and they were affected by the Mw and CS coating. In surface-modified formulations with CS, the ZP of the NPs increased significantly to positive values. EE% varied from 62% to 85%, depending upon the Mw and CS coating. In vitro release studies of CLR-loaded NPs showed an extended release up to 144 h. Peppas–Sahlin and Weibull kinetic model was found to fit best for CLR release from NPs. By the broth microdilution test method, the antibacterial activity of the formulations was determined on Staphylococcus aureus (ATCC 25923), Listeria monocytogenes (ATCC 1911), and Klebsiella pneumoniae (ATCC 700603). The structures of the formulations were clarified by thermal (DSC), FT-IR, and 1H-NMR analysis. The results showed that PS, ZP, EE%, and dissolution rates of NPs were directly related to the Mw of PLGA and CS coating.

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PLGA nanoparticles as a platform for vitamin D-based cancer therapy

Beilstein Journal of Nanotechnology ◽

10.3762/bjnano.6.135 ◽

2015 ◽

Vol 6 ◽

pp. 1306-1318 ◽

Cited By ~ 23

Author(s):

Maria J Ramalho ◽

Joana A Loureiro ◽

Bárbara Gomes ◽

Manuela F Frasco ◽

Manuel A N Coelho ◽

...

Keyword(s):

Vitamin D ◽

Cell Growth ◽

Cancer Cell ◽

Active Form ◽

A549 Cells ◽

Inhibitory Effect ◽

Plga Nanoparticles ◽

Lung Cancer Cell Line ◽

Pancreatic Cell

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were studied as drug delivery vehicles for calcitriol, the active form of vitamin D3. In vitro effects of calcitriol encapsulated in PLGA nanoparticles were evaluated with respect to free calcitriol on human pancreatic cell lines, S2-013 and hTERT-HPNE, and the lung cancer cell line A549. Encapsulated calcitriol retained its biological activity, reducing the cell growth. Cytotoxicity assays demonstrated that encapsulation of calcitriol enhanced its inhibitory effect on cell growth at a concentration of 2.4 μM for the S2-013 cells (91%) and for A549 cells (70%) comparared to the free calcitriol results. At this concentration the inhibitory effect on nontumor cells (hTERT-HPNE) decreased to 65%. This study highlights the ability of PLGA nanoparticles to deliver vitamin D3 into cancer cells, with major effects regarding cancer cell cycle arrest and major changes in the cell morphological features.

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Homologous and Mitochondrial Targeting Synergistic Induction of Apoptosis and Ferroptosis Enhanced PDT Performance Against Osteosarcoma HOS

10.21203/rs.3.rs-779156/v1 ◽

2021 ◽

Author(s):

Yang Wang ◽

Liang Zhang ◽

Guosheng Zhao ◽

Yuan Zhang ◽

Fangbiao Zhan ◽

...

Keyword(s):

Cell Line ◽

Molecular Mechanisms ◽

Near Infrared ◽

Inhibitory Effect ◽

Plga Nanoparticles ◽

Mitochondrial Targeting ◽

Dual Targeting ◽

Poly Ethylene

Abstract Background: There have been no prominent advancements in osteosarcoma (OS) treatment in the past 20 years. Although photodynamic therapy (PDT) is an emerging technique for cancer therapy, its lack of targeting in OS treatment severely limits its applications.Methods: In this study, we constructed a potential theranostic nanoplatform by using (poly (ethylene glycol) polylactic-co-Glycolic acid (PEG-PLGA) nanoparticles (NPs) wrapping IR780 into the core (PEG-PLGA-IR780 NPs), which was further camouflaged with human OS cell membranes from the HOS cell line (MH-PEG-PLGA-IR780 NPs) to show homologous and mitochondrial targeting capacities. In addition, the potential underlying anticancer mechanisms of MH-PEG-PLGA-IR780 NPs-mediated PDT was investigated.Results: We demonstrated that the MH-PEG-PLGA-IR780 NPs had excellent tumor/mitochondrial targeting with the help of homologous targeting to HOS cell line. Moreover, the excellent photoacoustic (PA)/fluorescence (FL) imaging ability of MH-PEG-PLGA-IR780 NPs laid a foundation for further applications. Under near-infrared (NIR) irradiation, we demonstrated that dual-targeting NPs-mediated PDT could significantly induce HOS cell apoptosis and ferroptosis, and further explored apoptosis was triggered by cytochrome c-activated mitochondrial apoptosis (endogenous apoptosis), and the specific molecular mechanisms of ferroptosis is the activation of NCOA4-mediated ferritinophagy and the passivation of GPX4 in vitro, synergistically leading to the excessive accumulation of ROS. In addition, MH-PEG-PLGA-IR780 NPs-induced PDT also showed an obvious inhibitory effect on tumor growth in vivo. Conclusion: These results suggest the dual-targeting-based theranostic nanoplatform provides an effective method to improve PDT performance in OS and paves a new and promising way for OS therapy.

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Ligand Decorated Embelin Loaded PLGA Nanoparticles for Management of Alcohol Induced Hepatotoxicity

Journal of Drug Delivery and Therapeutics ◽

10.22270/jddt.v10i1.3844 ◽

2020 ◽

Vol 10 (1) ◽

pp. 72-80

Author(s):

Ajay Kumar ◽

M. Nikhat Khan ◽

Jovita Kanoujia ◽

Amandeep Singh ◽

Neeraj Mishra

Keyword(s):

High Performance ◽

In Vitro Release ◽

Plga Nanoparticles ◽

Hep G2 ◽

Release Studies ◽

Plga Nanoparticle ◽

Surface Modified ◽

Vitro Release

Preparation of surface modified Embelin loaded nanoparticles (GA-PEG-PLGA) for the management of hepatotoxicity. Surface modified Embelin loaded GA-PEG-PLGA NPs were evaluated by NMR, FTIR, TEM techniques and in vitro release studies. The biodistribution of the nanoparticles was assessed by High-performance liquid chromatography (HPLC), and the cellular uptake study was evaluated using Hep G2 cells (liver cells lines). The hepatoprotecttive effect of the surface modified Embelin loaded GA-PEG-PLGA NPs was investigated in-vitro and in-vivo. The surface modified Embelin loaded GA-PEG-PLGA nanoparticles significantly increases the uptake of drug in liver by 2.5 folds more than plain drug. Keywords: Glycyrrhetinic acid, Receptor mediated, Surface functionalization, Embelin, PLGA nanoparticle.

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Chitosan surface modified PLGA nanoparticles loaded with brigatinib for the treatment of non-small cell lung cancer

Journal of Polymer Engineering ◽

10.1515/polyeng-2019-0265 ◽

2019 ◽

Vol 39 (10) ◽

pp. 909-916 ◽

Cited By ~ 3

Author(s):

Muqtader Mohammed ◽

Mansour S. Alnafisah ◽

Md. Khalid Anwer ◽

Farhat Fatima ◽

Bjad K. Almutairy ◽

...

Keyword(s):

Lung Cancer ◽

Particle Size ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Plga Nanoparticles ◽

Small Cell ◽

Cancer Site ◽

Small Cell Lung ◽

Surface Modified

Abstract In the current study, surface-modified poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) of brigatinib (BRB) were prepared by studying the variables PLGA (polymer), PVA (stabilizer) and chitosan (coater) against experimentally obtained responses. The optimized NPs (F2) were evaluated in vitro for differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), particle size, polydispersity index (PDI) and drug entrapment (EE), in vitro release, hematocompatibility and in vitro anticancer studies. The optimized NPs’ (F2) composition, PLGA (75 mg), PVA (0.55% w/v), chitosan (0.75% w/v) and 30 mg of BRB was found to be optimum with particle size (406.3 ± 5.1 nm), PDI (0.277), ζ potential (30.4 ± 3.3 mV) and %EE (82.32%). The in vitro release profile showed a sustained release pattern of the F2 nanoparticles of BRB. The 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay revealed a significant anticancer activity for F2 NPs against A549 cell lines in comparison to free BRB. The result obtained in this work indicated the immense potential of nanoparticles to effectively deliver the BRB to the cancer site for the treatment of non-small cell lung cancer.

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Development of tamoxifen‐loaded surface‐modified nanostructured lipid carrier using experimental design: in vitro and ex vivo characterisation

IET Nanobiotechnology ◽

10.1049/iet-nbt.2019.0276 ◽

2020 ◽

Vol 14 (4) ◽

pp. 261-274 ◽

Cited By ~ 1

Author(s):

Ganesan Poovi ◽

Narayanasamy Damodharan

Keyword(s):

Experimental Design ◽

Ex Vivo ◽

Nanostructured Lipid Carrier ◽

Loaded Surface ◽

Surface Modified

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Inhibiting the Progression of Human Retinoblastoma Cell by Downregulation of MMP-2/MMP-9 Using Short Hairpin RNAs (shRNAs) In Vitro

Journal of Ophthalmology ◽

10.1155/2020/4912347 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Nana Meng ◽

Zhi Zhao ◽

Chunhe Shi ◽

Leizhou Xia

Keyword(s):

Cell Cycle ◽

Cell Viability ◽

Mtt Assay ◽

Annexin V ◽

Inhibitory Effect ◽

Flow Cytometer ◽

Migration And Invasion ◽

Retinoblastoma Cell ◽

Human Retinoblastoma

Objective. To investigate the effect of downregulated matrix metalloproteinases (MMPs) gene on the proliferation, apoptosis, cell cycle, migration, and invasion of human retinoblastoma (RB) cell line in vitro. Methods. Small hairpin RNA (shRNA) targeting MMP-2/MMP-9 was designed and transfected into WER1-Rb-1 cells. 48 hours after transfection, qRT-PCR and western blot technique were used to investigate the inhibitory effect of MMP-2 and MMP-9 shRNAs. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle arrest was detected using a flow cytometer while apoptosis was tested with Annexin V/PI kit. Transwell chamber assay was performed to detect the migration and invasion ability of the WER1-Rb-1 cells. Results. After transfection of MMP-2/MMP-9 shRNA, there was a significant decrease in the expressions of both mRNA and protein in the shRNA groups compared with the negative and vector controls. The results of MTT assay suggested that the cell viability was significantly decreased in shRNA groups (p<0.05). Cell apoptosis also increased significantly in shRNA groups compared with the negative and vector controls (p<0.05). The flow cytometer analysis proved that the proportion of the G1 phase increased and the proportion of the G0 phase reduced significantly by the transfection of MMP-2/MMP-9 shRNA (p<0.05). The migration and invasion ability were also significantly decreased in the groups of MMP-2/MMP-9 shRNA (p<0.05). Conclusions. Cell viability, migration, and invasion ability of RB cells are inhibited, and apoptosis is induced after downregulation of MMP-2/MMP-9 through RNA interference. MMP-2 and MMP-9 may be potential targets in the gene therapy of RB.

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Resveratrol-loaded PLGA nanoparticles: enhanced stability, solubility and bioactivity of resveratrol for non-alcoholic fatty liver disease therapy

Royal Society Open Science ◽

10.1098/rsos.181457 ◽

2018 ◽

Vol 5 (11) ◽

pp. 181457 ◽

Cited By ~ 23

Author(s):

Shuqian Wan ◽

Long Zhang ◽

Yunyun Quan ◽

Kun Wei

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Water Solubility ◽

Drug Loading ◽

Inhibitory Effect ◽

Plga Nanoparticles ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

Resveratrol (3, 4′, 5-trihydroxy- trans -stilbene, RSV), a nutraceutical, has recently attracted lots of attention because of its outstanding pharmacological potential. The effects of RSV on non-alcoholic fatty liver disease (NAFLD) remain inconclusive, although a wealth of research has been done. The major obstacle presented was RSV's poor bioavailability due to its poor aqueous solubility, chemical instability and intestinal metabolism. In this study, nanotechnology was used to encapsulate RSV to enhance its stability, water solubility and bioactivity, which can be used to treat NAFLD by HepG2 hepatocytes-induced in vitro . RSV-loaded poly ( d , l -lactide-co-glycolide acid) (PLGA) nanoparticles (RSV-PLGA-NPs) were prepared according to an oil/water (O/W) emulsion technique. The RSV-PLGA-NPs were of spherical morphology with an average size of 176.1 nm and a negative charge of −22.6 mV. These nanoparticles exhibited remarkable encapsulation efficiency (EE%) (97.25%) and drug loading (14.9%) for RSV. A sustained RSV release from RSV-PLGA-NPs could be achieved especially in acidic conditions when simulating transporting through the gastrointestinal tract. In addition, these nanoparticles were stable enough to store at 4°C for a least six months with unchanged EE%. Moreover, RSV-PLGA-NPs were more efficient in alleviating lipogenesis, promoting lipolysis and reducing hepatocellular proliferation than free RSV due to its improved stability, water solubility and bioactivity. These findings indicated that the RSV-PLGA-NPs provided superb and stable drug delivery with small particle size, high capsulation efficiency, well-controlled drug release, which greatly enhanced the stability, water solubility and bioactivity. Besides, the discovery that the inhibitory effect of RSV-PLGA-NPs on hepatocellular proliferation and lipid accumulation in steatotic HepG2 cells may provide a new way to study the mechanism of NAFLD. Therefore, RSV-PLGA-NPs have a promising potential for NAFLD therapy.

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