Dexketoprofen trometamol-loaded poly-lactic-co-glycolic acid (PLGA) nanoparticles: Preparation, <i>in vitro</i> characterization and cyctotoxity

Apoptosis signaling pathways, drug resistance, and metastasis are important targets to develop new cancer treatments. We developed cholesterol-coated Poly(d,l-Lactide-co-Glycolic Acid) (PLGA) nanoparticles for effective encapsulation and delivery of retinoic acid and oxaliplatin to analyze their antitumor activity in colorectal cancer. The cell viability and proliferation of tumoral cells lines (CT-26 and SW-480) decreased when compared to control in vitro after treatment with the nanoparticles. In addition, apoptosis of CT-26 cells increased. Importantly, cytoprotection of nontumor cells was detected. Expression of pro-apoptotic proteins was upregulated, while anti-apoptotic proteins were downregulated either in vitro or in vivo. In addition, drug resistance and metastasis factors were downregulated in vivo. Human colorectal tumors that highly expressed BCL-2 and Ki-67 had a greater tendency towards death within 60 months. Our results show that loading oxaliplatin combined with retinoic acid and cholesterol in a nanoparticle formulation enables determination of optimal antitumor activity and subsequent treatment efficacy.

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EGFP-EGF1-conjugated poly (lactic-co-glycolic acid) nanoparticles as a carrier for the delivery of CCR2− shRNA to atherosclerotic macrophage in vitro

Scientific Reports ◽

10.1038/s41598-020-76416-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Zhilin Wu ◽

Chen Chen ◽

Jiajia Luo ◽

Jacques R. J. Davis ◽

Bo Zhang ◽

...

Keyword(s):

Glycolic Acid ◽

Cultured Cells ◽

Plga Nanoparticles ◽

Cellular Model ◽

Target Delivery ◽

Cellular Models ◽

Inflammatory Monocytes ◽

Promising Therapeutic Approach ◽

Coumarin 6

AbstractReducing macrophage recruitment by silencing chemokine (C–C motif) receptor 2 (CCR2) expression is a promising therapeutic approach against atherosclerosis. However the transfection of macrophages with siRNA is often technically challenging. EGFP-EGF1-conjugated poly (lactic-co-glycolic acid) (PLGA) nanoparticles (ENPs) have a specific affinity to tissue factor (TF). In this study, the feasibility of ENPs as a carrier for target delivery of CCR2-shRNA to atherosclerotic cellular models of macrophages was investigated. Coumarin-6 loaded ENPs were synthesized using a double-emulsion method. Fluorescence microscopy and flow cytometry assay were taken to examine the uptake of Coumarin-6 loaded ENPs in the cellular model. Then a sequence of shRNA specific to CCR2 mRNA was constructed and encapsulated into ENPs. Target delivery of CCR2-shRNA to atherosclerotic cellular models of macrophages in vitro were evaluated. Results showed more uptake of ENPs by the cellular model than common PLGA nanoparticles. CCR2-shRNA loaded ENPs effectively silenced CCR2 gene in the atherosclerotic macrophages and exhibited a favorable cytotoxic profile to cultured cells. With their low cytotoxicity and efficient drug delivery, ENP could be a useful carrier for target delivery of CCR2-shRNA to inflammatory monocytes/macrophages for the therapy against atherosclerosis.

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Study on the Mechanism of Targeted Poly(lactic-co-glycolic acid) Nano-Delivery Carriers in the Treatment of Hemangiomas

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2021.18689 ◽

2021 ◽

Vol 21 (2) ◽

pp. 1236-1243

Author(s):

Sheng Liao ◽

Jiawen Wu ◽

Zhituo Li ◽

Guobing Cheng ◽

Baitao Lu ◽

...

Keyword(s):

Young Children ◽

Targeted Delivery ◽

Glycolic Acid ◽

Plga Nanoparticles ◽

Vascular Tumors ◽

Western Blot Method ◽

Delivery Vector ◽

Double Staining Method ◽

Infants And Young Children

Hemangiomas, also called infantile hemangiomas (IH), are the most common congenital benign vascular tumors in infants and young children. At present, there are many treatment methods for proliferative hemangiomas, which have different effects and lack predictability. Propranolol has gradually replaced glucocorticoids as the first-line treatment for infants and young children with hemangiomas. However, premature discontinuation is prone to relapse, and the efficacy and safety of medication need to be further studied and determined. The exact pathogenesis of hemangiomas is still unclear. Therefore, in this study, poly(lactic-co-glycolic acid) (PLGA) nanoparticles were used as drug delivery carriers, propranolol was encapsulated, and PLGA-propranolol (PLGA-PP) nanodelivery preparations were prepared and targeted. Anisotropy and pharmacokinetics were preliminary studied. At the same time, after the treatment of HemECs cells with PLGA-PP in gradient concentration in vitro, CCK-8 method was used to detect the cell proliferation, and Anyixin-V/PI double staining method was used to detect the apoptosis rate of cells. The effect of PLGA-PP nano-delivery vector on hemangioma was studied by western blot method to detect the expression level of Id-1 protein in HemECs. The results showed that after PLGA-PP treated HemECs for 24 h, PLGA-PP significantly inhibited HeECs proliferation and promoted their apoptosis, and the intracellular Id-1 protein expression was also reduced. Therefore, this study believes that the mechanism of PLGA-PP nano-targeted delivery preparations in the treatment of hemangiomas is achieved by down-regulating the Id-1 gene, thereby inhibiting the colonization of HemECs and promoting its apoptosis effect.

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Clarithromycin-Loaded Poly (Lactic-co-glycolic Acid) (PLGA) Nanoparticles for Oral Administration: Effect of Polymer Molecular Weight and Surface Modification with Chitosan on Formulation, Nanoparticle Characterization and Antibacterial Effects

Polymers ◽

10.3390/polym11101632 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1632 ◽

Cited By ~ 8

Author(s):

A. Alper Öztürk ◽

Evrim Yenilmez ◽

Mustafa Güçlü Özarda

Keyword(s):

Oral Delivery ◽

Glycolic Acid ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Plga Nanoparticles ◽

Test Method ◽

Molecular Weights ◽

Antibiotic Group ◽

Surface Modified

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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Preparation of Poly[lactic-co-glycolic] Acid Nanospheres and Its Role in Hepatoma Cells

Journal of Nanoscience and Nanotechnology ◽

10.1166/jnn.2021.18627 ◽

2021 ◽

Vol 21 (2) ◽

pp. 977-986

Author(s):

Zhongxing Shi ◽

Jinping Li ◽

Hongwei Liang ◽

Hongbo Hu ◽

Huijie Jiang

Keyword(s):

Particle Size ◽

Release Rate ◽

Hepg2 Cells ◽

Glycolic Acid ◽

Drug Loading ◽

Average Particle Size ◽

Plga Nanoparticles ◽

Toxin Gene ◽

Average Particle

Poly[lactic-co-glycolic] acid (PLGA) targeting nanoparticles AFP/PLGA/Dt386, loaded with Dt386 plasmid of diphtheria toxin gene, modified by Alpha fetoprotein (AFP) monoclonal antibody, is prepared. Its physical and chemical properties and its effect on HepG2 cells are studied. Firstly, Dt386 expression plasmid pET11a/Dt386 is constructed and PLGA nanoparticles are prepared by emulsion solvent evaporation (ESE). Scanning electron microscope (SEM) is used to observe its morphology. Laser Particle Sizer is used to measure the particle size. In addition, the encapsulation efficiency, drug loading and in vitro release rate of PLGA nanoparticles are measured. Carboxy fluorescein and rhodamine fluorescein are used to double label IgG/PLGA/Dt386 and AFP/PLGA/Dt386 nanospheres, respectively, the entry of nanospheres into HepG2 cells are observed at 3 h and 12 h. The effect of AFP/PLGA/Dt386 nanospheres on the migration of HepG2 cells is examined by wounding healing assay. Transwell chamber experiment is used to detect the effect of AFP/PLGA/Dt386 nanospheres on the invasion of HepG2 cells. MTT method is utilized to determine the inhibitory activity of nanoparticles on HepG2 cell proliferation. After treated with IgG/PLGA/Dt386 and AFP/PLGA/Dt386 nanoparticles for 48 hours, flow cytometry is used to detect the apoptosis rate and cell cycle of HepG2 cells in each group. The results show that the prepared nanospheres have regular morphology, flat surface, average particle size of 265.72±12.46 nm, zeta potential of −18.15 mV. The average entrapment efficiency and drug loading are 78.48±1.71% and 3.16±0.35%, respectively. The nanoparticles release slowly and stably in vitro. At the 10th day, the release rate reaches 75.13%. PLGA nanospheres can effectively protect DNA from nuclease degradation. The results show that AFP/PLGA/Dt386 nanospheres have biological targeting effect and can be enriched in cells. AFP/PLGA/Dt386 nanoparticles can significantly inhibit the migration, invasion and proliferation of HepG2 cells, and promote apoptosis.

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513. In Vitro and In Vivo Effects of Composite Calcium Phosphate and Poly(Lactic-Co-Glycolic Acid) (PLGA) Nanoparticles Engineered for Enhanced Cancer Cell Internalization and Sustained siRNA Release

Molecular Therapy ◽

10.1016/s1525-0016(16)34848-1 ◽

2013 ◽

Vol 21 ◽

pp. S198-S199

Keyword(s):

Calcium Phosphate ◽

Cancer Cell ◽

Glycolic Acid ◽

Plga Nanoparticles ◽

Cell Internalization ◽

In Vivo Effects

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Preparation and Release Profiles of a Solid Oleoylchitosan Coated Poly(lactic-co-glycolic acid) Nanoparticles

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.936.717 ◽

2014 ◽

Vol 936 ◽

pp. 717-722

Author(s):

Yan Yan Li ◽

Feng Song Liu

Keyword(s):

Drug Release ◽

Glycolic Acid ◽

Entrapment Efficiency ◽

Plga Nanoparticles ◽

Release Behavior ◽

Release Rates ◽

In Vitro Drug Release ◽

Drug Entrapment Efficiency ◽

Model Drug

A solid oleoylchitosan (OCS) coated Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (OCS-coated PLGA NPs) were prepared using the emulsification–evaporation method. The nanoparticles in suspension (TEM) and solid state (SEM) were spherical and very regular and compact. The effects of OCS concentration, PLGA concentration, drug concentration, and release media on drug entrapment efficiency and in vitro drug release behavior were investigated for the release properties using rifampicin (RFP) as a model drug. Both the increase of PLGA concentration and the increase of OCS concentration could decrease the drug release rates. The RFP release rates decreased as the RFP concentration increased. The RFP release rate was sensitive to the pH of the release media.

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Fabrication and Characterization of Chitosan/Poly(Lactic-Co-glycolic Acid) Core-Shell Nanoparticles by Coaxial Electrospray Technology for Dual Delivery of Natamycin and Clotrimazole

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.635485 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xiaoming Cui ◽

Xiaoli Li ◽

Zhilu Xu ◽

Xiuwen Guan ◽

Jinlong Ma ◽

...

Keyword(s):

Glycolic Acid ◽

Fungal Growth ◽

Plga Nanoparticles ◽

Core Shell ◽

Shell Nanoparticles ◽

Drug Of Choice ◽

Fungal Growth Inhibition ◽

Coaxial Electrospray

Natamycin (NAT) is the drug of choice for the treatment of fungal keratitis (FK). However, its inherent shortcomings, such as poor solubility, high dosing frequency, and long treatment cycle, need to be urgently addressed by designing a new delivery to widen its clinical utility. Growing research has confirmed that clotrimazole (CLZ) plays a significant role in fungal growth inhibition. Hence, coaxial electrospray (CO-ES) technology is used herein to prepare nano-systems with an average hydrodynamic particle size of 309-406 nm for the co-delivery of NAT and CLZ in chitosan (CTS) and poly(lactic-co-glycolic acid) (PLGA). The resulting NAT/CLZ@CTS/PLGA formulations were characterized by a transmission electron microscope (TEM) and in vitro release test. The results show that the formulations had obvious core-shell structures, uniform particle distribution, and also can sustain the release of drugs over 36 h. Furthermore, in vitro hemolysis, in vivo corneal irritation test, local allergenic test, and antifungal activity analyses are performed to evaluate the safety and efficiency of the formulations. Thus, good biosafety along with a significant anti-candidiasis effect are found in the NAT/CLZ@CTS/PLGA nanoparticles (NPs). Taken together, the results suggest that this design may provide a promising drug delivery system and a new option for the treatment of FK.

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Poly-(Lactic-co-Glycolic) Acid Nanoparticles for Synergistic Delivery of Epirubicin and Paclitaxel to Human Lung Cancer Cells

Molecules ◽

10.3390/molecules25184243 ◽

2020 ◽

Vol 25 (18) ◽

pp. 4243 ◽

Cited By ~ 1

Author(s):

Nikita Sharma ◽

R. Mankamna Kumari ◽

Nidhi Gupta ◽

Asad Syed ◽

Ali H. Bahkali ◽

...

Keyword(s):

Lung Cancer ◽

Combination Therapy ◽

Glycolic Acid ◽

Colloidal Stability ◽

P53 Protein ◽

In Vitro Release ◽

Plga Nanoparticles ◽

Human Lung Cancer ◽

Lung Cancer Patients

Combination therapy using chemically distinct drugs has appeared as one of the promising strategies to improve anticancer treatment efficiency. In the present investigation, poly-(lactic-co-glycolic) acid (PLGA) nanoparticles electrostatically conjugated with polyethylenimine (PEI)-based co-delivery system for epirubicin and paclitaxel (PLGA-PEI-EPI-PTX NPs) has been developed. The PLGA-PEI-EPI-PTX NPs exhibited a monodispersed size distribution with an average size of 240.93 ± 12.70 nm as measured through DLS and 70.8–145 nm using AFM. The zeta potential of 41.95 ± 0.65 mV from −17.45 ± 2.15 mV further confirmed the colloidal stability and PEI modification on PLGA nanoparticles. Encapsulation and loading efficiency along with in vitro release of drug for nanoparticles were done spectrophotometrically. The FTIR analysis of PLGA-PEI-EPI-PTX NPs revealed the involvement of amide moiety between polymer PLGA and PEI. The effect of nanoparticles on the cell migration was also corroborated through wound healing assay. The MTT assay demonstrated that PLGA-PEI-EPI-PTX NPs exhibited considerable anticancer potential as compared to the naïve drugs. Further, p53 protein expression analysed through western blot showed enhanced expression. This study suggests that combination therapy using PLGA-PEI-EPI-PTX NPs represent a potential approach and could offer clinical benefits in the future for lung cancer patients.

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Bioavailability of Orally Delivered Alpha-Tocopherol by Poly(Lactic-Co-Glycolic) Acid (PLGA) Nanoparticles and Chitosan Covered PLGA Nanoparticles in F344 Rats

Nanobiomedicine ◽

10.5772/63305 ◽

2016 ◽

Vol 3 ◽

pp. 8 ◽

Cited By ~ 12

Author(s):

Lacey C. Simon ◽

Rhett W. Stout ◽

Cristina Sabliov

Keyword(s):

Zeta Potential ◽

Glycolic Acid ◽

Release Kinetics ◽

Entrapment Efficiency ◽

Plga Nanoparticles ◽

Particle Systems ◽

Alpha Tocopherol ◽

In Vitro Assays ◽

Pharmacokinetic Studies

It is hypothesized that the bioavailability of αT (alpha-tocopherol), an antioxidant, can be improved when delivered by poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) and chitosan covered PLGA nanoparticles (PLGA-Chi NPs), and that the mucoadhesive properties of chitosan may enhance absorption of αT. PLGA and PLGA-Chi NPs were characterized by measuring entrapment efficiency, size, polydispersity, and zeta potential. Nanoparticle physical stability, chemical stability of entrapped αT, and release kinetics were also measured. Pharmacokinetic studies were conducted by administering PLGA (αT) NPs, PLGA-Chi (αT) NPs, and free αT via oral gavage in rats. The size and zeta potential of the two particle systems were 97.87 ± 2.63 nm and −36.2 ± 1.31 mV for PLGA(αT) NPs, and 134 ± 2.05 nm and 38.0 ± 2.90 mV for PLGA-Chi (αT) nanoparticles in DI water. The particle systems showed to be stable during various in vitro assays. Bioavailability of nanodelivered αT was improved compared to the free αT, by 170% and 121% for PLGA and PLGA-Chi NPs, respectively. It was concluded that while chitosan did not further improved bioavailability of αT, PLGA NPs protected the entrapped drug from the GI environment degradation and proved to be an effective delivery system for αT.

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