Polyalthic Acid in Polymeric Nanoparticles Causes Selective Growth                     Inhibition and Genotoxicity in MCF-7 Cells

Polyalthic acid (PA) is a diterpene present in several trees of the Copaifera genus, with reported antitumor activity but poor water solubility. The aim of this work was the incorporation of PA in polymeric nanoparticles and the evaluation of the antiproliferative activity of this formulation in tumor (MCF-7) and normal (MCF-10A) breast cell lines. The nanoparticles were obtained by nanoprecipitation, using poly lactic-co-glycolic acid (PLGA) as the main material. Scanning electron microscopy showed nanoparticles with semispherical morphology, and dynamic light scattering measures revealed negative surface charge and average size of 98.64 ± 28 nm. The encapsulation efficiency was 98% and the drug loading was 15.6% ± 0.02%. Treatments with PA nanoparticles reduced cell proliferation more efficiently than free PA and the effect was selective on MCF-7 cells. Comet assay revealed a selective DNA damage induction by the nanoformulation on the tumor cells, which probably caused the antiproliferative effect. Our results show that PA incorporated in PLGA nanoparticles has potential as a selective cytostatic and genotoxic agent against MCF-7 cells.

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Effect of Semi-synthetic Andrographolide Analogue-loaded Polymeric Micelles on HN22 Cell Migration

Walailak Journal of Science and Technology (WJST) ◽

10.48048/wjst.2020.5515 ◽

2018 ◽

Vol 17 (2) ◽

pp. 88-95

Author(s):

Teeratas KANSOM ◽

Rungnapha SAEENG ◽

Tanasait NGAWHIRUNPAT ◽

Theerasak ROJANARATA ◽

Prasopchai TONGLAIROUM ◽

...

Keyword(s):

Cell Migration ◽

Water Solubility ◽

Polymeric Micelles ◽

Drug Loading ◽

Spherical Shape ◽

Entrapment Efficiency ◽

Migration Assay ◽

Negative Surface ◽

Negative Surface Charge

Semi-synthetic andrographolide (AG) analogue, namely 19-tert-butyldiphenylsilyl-8,17-epoxy andrographolide, or 3A.1, is an anticancer drug. However, the major problem of 3A.1 is poor water solubility hindering its clinical applications. To improve the water solubility and anticancer potency of this analogue, 3A.1-loaded polymeric micelles employing N-naphthyl-N-O-succinyl chitosan (NSCS) as amphiphilic copolymer were prepared by the dropping method. The morphology, particle size, entrapment efficiency (%EE), and loading capacity (%LC) were evaluated. The 3A.1-loaded NSCS micelles were successfully prepared. These micelles were nano-size (66.26 to 102.53 nm) and with a spherical shape, with negative surface charge (-30.50 to -22.23 mV). The 3A.1-loaded NSCS micelles with 40 % drug loading exhibited the maximum values of both %EE (90.84 %) and %LC (25.95 %), indicating that a high amount of 3A.1 could be entrapped into the NSCS micelles. In addition, in vitro anticancer activity and cell migration assay on HN22 cells were evaluated. The 3A.1-loaded NSCS micelles exhibited stronger anticancer effect and cell migration suppression than the free drug. Therefore, these NSCS micelles containing 3A.1 may be potential nanocarriers for the treatment of oral cancer.

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Preparation and evaluation of a stable and sustained release of lansoprazole-loaded poly(d,l-lactide-co-glycolide) polymeric nanoparticles

Journal of Polymer Engineering ◽

10.1515/polyeng-2019-0164 ◽

2019 ◽

Vol 39 (9) ◽

pp. 822-829 ◽

Cited By ~ 1

Author(s):

Bader B. Alsulays ◽

Md. Khalid Anwer ◽

Mohammed F. Aldawsari ◽

Alhussain Aodah ◽

Elsadig Adam ◽

...

Keyword(s):

Sustained Release ◽

Magnesium Oxide ◽

Polymeric Nanoparticles ◽

Drug Loading ◽

Plga Nanoparticles ◽

Base Peak ◽

Solvent Evaporation Method ◽

Physicochemical Stability ◽

Preparation And Evaluation

Abstract The aim of the study was to prepare lansoprazole (LNS)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles in order to improve the physicochemical stability associated with LNS. We synthesized LNS-loaded PLGA nanoparticles in the presence of magnesium oxide as alkalizer to improve the release of LNS and stability against photodegradation. The LNS-encapsulated PLGA nanoparticles were developed by the nanoprecipitation/solvent evaporation method, resulting in a particle size of 246.7 ± 3.4 nm, polydispersity index (PDI) of 0.126, percent drug entrapment (PDE) of 82.85 ± 4.5%, percent drug loading (PDL) of 3.54 ± 0.34%, and pH of 8.10 ± 0.56. The developed nanoparticles were further evaluated for in vitro release and resistance to photodegradation by NMR spectroscopy and LC-MS. The sustained release of the drug was confirmed after the encapsulation of LNS in the PLGA matrix. The protection of LNS in the PLGA matrix against photodegradation was confirmed by NMR and LC-MS studies. The LC-MS of UV-exposed samples of pure LNS and LNS-loaded PLGA nanoparticles at 254 nm showed the same (M + 1) peak at 370 m/e, and the base peak at 369 m/e accounted for the unchanged structure of LNS inside PLGA nanoparticles. Overall, it was proved that PLGA nanoparticles in the presence of magnesium oxide are an efficient carrier to deliver and protect LNS from physicochemical instability.

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Utilization of Microfluidics for the Preparation of Polymeric Nanoparticles for the Antioxidant Rutin: A Comparison with Bulk Production

Pharmaceutical Nanotechnology ◽

10.2174/2211738507666191019141049 ◽

2019 ◽

Vol 7 (6) ◽

pp. 469-483 ◽

Cited By ~ 3

Author(s):

Hanh T.H. Vu ◽

Sarah Streck ◽

Sarah M. Hook ◽

Arlene McDowell

Keyword(s):

Solid State ◽

Polymeric Nanoparticles ◽

Drug Loading ◽

Entrapment Efficiency ◽

Production Method ◽

Plga Nanoparticles ◽

Burst Release ◽

Biorelevant Media ◽

Nanoprecipitation Method ◽

Bulk Production

Objective: To compare the characteristics of rutin-loaded PLGA (poly(lactic-coglycolic acid)) nanoparticles prepared using a single emulsion evaporation method (bulk method) and a nanoprecipitation method using microfluidics. Method: Rutin-loaded PLGA nanoparticles were produced using different methods and characterized for size, zeta potential, entrapment efficiency (EE) and drug loading (DL). A design of experiments approach was used to identify the effect of method parameters to optimize the formulation. DSC was used to investigate the solid-state characteristics of rutin and PLGA and identify any interactions in the rutin-loaded PLGA nanoparticles. The release of rutin from PLGA nanoparticles was examined in biorelevant media and phosphate buffer (PBS). Results : The optimal formulation of rutin-loaded PLGA nanoparticles produced using a microfluidics method resulted in a higher entrapment efficiency of 34 ± 2% and a smaller size of 123 ± 4 nm compared to a bulk method (EE 27 ± 1%, size 179 ± 13 nm). The solidstate of rutin and PLGA changed from crystalline to amorphous with the preparation of rutin- loaded PLGA nanoparticles. More importantly, using microfluidics, rutin released faster from rutin-loaded PLGA nanoparticles in biorelevant media and PBS with higher burst release compared to the rutin release from the nanoparticles prepared by using the bulk method. Conclusion: Rutin can be encapsulated in nanoparticles formulated with different methods with mean sizes of less than 200 nm. Microfluidics produced more uniform rutin-loaded PLGA nanoparticles with a higher EE, DL and faster release compared to a bulk production method.

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Preparation of wormlike polymeric nanoparticles coated with silica for delivery of methotrexate and evaluation of anticancer activity against MCF7 cells

Journal of Biomaterials Applications ◽

10.1177/0885328217698063 ◽

2017 ◽

Vol 31 (9) ◽

pp. 1305-1316 ◽

Cited By ~ 31

Author(s):

Farhad Gharebaghi ◽

Naser Dalali ◽

Ebrahim Ahmadi ◽

Hossein Danafar

Keyword(s):

Polymeric Nanoparticles ◽

Drug Loading ◽

Free Drug ◽

Spherical Nanoparticles ◽

Mcf7 Cells ◽

Anti Cancer ◽

The Impact ◽

Cancer Activity ◽

Mcf 7

Methotrexate is one of the most effective drugs that is commonly used in the treatment of cancer. However, its application is limited due to low solubility, high toxicity and rapid metabolism. Therefore, in the present study, worm-like polymeric nanoparticles as carrier of methotrexate were prepared using biodegradable copolymers (mPEG–PCL). The impact of nanoparticles’ geometry on the loading, delivery and drug’s anti-cancer activity was investigated. The di-block copolymer mPEG–PCL was being synthesized by a ring opening polymerization of ɛ-caprolactone in the presence of mPEG as the initiator and Sn(oct)2 as the catalyst. It was used for the preparation of worm-like micelles and coated with silica, so that their structures are stable after drying. The synthesized copolymers and nanoparticles were characterized by FTIR, HNMR, GPC, XRD, TGA, DLS, and FE-SEM analyses. The efficiencies of drug loading and release of nanoparticles as in vitro, was studied by high performance liquid chromatography. The MTT method was used to estimate the toxicity on MCF-7 cell category. The obtained results showed that the nanoparticles were worm-like particles with less than 150 nm diameter and about 1 µm length. The loading and encapsulation efficiencies of drug by the worm-like nanoparticles were 3.5 ± 0.14% and 65.6 ± 0.12%, respectively, while they were obtained as 2.1 ± 0.08% and 26 ± 0.10%, respectively, for spherical nanoparticles. The methotrexate diffusional behavior of worm-like nanoparticles was compared with that of the spherical ones. On the other hand, the anti-cancer activity of MTX-loaded nanoparticles was more than the free drug. The results of the MTT assay showed strong and dose-dependent inhibition of cell (MCF-7 category) growth by the nanoparticles compared with MTX. The inhibitory concentrations (IC50 i.e. reduction viability of cell to 50%) obtained for worm-like, spherical nanoparticles and free drug (incubation times 72 h) were 8.25 ± 0.20, 9.15 ± 0.17, 12.28 ± 0.15 µg/mL, respectively. It can be concluded that application of non-spherical nanoparticles is a better and more effective strategy for controlled and slow release of methotrexate in the treatment of cancer.

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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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Folate and Borneol Modified Bifunctional Nanoparticles for Enhanced Oral Absorption

Pharmaceutics ◽

10.3390/pharmaceutics10030146 ◽

2018 ◽

Vol 10 (3) ◽

pp. 146 ◽

Cited By ~ 4

Author(s):

Yifan Yang ◽

Yunzhi Yin ◽

Jun Zhang ◽

Tiantian Zuo ◽

Xiao Liang ◽

...

Keyword(s):

Oral Delivery ◽

Oral Absorption ◽

Oral Drug Delivery ◽

Drug Loading ◽

In Vitro Release ◽

Plga Nanoparticles ◽

Oral Drug ◽

Average Size ◽

Promising Perspective

Oral delivery is considered the preferred route of administration due to its convenience and favorable compliance. Here, docetaxel (DTX) loaded polylactic-co-glycolic acid (PLGA) nanoparticles, coated with polyethyleneimine–folic acid (PEI-FA) and polyethyleneimine–borneol (PEI-BO), were designed to enhance oral absorption (FA/BO-PLGA-NPs). The FA/BO-PLGA-NPs were spherical and smooth with an average size of (137.0 ± 2.1) nm. Encapsulation efficiency (EE%) and drug loading (DL%) were (80.3 ± 1.8)% and (2.3 ± 0.3)%, respectively. In vitro release studies showed that approximately 62.1% of DTX was released from FA/BO-PLGA-NPs in media at pH 7.4. The reverted gut sac method showed that the absorption of FA/BO-PLGA-NPs in the intestines was approximately 6.0 times that of DTX. Moreover, cellular uptake suggested that the obtained FA/BO-PLGA-NPs could be efficiently internalized into Caco-2 cells via FA-mediated active targeting and BO-mediated P-glycoprotein (P-gp) inhibition. Pharmacokinetics study demonstrated that after oral administration of DTX at a dose of 10 mg/kg in FA/BO-PLGA-NPs, the bioavailability of FA/BO-PLGA-NPs was enhanced by approximately 6.8-fold compared with that of DTX suspension. FA/BO-PLGA-NPs caused no obvious irritation to the intestines. Overall, the FA/BO-PLGA-NP formulation remarkably improved the oral bioavailability of DTX and exhibited a promising perspective in oral drug delivery.

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Assessment of Damage to Human Platelets after Aggregation and Other Injuries by Microscopic Observation and Estimation of Serotonin Uptake

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654139 ◽

1970 ◽

Vol 23 (02) ◽

pp. 261-275 ◽

Cited By ~ 3

Author(s):

G Zbinden ◽

J. N Mehrishi ◽

S Tomlin

Keyword(s):

Platelet Aggregation ◽

Electrophoretic Mobility ◽

Human Platelets ◽

Freezing And Thawing ◽

Low Degree ◽

Microscopic Evaluation ◽

Negative Surface ◽

Negative Surface Charge ◽

Charged Macromolecules ◽

5 Ht Uptake

SummaryThe severity of platelet damage induced by hyper- and hypotonic NaCl solutions and freezing and thawing was assessed by microscopic evaluation and measuring inhibition of 5-HT uptake. The same techniques were used to quantitate the effects of aggregating agents. The positively charged macromolecules PS, Poly-L und Poly-O reduced the net negative surface charge as determined by microelectrophoresis, caused platelet aggregation and inhibited 5-HT uptake. The damaging effects of Poly-L and Poly-O were more severe and more closely related to concentration than that of PS. The negatively charged macromolecules Poly-IC and NaPS increased the anodic electrophoretic mobility. Poly-IC and heparin caused a low degree of platelet clumping and no inhibition of 5-HT uptake. NaPS produced severe platelet damage with extensive clumping and complete inhibition of 5-HT uptake. Na laurate had the same effect, but did not alter electrophoretic mobility. ADP caused concentration-dependent platelet aggregation and inhibition of 5-HT uptake. The effects of ADP and NaPS were compared in agitated and non-agitated platelet samples containing identical concentrations of the 2 compounds. Agitation was found to increase the degree of platelet clumping and to reduce 5-HT uptake.

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Investigating the influence of aromatic moieties on the formulation of hydrophobic natural products and drugs in poly(2-oxazoline) based amphiphiles

10.26434/chemrxiv.5787711.v1 ◽

2018 ◽

Author(s):

Robert Luxenhofer ◽

Michael M Lübtow ◽

Lukas Hahn ◽

Thomas Lorson ◽

Rainer Schobert

Keyword(s):

Natural Products ◽

Small Molecules ◽

Water Solubility ◽

Drug Loading ◽

High Drug ◽

Long Term Stability ◽

Aromatic Content ◽

Important Interaction ◽

Amorphous Structures ◽

High Drug Loading

Many natural compounds with interesting biomedical properties share one physicochemical property, namely a low water solubility. Polymer micelles are, among others, a popular means to solubilize hydrophobic compounds. The specific molecular interactions between the polymers and the hydrophobic drugs are diverse and recently it has been discussed that macromolecular engineering can be used to optimize drug loaded micelles. Specifically, π-π stacking between small molecules and polymers has been discussed as an important interaction that can be employed to increase drug loading and formulation stability. Here, we test this hypothesis using four different polymer amphiphiles with varying aromatic content and various natural products that also contain different relative amounts of aromatic moieties. While in the case of paclitaxel, having the lowest relative content of aromatic moieties, the drug loading decreases with increasing relative aromatic amount in the polymer, the drug loading of curcumin, having a much higher relative aromatic content, is increased. Interestingly, the loading using schizandrin A, a dibenzo[a,c]cyclooctadiene lignan with intermediate relative aromatic content is not influenced significantly by the aromatic content of the polymers employed. The very high drug loading, long term stability, the ability to form stable highly loaded binary coformulations in different drug combinations, small sized formulations and amorphous structures in all cases, corroborate earlier reports that poly(2-oxazoline) based micelles exhibit an extraordinarily high drug loading and are promising candidates for further biomedical applications. The presented results underline that the interaction between the polymers and the incorporated small molecules are complex and must be investigated in every specific case.<br>

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Surface charge and extracellular polymer of sludge in the anaerobic degradation process

Water Science & Technology ◽

10.2166/wst.1996.0565 ◽

1996 ◽

Vol 34 (5-6) ◽

pp. 309-316 ◽

Cited By ~ 20

Author(s):

X. S. Jia ◽

Herbert H. P. Fang ◽

H. Furumai

Keyword(s):

Surface Charge ◽

Growth Phase ◽

Anaerobic Degradation ◽

Degradation Process ◽

Anaerobic Sludge ◽

Batch Experiments ◽

High Substrate Concentration ◽

Negative Surface ◽

Negative Surface Charge ◽

Extracellular Polymer

Changes of surface charge and extracellular polymer (ECP) content were investigated in batch experiments for three anaerobic sludges, each of which had been enriched at 35°C and pH 639-7.3 for more than 40 batches using propionate, butyrate and glucose, individually, as the sole substrate. Results showed that both ECP and the negative surface charge were dependent on the growth phase of microorganisms. They increased at the beginning of all batches when the microorganisms were in the prolific-growth phase, having high substrate concentration and food-to-microorganisms ratio. Both later gradually returned to their initial levels when the microorganisms were in the declined-growth phase, as the substrate became depleted. The negative surface charge increased linearly with the total-ECP content in all series with slopes of 0.0187, 0.0212 and 0.0157 meq/mg-total-ECP for sludge degrading propionate, butyrate and glucose, respectively. The change of surface charge for the first two sludges was mainly due to the increase of proteinaceous fraction of ECP; but, for glucose-degrading sludge, that could be due to the increases of both proteinaceous and carbohydrate fractions of ECP. The negative-charged nature of anaerobic sludge implies that cations should be able to promote granulation of anaerobic sludge.

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Polymeric Nanoparticles for Brain Drug Delivery - A Review

Current Drug Metabolism ◽

10.2174/1389200221666200508074348 ◽

2020 ◽

Vol 21 (9) ◽

pp. 649-660

Author(s):

Subashini Raman ◽

Syed Mahmood ◽

Ayah R. Hilles ◽

Md Noushad Javed ◽

Motia Azmana ◽

...

Keyword(s):

Drug Delivery ◽

Surface Modification ◽

Polymeric Nanoparticles ◽

Drug Loading ◽

Preparation Methods ◽

Brain Drug Delivery ◽

Polymeric Nanoparticle ◽

Relationship Of ◽

The Relationship ◽

The Brain

Background: Blood-brain barrier (BBB) plays a most hindering role in drug delivery to the brain. Recent research comes out with the nanoparticles approach, is continuously working towards improving the delivery to the brain. Currently, polymeric nanoparticle is extensively involved in many therapies for spatial and temporal targeted areas delivery. Methods: We did a non-systematic review, and the literature was searched in Google, Science Direct and PubMed. An overview is provided for the formulation of polymeric nanoparticles using different methods, effect of surface modification on the nanoparticle properties with types of polymeric nanoparticles and preparation methods. An account of different nanomedicine employed with therapeutic agent to cross the BBB alone with biodistribution of the drugs. Results: We found that various types of polymeric nanoparticle systems are available and they prosper in delivering the therapeutic amount of the drug to the targeted area. The effect of physicochemical properties on nanoformulation includes change in their size, shape, elasticity, surface charge and hydrophobicity. Surface modification of polymers or nanocarriers is also vital in the formulation of nanoparticles to enhance targeting efficiency to the brain. Conclusion: More standardized methods for the preparation of nanoparticles and to assess the relationship of surface modification on drug delivery. While the preparation and its output like drug loading, particle size, and charge, permeation is always conflicted, so it requires more attention for the acceptance of nanoparticles for brain delivery.

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