Polyethylene sebacate doxorubicin nanoparticles: role of carbohydrate anchoring on <i>in vitro</i> and <i>in vivo</i> anticancer efficacy

Pranatharthiharan, Sandhya; Patel, Mitesh D.; Malshe, V. C.; Devarajan, Padma V.

doi:10.3109/10717544.2015.1135488

Cited by 9 publications

(3 citation statements)

References 53 publications

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“…This could be attributed to the PDA coating was partially hydrolyzed and detached from the surface of MSNs in the acidic condition. Furthermore, the solubility of DOX is dramatically enhanced at low pH, which may also contribute to rapid release in mildly acidic buffers (Pranatharthiharan et al, 2016 ). In a word, PDA, as an outstanding gatekeeper, effectively encapsulated drug inside MSNs and prevented burst release from the pore channels.…”

Section: Resultsmentioning

confidence: 99%

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy

Wei

Gao

Wang³

et al. 2017

Drug Delivery

137

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We reported a simple polydopamine (PDA)-based surface modification method to prepare novel targeted doxorubicin-loaded mesoporous silica nanoparticles and peptide CSNRDARRC conjugation (DOX-loaded MSNs@PDA-PEP) for enhancing the therapeutic effects on bladder cancer. Drug-loaded NPs were characterized in terms of size, size distribution, zeta potential, transmission electron microscopy (TEM), Brunauer-Emmett-Teller (BET) surface area and drug loading content. In vitro drug release indicated that DOX-loaded MSNs@PDA and MSNs@PDA-PEP had similar release kinetic profiles of DOX. The PDA coating well controlled DOX release and was highly sensitive to pH value. Confocal laser scanning microscopy (CLSM) showed that drug-loaded MSNs could be internalized by human bladder cancer cell line HT-1376, and DOX-loaded MSNs@PDA-PEP had the highest cellular uptake efficiency due to ligand-receptor recognition. The antitumor effects of DOX-loaded nanoparticles were evaluated by the MTT assay in vitro and by a xenograft tumor model in vivo, demonstrating that targeted nanocarriers DOX-loaded MSNs@PDA-PEP were significantly superior to free DOX and DOX-loaded MSNs@PDA. The novel DOX-loaded MSNs@PDA-PEP, which specifically recognized HT-1376 cells, can be used as a potential targeted drug delivery system for bladder cancer therapy.

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Section: Resultsmentioning

confidence: 99%

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy

Wei

Gao

Wang³

et al. 2017

Drug Delivery

137

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“…In clinical practices, doxorubicin (DOX), also known as adriamycin (ADM) is a widely used treatment strategy for solid tumors, particularly cervical cancer (Zhong et al., 2017a ). DOX takes effect by affecting the activity of topoisomerase II and inhibiting the synthesis of DNA to suppress cell growth (both normal and cancer cells) (Czeczuga-Semeniuk et al., 2004 ; Pranatharthiharan et al., 2016 ). Therefore, the serious side effects of DOX, such as myelotoxicity and cumulative cardiotoxicity, limited its therapeutic indexes (Singal et al., 1987 ; Crider et al., 2012 ).…”

Section: Introductionmentioning

confidence: 99%

Surface modification of doxorubicin-loaded nanoparticles based on polydopamine with pH-sensitive property for tumor targeting therapy

Zhao

et al. 2018

Drug Delivery

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One major challenge of current surface modification of nanoparticles is the demand for chemical reactive polymeric layers, such modification is always complicated, inefficient, and may lead the polymer lose the ability to encapsulate drug. To overcome this limitation, we adopted a pH-sensitive platform using polydopamine (PDA) as a way of functionalizing nanoparticles (NPs) surfaces. All this method needed to be just a brief incubation in weak alkaline solution of dopamine, which was simple and applicable to a variety of polymer carriers regardless of their chemical reactivity. We successfully conjugated the doxorubicin (DOX)-PDA-poly (lactic-co-glycolic acid) (PLGA) NPs with two typical surface modifiers: folate (FA) and a peptide (Arg-Gly-Asp, RGD). The DOX-PDA-FA-NPs and DOX-PDA-RGD-NPs (targeting nanoparticles) were characterized by particle size, zeta potential, and surface morphology. They were quite stable in various physiological solutions and exhibited pH-sensitive property in drug release. Compared to DOX-NPs, the targeting nanoparticles possessed an excellent targeting ability against HeLa cells. In addition, the in vivo study demonstrated that targeting nanoparticles achieved a tumor inhibition rate over 70%, meanwhile prominently decreased the side effects of DOX and improve drug distribution in tumors. Our studies indicated that the DOX-PLGA-NPs modified with PDA and various functional ligands are promising nanocarriers for targeting tumor therapy.

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“…Erythrocyte Toxicity (Hemolysis Assay). The hemolysis assay was performed, following a previously reported procedure 21,22 with minor modifications. Anticoagulant treated whole blood was centrifuged at 1008g for 15 min at 4 °C.…”

Section: Methodsmentioning

confidence: 99%

Enhancing Safety and Efficacy by Altering the Toxic Aggregated State of Amphotericin B in Lipidic Nanoformulations

Das

Devarajan

2020

Mol. Pharmaceutics

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The toxicity of Amphotericin B (AmB) is contributed by the small, water-soluble aggregates of the drug. Hence, AmB lipid polymer hybrid nanoparticles (LIPOMER), comprising stearate lipids with a hydrophilic polymer Gantrez (GZ), and solid lipid nanoparticles (SLN), comprising only stearates, were prepared with the objective of monomerizing AmB. While intercalation of stearates with the hydrophobic polyene chain could hinder AmB–AmB interactions, enabling monomerization, it was hypothesized that GZ could aid in the stabilization of the monomers through hydrophilic interactions. AmB LIPOMERs and SLNs, prepared by nanoprecipitation, exhibited an average size of 350–500 nm with negative ζ potential. Polyglyceryl-6-distearate (PGDS) SLN exhibited maximum monomerization, with the highest peak IV (410 nm) to peak I (350 nm) ratio in the UV–visible spectrum. In total contrast, LIPOMERs and GZ nanoparticles revealed a hypsochromic shifted peak I between 321 and 324 nm, indicative of AmB super-aggregate formation. Super-aggregates, which result due to condensation of multiple aggregates with monomers, were attributed to extensive GZ–AmB and GZ–GZ interactions and could provide advantages of enhanced thermodynamic stability, with safety and efficacy similar to the monomeric form. Safety was confirmed by low and comparable erythrocyte toxicity exhibited by the LIPOMERs and SLNs. An in vitro efficacy study of PGDS LIPOMER and SLN against intracellular amastigotes revealed significantly lower IC50 values, which translated to a 7.1- and 6.1-fold enhancement in efficacy compared to commercial nanoformulations Amfocare (micellar AmB) and 1.79- and 1.54-fold enhancement in efficacy compared to Fungisome (liposomal AmB). High efficacy coupled with a higher selectivity index indicated the superiority of the developed AmB nanoformulations and substantiated that altering the toxic aggregated state of AmB can offer a promising approach for the design of safe and efficacious AmB lipidic nanoformulations.

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Polyethylene sebacate doxorubicin nanoparticles: role of carbohydrate anchoring on in vitro and in vivo anticancer efficacy

Cited by 9 publications

References 53 publications

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy

Polydopamine and peptide decorated doxorubicin-loaded mesoporous silica nanoparticles as a targeted drug delivery system for bladder cancer therapy

Surface modification of doxorubicin-loaded nanoparticles based on polydopamine with pH-sensitive property for tumor targeting therapy

Enhancing Safety and Efficacy by Altering the Toxic Aggregated State of Amphotericin B in Lipidic Nanoformulations

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