Nanoparticles in drug delivery: mechanism of action, formulation and clinical application towards reduction in drug-associated nephrotoxicity

Cooper, Dustin L.; Conder, Christopher M.; Harirforoosh, Sam

doi:10.1517/17425247.2014.938046

Cited by 44 publications

(39 citation statements)

References 147 publications

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“…11,12 The advantages of NP-mediated drug delivery methods include their ability to modify the pharmacological effect, pharmacokinetics, bioavailability, bio-distribution, extended circulation time of drugs, and drug targeting to the site of action. 13,14 …”

Section: Introductionmentioning

confidence: 99%

Gemcitabine and Antisense-microRNA Co-encapsulated PLGA–PEG Polymer Nanoparticles for Hepatocellular Carcinoma Therapy

Devulapally

Foygel

Sekar

et al. 2016

ACS Appl. Mater. Interfaces

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Hepatocellular carcinoma (HCC) is highly prevalent, and the third most common cause of cancer-associated deaths worldwide. HCC tumors respond poorly to chemotherapeutic anticancer agents due to inherent and acquired drug resistance, and low drug permeability. Targeted drug delivery systems with significant improvement in therapeutic efficiency are needed for successful HCC therapy. Here, we report the results of a technique optimized for the synthesis and formulation of antisense-miRNA-21 and gemcitabine (GEM) co-encapsulated PEGylated-PLGA nanoparticles (NPs) and their in vitro therapeutic efficacy in human HCC (Hep3B and HepG2) cells. Water-in-oil-in-water (w/o/ w) double emulsion method was used to coload antisense-miRNA-21 and GEM in PEGylated-PLGA-NPs. The cellular uptake of NPs displayed time dependent increase of NPs concentration inside the cells. Cell viability analyses in HCC (Hep3B and HepG2) cells treated with antisense-miRNA-21 and GEM co-encapsulated NPs demonstrated a nanoparticle concentration dependent decrease in cell proliferation, and the maximum therapeutic efficiency was attained in cells treated with nanoparticles co-encapsulated with antisense-miRNA-21 and GEM. Flow cytometry analysis showed that control NPs and antisense-miRNA-21-loaded NPs are not cytotoxic to both HCC cell lines, whereas treatment with free GEM and GEM-loaded NPs resulted in ~9% and ~15% apoptosis, respectively. Cell cycle status analysis of both cell lines treated with free GEM or NPs loaded with GEM or antisense-miRNA-21 displayed a significant cell cycle arrest at the S-phase. Cellular pathway analysis indicated that Bcl2 expression was significantly upregulated in GEM treated cells, and as expected, PTEN expression was noticeably upregulated in cells treated with antisense-miRNA-21. In summary, we successfully synthesized PEGylated-PLGA nanoparticles co- encapsulated with antisense-miRNA-21 and GEM. These co-encapsulated nanoparticles revealed increased treatment efficacy in HCC cells, compared to cells treated with either antisense-miRNA-21- or GEM-loaded NPs at equal concentration, indicating that down-regulation of endogenous miRNA-21 function can reduce HCC cell viability and proliferation in response to GEM treatment.

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Section: Introductionmentioning

confidence: 99%

Gemcitabine and Antisense-microRNA Co-encapsulated PLGA–PEG Polymer Nanoparticles for Hepatocellular Carcinoma Therapy

Devulapally

Foygel

Sekar

et al. 2016

ACS Appl. Mater. Interfaces

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“…In light of emerging chronotherapeutic approaches, various chronoprogrammable drug delivery systems have been developed . These approaches include chronomodulating infusion pumps, controlled‐release microchip strategies, floating pulsatile systems, nanotechnology, press‐coating approaches, micro‐electrochemical systems, osmotic pressure, microchips, liposomes, thermosensitive hydrogels, micro‐ and nanocarriers, and microparticle‐based systems.…”

Section: Caveats Challenges and Insights On The Diagnosis And Theramentioning

confidence: 99%

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research‐practice gaps, challenges, and insights

Zheng

Kros

2017

Medicinal Research Reviews

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To date, five cancer treatment modalities have been defined. The three traditional modalities of cancer treatment are surgery, radiotherapy, and conventional chemotherapy, and the two modern modalities include molecularly targeted therapy (the fourth modality) and immunotherapy (the fifth modality). The cardiotoxicity associated with conventional chemotherapy and radiotherapy is well known. Similar adverse cardiac events are resurging with the fourth modality. Aside from the conventional and newer targeted agents, even the most newly developed, immune‐based therapeutic modalities of anticancer treatment (the fifth modality), e.g., immune checkpoint inhibitors and chimeric antigen receptor (CAR) T‐cell therapy, have unfortunately led to potentially lethal cardiotoxicity in patients. Cardiac complications represent unresolved and potentially life‐threatening conditions in cancer survivors, while effective clinical management remains quite challenging. As a consequence, morbidity and mortality related to cardiac complications now threaten to offset some favorable benefits of modern cancer treatments in cancer‐related survival, regardless of the oncologic prognosis. This review focuses on identifying critical research‐practice gaps, addressing real‐world challenges and pinpointing real‐time insights in general terms under the context of clinical cardiotoxicity induced by the fourth and fifth modalities of cancer treatment. The information ranges from basic science to clinical management in the field of cardio‐oncology and crosses the interface between oncology and onco‐pharmacology. The complexity of the ongoing clinical problem is addressed at different levels. A better understanding of these research‐practice gaps may advance research initiatives on the development of mechanism‐based diagnoses and treatments for the effective clinical management of cardiotoxicity.

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“…Things to consider when deciding to develop a nanoparticlebased therapeutic include manufacturing complexity, cost, toxicity, intra-batch uniformity, inter-batch variation, synthetic yield, characterization/validation techniques, scalability and shelf life/stability [9,42]. These are just a few of the critical characteristics that each class of nanoparticle must address in order to develop less expensive and more robust protocols to make clinical implementation a more accessible reality.…”

Section: General Nanoparticle Hurdlesmentioning

confidence: 99%

Emerging Therapeutic Delivery Capabilities and Challenges Utilizing Enzyme/Protein Packaged Bacterial Vesicles

et al. 2015

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Nanoparticle-based therapeutics are poised to play a critical role in treating disease. These complex multifunctional drug delivery vehicles provide for the passive and active targeted delivery of numerous small molecule, peptide and protein-derived pharmaceuticals. This article will first discuss some of the current state of the art nanoparticle classes (dendrimers, lipid-based, polymeric and inorganic), highlighting benefits/drawbacks associated with their implementation. We will then discuss an emerging class of nanoparticle therapeutics, bacterial outer membrane vesicles, that can provide many of the nanoparticle benefits while simplifying assembly. Through molecular biology techniques; outer membrane vesicle hijacking potentially allows for stringent control over nanoparticle production allowing for targeted protein packaged nanoparticles to be fully synthesized by bacteria.

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Nanoparticles in drug delivery: mechanism of action, formulation and clinical application towards reduction in drug-associated nephrotoxicity

Cited by 44 publications

References 147 publications

Gemcitabine and Antisense-microRNA Co-encapsulated PLGA–PEG Polymer Nanoparticles for Hepatocellular Carcinoma Therapy

Gemcitabine and Antisense-microRNA Co-encapsulated PLGA–PEG Polymer Nanoparticles for Hepatocellular Carcinoma Therapy

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research‐practice gaps, challenges, and insights

Emerging Therapeutic Delivery Capabilities and Challenges Utilizing Enzyme/Protein Packaged Bacterial Vesicles

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