Novel Hydrophilic Drug Polymer Nano-Conjugates of Cisplatin Showing Long Blood Retention Profile - Its Release Kinetics, Cellular Uptake and Bio-Distribution (original) (raw)
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Journal of Nanobiotechnology
Background Nowadays, nanoparticles (NPs) have evolved as multifunctional systems combining different custom anchorages which opens a wide range of applications in biomedical research. Thus, their pharmacological involvements require more comprehensive analysis and novel nanodrugs should be characterized by both chemically and biological point of view. Within the wide variety of biocompatible nanosystems, iron oxide nanoparticles (IONPs) present mostly of the required features which make them suitable for multifunctional NPs with many biopharmaceutical applications. Results Cisplatin-IONPs and different functionalization stages have been broadly evaluated. The potential application of these nanodrugs in onco-therapies has been assessed by studying in vitro biocompatibility (interactions with environment) by proteomics characterization the determination of protein corona in different proximal fluids (human plasma, rabbit plasma and fetal bovine serum),. Moreover, protein labeling and ...
Star-shaped nano-conjugates of cisplatin with high drug payload
International Journal of Pharmaceutics, 2011
Core-shell type star polymer bearing carboxylate functions was designed and evaluated as nanocarrier of cisplatin. The synthetic route to the star macromolecules involved the "core first" method to yield a precursor star polymer with a highly branched poly(styrene) core and poly(tert-butyl acrylate) arms. Two polymers derived from a common core of M n = 2400 g/mol and degrees of polymerization of the linear arms 38 and 58 were subjected to acidic hydrolysis to obtain stars with a hydrophilic and multifunctional shell. Diffusion ordered NMR spectroscopic study revealed that the two products presented single populations of stars with values of the apparent hydrodynamic radii 12.9 nm and 14.0 nm, respectively. The stars were loaded with cisplatin via ligand exchange reaction achieving remarkable high drug payload of 45% (w/w). The conjugates were stable in an aqueous solution exhibiting no precipitation for a prolonged period of time. The release profile of the platinum (II) complexes in phosphate buffered saline and RPMI-1640 liquid medium at 37 • C indicated sustained manner of drug release with no initial burst effect. In vitro cell viability study, using four human tumor cell lines proved that the conjugates exhibited lower cytotoxicity compared to the free agent. The established cellular accumulation of cisplatin indicated uptake of the nanoconjugates by the cells through endocytosis.
Journal of Controlled Release, 2002
The in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties of PLGA-mPEG nanoparticles of cisplatin were investigated. The nanoparticles were prepared by a double emulsion method and characterized with regard to their morphology, size, zeta potential and drug loading. The rate of in vitro degradation of the PLGA-mPEG nanoparticles in PBS (pH 7.4) depended on their composition, increasing when the mPEG content (mPEG:PLGA ratio) of the nanoparticles increased. Sustained cisplatin release over several hours from the PLGA-mPEG nanoparticles in vitro (PBS) was observed. The composition of the nanoparticles affected drug release: the rate of release increased when the mPEG content of the nanoparticles increased. Within the range of drug loadings investigated, the drug loading of the nanoparticles did not have any significant effect on drug release. The loading efficiency was low and needs improvement in order to obtain PLGA-mPEG nanoparticles with a satisfactory cisplatin content for therapeutic application. The i.v. administration of PLGA-mPEG nanoparticles of cisplatin in BALB / c mice resulted in prolonged cisplatin residence in systemic blood circulation. The results appear to justify further investigation of the suitability of the PLGA-mPEG nanoparticles for the controlled i.v. delivery and / or targeting of cisplatin.
In-vivo evaluation of cisplatin nanoparticles encompass natural polymer
International Journal of Pharmaceutical Research and Life Sciences, 2020
Cancer is assemblage diseases involving abnormal cell growth amid the potential of spread to other parts of the body due to tobacco use are the cause of about of cancer deaths. Another 10% is due to obesity, poor diet & drinking alcohol. In 2012 about 14.1 million new cases of cancer occurred globally. In females, the most common type is breast cancer. Cisplatin also known as cytophosphane is a nitrogen mustard alkylating agent from the oxazophosphinans groups were used to treat cancers & autoimmune disorders. Based on the above reasons I will fix the aim Preparation characterization of Cisplatin- nano particles & its anticancer activity. Solid tumor volume examination report showed that the assessment of different day indication 15,20,25 & 30th variations of different groups of tumor volumes were decreased CPG Nanoparticles (100 mg/kg)+ DAL(15th day 4.97±0.24↓), (20th day 0.6±0.13↓), (25th day 1.35±0.30↓) & (30th day 1.89±0.13↓).
Polymer-based delivery vehicle for cisplatin
TechConnect Briefs, 2011
Cisplatin is one of the most widely used agents in the treatment of a variety of tumors, but dose-limiting toxicities or intrinsic and acquired resistance limit its application. We report an unique strategy to deliver cisplatin to melanoma cells by sandwiching the drug between two oppositely charged polyelectrolytes: chitosan (CH) and carboxymethylcellulose (CMC), yielding cationic nanoparticles that present optimal colloid stability. Moreover, the relevance of CH structure was investigated by testing two CH with different degrees of acetylation of the glucosamine monomer. Both CH formed colloidal particles with similar sizes when mixed with CMC. However, only the CH with higher charge densities formed stable complexes with CMC to efficiently deliver the drug into cells. The cytostatic effects of free and encapsulated drug towards melanoma cells, were estimated by using the XTT assay. The results show that the chemotherapeutic drug is very cytotoxic in melanoma cells. The effectiveness of encapsulated drug against melanoma cells is approximately one order of magnitude greater than that of free drug. The strategy of delivering CisPt to melanoma cancer cells opens up avenues for systemic targeted therapy against this type of cancer using platinum drugs. More broadly, by targeting tumor-specific antigens, using similarly engineered nanoparticles, it may be possible to selectively deliver a therapeutic dose of platinum drugs to a myriad of cancers. Further studies with relevant animal models are needed.
Cisplatin and Nano-particle Formulations of Cisplatin for Cancer Therapy: A Review
Journal of Pharmaceutical Research International
Cisplatin (cis-(diammine)dichloridoplatinum(II)) is the first platinum-based compound approved by the United States Food and Drug Administration (FDA) (U.S.). This is a first-line chemotherapeutic treatment used alone or combined with other anticancer drugs to treat a broad spectrum of malignancies, with cisplatin-based nano-formulations currently in clinical studies. Cisplatin has several drawbacks, including low aqueous solubility, drug resistance, and toxicity, all of which can be addressed by encapsulating the drug in Nemours nanocarriers. The various nano-delivery technologies developed for Cisplatin are covered in vast literature from different electronic databases. This review focuses on comparative findings over the recent advancements, developments, innovations, and updated literature for various CDDP nano-carrier systems.
Cisplatin-incorporated nanoparticles of poly(acrylic acid-co-methyl methacrylate) copolymer
International Journal of Nanomedicine, 2013
Background: Although cisplatin is extensively used in the clinical field, its intrinsic toxicity limits its clinical use. We investigated nanoparticle formations of poly(acrylic acid-co-methyl methacrylate) (PAA-MMA) incorporating cisplatin and their antitumor activity in vitro and in vivo. Methods: Cisplatin-incorporated nanoparticles were prepared through the ion-complex formation between acrylic acid and cisplatin. The anticancer activity of cisplatin-incorporated nanoparticles was assessed with CT26 colorectal carcinoma cells. Results: Cisplatin-incorporated nanoparticles have small particle sizes of less than 200 nm with spherical shapes. Drug content was increased according to the increase of the feeding amount of cisplatin and acrylic acid content in the copolymer. The higher acrylic acid content in the copolymer induced increase of particle size and decrease of zeta potential. Cisplatin-incorporated nanoparticles showed a similar growth-inhibitory effect against CT26 tumor cells in vitro. However, cisplatin-incorporated nanoparticles showed improved antitumor activity against an animal tumor xenograft model. Conclusion: We suggest that PAA-MMA nanoparticles incorporating cisplatin are promising carriers for an antitumor drug-delivery system.
Artificial Cells, Nanomedicine, and Biotechnology, 2019
Cisplatin cis-(diammine)dichloridoplatinum(II) (CDDP) is the first platinum-based complex approved by the food and drug administration (FDA) of the United States (US). Cisplatin is the first line chemotherapeutic agent used alone or combined with radiations or other anti-cancer agents for a broad range of cancers such as lung, head and neck. Aroplatin TM , Lipoplatin TM and SPI-077 are PEGylated liposomebased nano-formulations that are still under clinical trials. They have many limitations, for example, poor aqueous solubility, drug resistance and toxicities, which can be overcome by encapsulating the cisplatin in Nemours nanocarriers. The extensive literature from different electronic databases covers the different nano-delivery systems that are developed for cisplatin. This review critically emphasizes on the recent advancement, development, innovations and updated literature reported for different carrier systems for CDDP.
Polymer Journal
Stabilized polymeric aggregates (SPAs) comprising poly(acrylic acid) chains were studied as a delivery platform for cisplatin. SPAs were prepared by blending a poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) triblock copolymer with a poly(acrylic acid)-block-poly(propylene oxide)-block-poly(acrylic acid) triblock copolymer and additional loading and photocrosslinking of pentaerythritol tetraacrylate. Dynamic light scattering analysis revealed particles with a hydrodynamic diameter of 176 nm and a monomodal particle size distribution. The stabilized polymeric aggregates were loaded with cisplatin by a ligand exchange reaction, achieving a high loading efficiency of 76%. A study on the release of complexes of platinum(II) from the particles in phosphate-buffered saline (PBS) and citrate buffer solution (CBS) at 37°C revealed a sustained release profile. More than 90% and nearly 80% of the loaded drug were released within 312 h in PBS and CBS, respectively. The in vitro cell viability assay indicated that cisplatin immobilized in the SPAs is less cytotoxic than the non-immobilized agent. The intracellular accumulation of the entrapped complex was comparable to that of the free drug.
Rationally engineered polymeric cisplatin nanoparticles for improved antitumor efficacy
Nanotechnology, 2011
The use of cisplatin, a first line chemotherapy for most cancers, is dose-limited due to nephrotoxicity. While this toxicity can be addressed through nanotechnology, previous attempts at engineering cisplatin nanoparticles have been limited by the impact on the potency of cisplatin. Here we report the rational engineering of a novel cisplatin nanoparticle by harnessing a novel polyethylene glycol-functionalized poly-isobutylene-maleic acid (PEG-PIMA) copolymer, which can complex with cis-platinum (II) through a monocarboxylato and a coordinate bond. We show that this complex self-assembles into a nanoparticle, and exhibits an IC50 = 0.77 ± 0.11 µM comparable to that of free cisplatin (IC50 = 0.44 ± 0.09 µM). The nanoparticles are internalized into the endolysosomal compartment of cancer cells, and release cisplatin in a pH-dependent manner. Furthermore, the nanoparticles exhibit significantly improved antitumor efficacy in a 4T1 breast cancer model in vivo, with limited nephrotoxicity, which can be explained by preferential biodistribution in the tumor with reduced kidney concentrations. Our results suggest that the PEG-PIMA-cisplatin nanoparticle can emerge as an attractive solution to the challenges in cisplatin chemotherapy.