Uptake of CDDP-containing polymeric micelles by cells using particle induced X-ray emission. (original) (raw)
Related papers
Particulate carriers such as polymeric micelles (PMs) and liposomes have been investigated to increase drug accumulation in tumors and reduce distribution to healthy tissues. In this study, we prepared PM and hybrid nanoparticles (HNPs) with poly(ethylene oxide)-block-poly(methacrylic acid) (PEO-b-PMAA) for loading cisplatin, and evaluated cisplatin release, cytotoxicity, and biodi-stribution in mice. PM composed of PEO-b-PMAA and HNPs composed of egg phosphatidylcholine (EPC)/PEO-b-PMAA at molar ratios of 50/2.8 (HNP-P5) and 50/50 (HNP-P50), respectively, were prepared by a nanoprecipitation method. The sizes of PM, HNP-P5, and HNP-P50 after inclusion of cisplatin were approximately 200, 100, and 55 nm, respectively, and their entrapment efficiencies were approximately 44%-66%. In the drug-release study, HNP-P5 and HNP-P50 showed reduced release of cisplatin compared with PM. Regarding the cytotoxic assay, HNP-P5 exhibited lower cy-totoxicity for mouse Lewis lung carcinoma (LLC) and mouse colon carcinoma Colon 26 cells than PM and HNP-P50. In terms of biodistribution, PM could significantly improve blood circulation and tumor accumulation after intravenous injection into Colon 26 tumor-bearing mice compared with free cisplatin, but HNP-P5 and HNP-P50 did not. EPC in HNPs might be destabilized in the circulation , although it could reduce release of cisplatin in in vitro experiments. This study suggested that polymeric micelles composed of PEO-b-PMAA are a better carrier for cisplatin than hybrid nano-particles composed of PEO-b-PMAA and EPC.
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↓).
Biomacromolecules, 2012
Three monomers with 1,3-dicarboxylate functional groups but varying spacer lengths were synthesized via carbon Michael addition using malonate esters and ethylene-(MAETC), butylene-(MABTC), and hexylene (MAHTC) glycol dimethacrylate, respectively. Poly[oligo-(ethylene glycol) methylether methacrylate] (POEGMEMA) was prepared in the presence of a RAFT (reversible addition−fragmentation chain transfer) agent, followed by chain extension with the prepared monomers to generate three different block copolymers (BP-E80, BP-B82, and BP-H79) with similar numbers of repeating units, but various spacer lengths as distinguishing features. Conjugation with platinum drugs created macromolecular platinum drugs resembling carboplatin. The amphiphilic natures of these Pt-containing block copolymers led to the formation micelles in solution. The rate of drug release of all micelles was similar, but a noticeable difference was the increasing stability of the micelle against dissociation with increasing spacer length. The platinum conjugated polymer showed high activity against A549, OVCAR3, and SKOV3 cancer cell lines exceeding the activity of carboplatin, but only the micelle based on the longest spacer had IC 50 values as low as cisplatin. Cellular uptake studies identified a better micelle uptake with increasing micelle stability as a possible reason for lower IC 50 values. The clonogenic assay revealed that micelles loaded with platinum drugs, in contrast to low molecular weight carboplatin, have not only better activity within the frame of a 72 h cell viability study, but also display a longer lasting effect by preventing the colony formation A549 for more than 10 days.
Intratumoral radiation therapy -'brachytherapy'is a highly effective treatment for solid tumors, particularly prostate cancer. Current titanium seed implants, however, are permanent and are limited in clinical application to indolent malignancies of low-to intermediate-risk. Attempts to develop polymeric alternatives, however, have been plagued by poor retention and off-target toxicity due to degradation. Herein, we report on a new approach whereby thermally sensitive micelles composed of an elastin-like polypeptide (ELP) are labeled with the radionuclide 131 I to form an in situ hydrogel that is stabilized by two independent mechanisms: first, body heat triggers the radioactive ELP micelles to rapidly phase transition into an insoluble, viscous coacervate in under 2 min; second, the high energy β-emissions of 131 I further stabilize the depot by introducing crosslinks within the ELP depot over 24 h. These injectable brachytherapy hydrogels were used to treat two aggressive orthotopic tumor models in athymic nude mice: a human PC-3 M-luc-C6 prostate tumor and a human BxPc3-luc2 pancreatic tumor model. The ELP depots retained greater than 52% and 70% of their radioactivity through 60 days in the prostate and pancreatic tumors with no appreciable radioactive accumulation (≤0.1% ID) in off-target tissues after 72 h. The 131 I-ELP depots achieved N 95% tumor regression in the prostate tumors (n = 8); with a median survival of more than 60 days compared to 12 days for control mice. For the pancreatic tumors, ELP brachytherapy (n = 6) induced significant growth inhibition (p = 0.001, ANOVA) and enhanced median survival to 27 days over controls.
Chemistry of Materials, 2012
Well-defined and nontoxic cross-linked polymeric micelles, containing either permanent or acid degradable cross-linkers, were employed for efficient intracellular delivery of cisplatin. The self-assembled structures were generated from triblock copolymers of poly(oligo(ethylene glycol) methylether methacrylate)-block-poly(N-hydroxysuccinic methacrylate)-block-poly(1,1-di-tert-butyl 3-(2-(methacryloyloxy)ethyl) butane-1,1,3-tricarboxylate) (POEGMEMA-b-PNHSMA-b-PMAETC) loaded with cisplatinum. The polymeric micelles were subsequently cross-linked via a reaction between pendant activated esters at the nexus core of the triblock copolymer using acid degrdabale ketal diamino cross-linkers. An in vitro study confirmed that both uncross-linked and cross-linked micelles prior to the loading of the platinum drug were nontoxic against OVCAR-3 cells even at high polymer concentration (around 300 μg mL −1). The drug loaded cross-linked platinum polymeric micelles were superior to the uncross-linked platinum polymeric micelles in terms of cytotoxicity against OVCAR-3, due to a higher cellular uptake. Although there was no significant difference in cytotoxicity of cross-linked platinum polymeric micelles using different cross-linkers (permanent and acid cleavable) after 72 h of exposure, the difference was noticeable after 24 h of incubation, highlighting a much higher activity for acid degradable crosslinked micelles with conjugated platinum drugs. Moreover, the clonogenic assay suggested that cross-linked micelle loaded platinum drugs, in contrast to uncross-linked micelles, can effectively inhibit the OVCAR-3 cell regrowth for an extended period of time (10 days), even at very low micellar concentrations. In summary, acid degradable linkers ensure high cellular uptake compared to uncross-linked micelles but also lead to a faster drug action in comparison to a permanently cross-linked micelle.
Anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on LNCaP prostate cancer cells
European Journal of Pharmaceutics and Biopharmaceutics, 2007
The in vitro anticancer activity of cisplatin-loaded PLGA-mPEG nanoparticles on human prostate cancer LNCaP cells was investigated. The uptake of the PLGA-mPEG nanoparticles by the LNCaP cells was also studied. Blank PLGA-mPEG nanoparticles exhibited low cytotoxicity, which increased with increasing PLGA/PEG ratio in the PLGA-mPEG copolymer used to prepare the nanoparticles, possibly due to the increased cell uptake observed with increasing PLGA/PEG ratio. PLGA-mPEG nanoparticles loaded with cisplatin exerted in vitro anticancer activity against LNCaP cells that was comparable to the activity of free (non-entrapped in nanoparticles) cisplatin. Little differences in the in vitro anticancer activity of the different nanoparticle compositions were found, which may result from the differences observed between the different nanoparticles compositions in the uptake by the LNCaP cells and in the leakage of cisplatin from the nanoparticles during incubation with the cells. Visual evidence of nanoparticles' uptake by the LNCaP cells was obtained with nanoparticles labeled with PLGA(4165)-PyrBu(274) or dextran-rhodamine B isothiocyanate using fluorescence microscopy. Moreover, in some cases fluorescence around or inside cell nuclei was observed, which, if verified by further studies, would indicate that PLGA-PEG nanoparticles might prove to be useful in site-specific delivery of drugs whose site of pharmacological activity is cell nucleus.
Cisplatin (cis-diaminodichloroplatinum, CDDP) loaded methoxy poly (ethylene glycol)-block-poly (glutamic acid-co-phenyl alanine) [mPEG-b-P (Glu 10 -co-Phe 10 ) (PGlu 10 ) and mPEG-b-P (Glu 20 -co-Phe 10 ) (PGlu 20 )] nanoparticles with two different formulations (CDDP/PGlu 10 and CDDP/PGlu 20 ) are successfully developed in uniformly sizes. In 190 h, the CDDP/PGlu 10 shows 30% release at physiological pH and 39% at lysosomal pH. Similarly, the CDDP/PGlu 20 shows 60% release at physiological pH and 90% release at lysosomal pH. The sustained and controlled release of both formulations evidences the in vitro longevity of the nanoparticles. The cell proliferation inhibition of nanoparticles against human breast cancer cell line ZR-75-30 is dose and time dependent. Both CDDP/PGlu 10 and CDDP/PGlu 20 show excellent hemo compatibility as evaluated by hemolysis experiments. The in vivo fate of CDDP and CDDP loaded nanoparticles are evaluated by pharmacokinetics studies. Free CDDP underwgoes instant platinum concentration decrease after intravenous administration with 1.0 wt% left in 24 h while the CDDP loaded nanoparticles show prolonged blood circulation time with 5 wt% (CDDP/PGlu 20 ) to 14 wt% (CDDP/PGlu 10 ) left in 24 h. This prolonged blood circulation of CDDP loaded nanoparticles makes them as promising nanocarriers for tumor targeting delivery.
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.
The purpose of present work was to prepare optimized novel Cisplatin loaded polymeric micelles administered via inhalational route through Dry Powder Inhaler for the treatment of Non-Small Cell of Lung Cancer. Cisplatin loaded micelles were prepared incorporating Pluronic F-127 using rotary vacuum evaporation, spray drying and ultrasonic homogenization technique. The critical process as well as product related parameters identified and screened by Plackett and Burman Design and further optimized by 3 2 factorial design. Prepared batches were evaluated for morphology, particle size, entrapment efficiency, drug loading, in-vitro diffusion study and aerodynamic behavior. Aspiration rate and Polymer concentration were identified as critical variables using Plackett and Burman design. Then, 3 2 full factorial design was selected for optimization of Polymeric micelles using Aspiration rate and Polymer concentration as independent variable and % Encapsulation efficiency and micelle size as dependent variable.3 2 factorial design suggested optimized parameters as Aspirator capacity-42.51 and Polymer concentration-103.98 mg. The average micelle size of the optimized batch was found to be 264 nm with an entrapment efficiency of 89%. Micelles were found to be uniform spherical shape and size was less than 5μm on the basis of Zeta sizer and Transmission Electron Microscopy study.