Here we report the design, synthesis and biological evaluation of surface-modified silica nanoparticles (SNP) for the delivery of camptothecin (CPT). Drug has been covalently linked to the nanoparticle through an ester bond with the 20-hydroxy moiety, in order to stabilize its lactone ring and to avoid unspecific release of the drug. The obtained material is highly stable in plasma, with low release of the cargo at physiological pH. Cell internalization and in vitro efficacy assays demonstrated that nanoparticles carrying CPT (SNP-CPT) entered cells via endocytosis and the intracellular release of the cargo induced cell death with half maximal inhibitory concentration (IC₅₀) values and cell cycle distribution profiles similar to those observed for the naked drug. Further, in vivo biodistribution, therapeutic efficacy and biocompatibility of the SNP-CPT were evaluated in human colorectal cancer xenografts using in vivo fluorescence or bioluminescence optical imaging. In vivo tumor-accumulation and whole-body tissue distribution were carried out based on the acquisition of fluorescence emission of a fluorophore (Cy5.5) conjugated to the SNP-CPT, as well as by HPLC quantification of tissue CPT levels. The results showed that, although SNP-CPT tended to accumulate in organs of the reticulo-endothelial system, nanoparticles boost CPT concentration in tumor vs administration of the free drug. Accordingly, SNP-CPT treatment delayed the growth of subcutaneous tumors while significantly reducing the systemic toxicity associated with CPT administration. These results indicate that the SNP-CPT could be used as a robust drug delivery system for antitumoral treatments based on CPT.
"At 24 h after injection of NP-DY682- mTHPC and NP-DY682-mTHPC-RGD, a signal was also detected in the liver. This means that, after injection, the nanoparticles were removed from the blood by cells of the mononuclear phagocyte system   and transported into the liver and, to a lesser extent, into the spleen. Taken together, this biodistribution pattern implies that tumors in the liver or lung cannot be detected by our nanoparticles , but other tumors, like superficial tumors or head and neck tumors, represent a good target. "
"To declare the in vivo releasing character of this novel 5-FU-NPs, pharmacokinetics experiments were practiced in vivo. The drugs encapsulated by NPs, a new type of medical carrier, are usually taken in by liver and spleen firstly,which contains abundant endothelial system –. According to the study in mice, we found that there exists a kind of disharmonious compartment model between different individual data and blood drug level. "
[Show abstract][Hide abstract] ABSTRACT: Background
5-Fluorouracil (5-FU) is one of the most classic chemotherapy drugs. Nanoparticle drug delivery vehicles offer superiority over target effect enhancement and abatement of side effects. Little is known however as to the specific effect of nanoparticle on peritoneal dissemination of colon cancer. The aim of this study is to prepare one NPs (nanoparticles) loaded with 5-FU and investigate the characteristic of NPs and the role of it in peritoneal metastasis nodules formation of human colon cancer.
Prepared the NPs (nanoparticles) loaded with 5-FU (5-Fluorouracil) by PEG-PLGA with the method of double emulsion. Then evaluate the characteristics of the NPs by scanning electron microscopy, analyzing the particle diameter distribution and determining the loading efficiency. Detect the release features of NPs in vitro and in vivo. Nude mice with peritoneal metastases were treated with 5-FU solution or 5-FU-NPs through peritoneal cavity. Count the nodules on peritoneum and mesenterium and survey the size of them. We got NPs with average-diameter of 310 nm. In vitro release test shows NPs can release equably for 5 days with release rate of 99.2%. In vivo, NPs group can keep higher plasma concentration of 5-FU longer than it in solution group. The number of peritoneal dissemination nodule below 1 mm in 5-FU-sol group(17.3±3.5) and 5-FU-NP group(15.2±3.2) is less than control group(27.2±4.7)(P<0.05). The total number of nodules in 5-FU-NP group(28.7±4.2) is significantly smaller than in 5-FU-sol group(37.7±6.3) (P<0.05).
The novel anti-tumor nanoparticles loaded with 5-FU by PEG-PLGA can release maintain 5 days and have inhibitory action to peritoneal dissemination of colon cancer in mice.
PLoS ONE 06/2014; 9(6):e98455. DOI:10.1371/journal.pone.0098455 · 3.23 Impact Factor
"Other alternatives for enhancing the therapeutic efficacy of CPT involve its conjugation onto various polymeric carriers which improved solubility, stability of its lactone form and reduced renal clearance (Tong & Cheng, 2010). Other alternatives include PEGylated polymers, liposomal particles, mesoporous silica nanoparticles or albumin-based nanoparticles (Schmid et al., 2007; Botella et al., 2011). Of these alternatives encapsulation within solid lipid nanoparticles (SLN) has been shown to increase in vivo stability and water solubility in CPT, improving the therapeutic of the drug. "
[Show abstract][Hide abstract] ABSTRACT: Abstract Camptothecin (CPT) and its analogs exhibit remarkable anti-tumor activity, due to their ability to inhibit DNA topoisomerase I. However, its use is limited by the lack of solubility and stability of the active lactone form. An attractive alternative is the encapsulation of CPT within liposomes. In this study, CPT was incorporated into solid lipid nanoparticles (SLN) based on the triglyceride, Compritol 888 ATO, using supercritical fluid technology without requiring the use of harmful solvents. This drug delivery system was characterized and its cytotoxicity effect was evaluated by measuring MCF7 and MCF10A cell viability as a function of drug loading during a 48-h treatment. Results showed that after 10 h of treatment, MCF7 cells displayed an IC50 of 0.23 ± 0.034 μM at a 1:5 (CPT:SLN) loading and 0.22 ± 0.027 μM at a 1:10 loading, whereas MCF10A cells displayed an IC50 of 0.40 ± 0.036 μM at 1:5 and 0.60 ± 0.063 μM at 1:10. On the other hand, the IC50 of free CPT was 0.57 ± 0.035 μM and 1.07 ± 0.077 μM for MCF7 and MCF10A cells, respectively. Cellular uptake and retention measurements in both cells displayed a two-fold increase when using the SLN formulation. The results from this study showed that the cytotoxic effects of CPT in a SLN formulation improved when compared with those seen with free CPT. The results of this study showed that delivery of CPT as a SLN formulation could be a promising strategy for enhancing its chemotherapeutic effects.
Drug Delivery 09/2013; 20(8). DOI:10.3109/10717544.2013.834412 · 2.56 Impact Factor
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