Rational design of polymer-lipid nanoparticles for docetaxel delivery

Albano, Juan M. R.; Ribeiro, Lígia Nunes de Morais; Couto, Verônica Muniz; Messias, Mariana Barbosa; Silva, Gustavo Henrique Rodrigues da; Breitkreitz, Márcia Cristina; Paula, Eneida de; Pickholz, Mónica

doi:10.1016/j.colsurfb.2018.11.077

Cited by 32 publications

(15 citation statements)

References 61 publications

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“…The DTX is present in low concentrations in the NLS-DTX, and this makes it difficult to detect the bands assigned to the drug and to assess changes in the frequency of them, FTIR technique, therefore doesn't confirm the presence of the drug in the carrier. Similar results were analyzed by Albano et al [35] in a study that observed the absence of the DTX band in lipid-polymeric nanoparticle by FTIR technique. During preparation of the nanoparticles, there is a possibility of different physical-chemical interactions, such as the formation of hydrogen bonds between SLN components and drug.…”

Section: Fourier Transform Infrared and Raman Spectroscopysupporting

confidence: 87%

Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells

et al. 2020

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Background: Metastasis causes the most breast cancer-related deaths in women. Here, we investigated the antitumor effect of solid lipid nanoparticles (SLN-DTX) when used in the treatment of metastatic breast tumors using 4T1-bearing BALB/c mice. Results: Solid lipid nanoparticles (SLNs) were produced using the high-energy method. Compritol 888 ATO was selected as the lipid matrix, and Pluronic F127 and Span 80 as the surfactants to stabilize nanoparticle dispersion. The particles had high stability for at least 120 days. The SLNs' dispersion size was 128 nm, their polydispersity index (PDI) was 0.2, and they showed a negative zeta potential. SLNs had high docetaxel (DTX) entrapment efficiency (86%), 2% of drug loading and showed a controlled drug-release profile. The half-maximal inhibitory concentration (IC 50) of SLN-DTX against 4T1 cells was more than 100 times lower than that of free DTX after 24 h treatment. In the cellular uptake test, SLN-DTX was taken into the cells significantly more than free DTX. The accumulation in the G2-M phase was significantly higher in cells treated with SLN-DTX (73.7%) than in cells treated with free DTX (23.0%), which induced subsequent apoptosis. TEM analysis revealed that SLN-DTX internalization is mediated by endocytosis, and fluorescence microscopy showed DTX induced microtubule damage. In vivo studies showed that SLN-DTX compared to free docetaxel exhibited higher antitumor efficacy by reducing tumor volume (p < 0.0001) and also prevented spontaneous lung metastasis in 4T1 tumor-bearing mice. Histological studies of lungs confirmed that treatment with SLN-DTX was able to prevent tumor. IL-6 serum levels, ki-67 and BCL-2 expression were analyzed and showed a remarkably strong reduction when used in a combined treatment. Conclusions: These results indicate that DTX-loaded SLNs may be a promising carrier to treat breast cancer and in metastasis prevention.

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Section: Fourier Transform Infrared and Raman Spectroscopysupporting

confidence: 87%

Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells

et al. 2020

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“…The LC (wt%) at the drug-to-HSA ratio of 0.2 was 11.2 ± 1.4%, which is higher than those obtained via other previous fabrication approaches, such as the reported albumin-based nanoparticles of curcumin (7.2 ± 2.5%) [40], paclitaxel (7.89 ± 1.31%) [41], tacrolimus (1.5 ± 0.1%) [42] and DTX (7%) [43]. Other nanoparticles of DTX, such as chitosan-based DTX nanoparticles [25], exhibit a similar LC (8–12%) with that achieved by this current approach and the solid lipid DTX nanoparticles show a much lower LC (1.90%, 1,92%) than the approach reported herein [44]. Meanwhile, the release kinetics exhibited by the DTX-NPs demonstrated that the encapsulated drugs underwent a sustained release, suggesting that they provide an effective means or prolonging the drug in circulation in vivo.…”

Section: Discussionmentioning

confidence: 64%

Docetaxel-loaded human serum albumin (HSA) nanoparticles: synthesis, characterization, and evaluation

Sun

et al. 2019

BioMed Eng OnLine

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BackgroundDocetaxel (DTX) is an anticancer drug that is currently formulated with polysorbate 80 and ethanol (50:50, v/v) in clinical use. Unfortunately, this formulation causes hypersensitivity reactions, leading to severe side-effects, which have been primarily attributed to polysorbate 80.MethodsIn this study, a DTX-loaded human serum albumin (HSA) nanoparticle (DTX-NP) was designed to overcome the hypersensitivity reactions that are induced by polysorbate 80. The methods of preparing the DTX-NPs have been optimized based on factors including the drug-to-HSA weight ratio, the duration of HSA incubation, and the choice of using a stabilizer. Synthesized DTX-NPs were characterized with regard to their particle diameters, drug loading capacities, and drug release kinetics. The morphology of the DTX-NPs was observed via scanning electron microscopy (SEM) and the successful preparation of DTX-NPs was confirmed via differential scanning calorimetry (DSC). The cytotoxicity and cellular uptake of DTX-NPs were investigated in the non-small cell lung cancer cell line A549 and the maximum tolerated dose (MTD) of DTX-NPs was evaluated via investigations with BALB/c mice.ResultsThe study showed that the loading capacity and the encapsulation efficiency of DTX-NPs prepared under the optimal conditions was 11.2 wt% and 63.1 wt%, respectively and the mean diameter was less than 200 nm, resulting in higher permeability and controlled release. Similar cytotoxicity against A549 cells was exhibited by the DTX-NPs in comparison to DTX alone while higher maximum tolerated dose (MTD) with the DTX-NPs (75 mg/kg) than with DTX (30 mg/kg) was demonstrated in mice, suggesting that the DTX-NPs prepared with HSA yielded similar anti-tumor activity but were accompanied by less systemic toxicity than solvent formulated DTX.ConclusionsDTX-NPs warrant further investigation and are promising candidates for clinical applications.

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“…The failure of chemotherapy in lung cancer treatment is mainly due to resistance mechanisms against chemotherapeutic agents, which result in a lack of therapeutic response [3,4]. Resistance phenomenon can occur by efflux pumps as P-glycoprotein (P-gp), which is expressed in human cells and acts as a localized drug transport mechanism, actively exporting drugs out of the cell [3,5,6]. In that sense, the efflux mechanism shows great clinical importance on lung cancer treatment and several compounds with P-gp inhibitor properties have been studied [7] to modulate chemotherapy resistance and to provide a more pronounced effect to chemotherapeutic drugs.…”

Section: Introductionmentioning

confidence: 99%

Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells

et al. 2020

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Background: As part of the efforts to find natural alternatives for cancer treatment and to overcome the barriers of cellular resistance to chemotherapeutic agents, polymeric nanocapsules containing curcumin and/or methotrexate were prepared by an interfacial deposition of preformed polymer method. Methods: Physicochemical properties, drug release experiments and in vitro cytotoxicity of these nanocapsules were performed against the Calu-3 lung cancer cell line. Results: The colloidal suspensions of nanocapsules showed suitable size (287 to 325 nm), negative charge (−33 to −41 mV) and high encapsulation efficiency (82.4 to 99.4%). Spherical particles at nanoscale dimensions were observed by scanning electron microscopy. X-ray diffraction analysis indicated that nanocapsules exhibited a non-crystalline pattern with a remarkable decrease of crystalline peaks of the raw materials. Fourier-transform infrared spectra demonstrated no chemical bond between the drug(s) and polymers. Drug release experiments evidenced a controlled release pattern with no burst effect for nanocapsules containing curcumin and/or methotrexate. The nanoformulation containing curcumin and methotrexate (NCUR/MTX-2) statistically decreased the cell viability of Calu-3. The fluorescence and morphological analyses presented a predominance of early apoptosis and late apoptosis as the main death mechanisms for Calu-3. Conclusions: Curcumin and methotrexate co-loaded nanocapsules can be further used as a novel therapeutic strategy for treating non-small-cell lung cancer.

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Rational design of polymer-lipid nanoparticles for docetaxel delivery

Cited by 32 publications

References 61 publications

Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells

Docetaxel-loaded solid lipid nanoparticles prevent tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells

Docetaxel-loaded human serum albumin (HSA) nanoparticles: synthesis, characterization, and evaluation

Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells

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