Exploration of Docetaxel Palmitate and its Solid Lipid Nanoparticles as a Novel Option for Alleviating the Rising Concern of Multi-Drug Resistance

Publication date: Available online 27 January 2020Source: International Journal of PharmaceuticsAuthor(s): Lokesh Kaushik, Shubham Srivastava, Anshul Panjeta, Dasharath Chaudhari, Rohan Ghadi, Kaushik Kuche, Ruchi Malik, Simran Preet, Sanyog Jain, Kaisar RazaAbstractDocetaxel (DTX), a widely prescribed anticancer agent, is now associated with increased instances of multidrug resistance. Also, being a problematic BCS class IV drug, it poses challenges for the formulators. Henceforth, it was envisioned to synthesize an analogue of DTX with a biocompatible lipid, i.e., palmitic acid. The in-silico studies (molecular docking and simulation) inferred lesser binding of docetaxel palmitate (DTX-PL) with P-gp vis-à-vis DTX and paclitaxel, indicating it to be a poor substrate for P-gp efflux. Solid lipid nanoparticles (SLNs) of the conjugate were prepared using various lipids, viz. palmitic acid, stearic acid, cetyl palmitate and glyceryl monostearate. The characterization studies for the nanocarrier were performed for the surface charge, drug payload, micromeritics, release pattern of drug and surface morphology. From the cytotoxicity assays on resistant MCF-7 cells, it was established that the new analogue offered substantially decreased IC50 to that of DTX. Further, apoptosis assay also corroborated the results obtained in IC50 determination wherein, SA-SLNs showed the highest apoptotic index than free DTX. The conjugate not only enhanced the solubility but also offered lowe...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research

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In conclusion, both SILA-409 and SILA-421 were demonstrated to be effective MDR reversal agents in resistant human colon cancer cells.
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
Abstract Limited by multidrug resistance (MDR) and nonspecific selectivity, free molecular chemotherapies still are inefficient in clinical cancer treatment. Nanoscale therapeutics delivery systems with controllable release capacity have been developed to reverse multidrug resistance and improve anticancer efficacy. Herein, we constructed acid-sensitive dextrin-based nanoplatforms (THDP) to deliver chemotherapies via supramolecular coordination between tetra sodium meso-tetra (sulfonatophenyl)-porphyrin zinc (II) (Zn-TPPS) and histidine modified dextrin-graft-poly (ethylene glycol) (HDP) to reverse multidrug resis...
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Tags: Int J Biol Macromol Source Type: research
In conclusion, our results confirm that Y-320 is a promising chemotherapy sensitizer for the first time. The co-administration of Y-320 and chemotherapeutic agents might be an effective and low-toxicity chemotherapeutic regime for the MDR tumor patients. PMID: 32194903 [PubMed]
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
CONCLUSIONS: This finding indicates that c-Rel, RelA and NF-κB1 subunits are responsible for the resistance of HL-60/5FU cells to 5-FU and that U-332 is able to reverse this resistance. U-332 can be viewed as an important lead compound in the search for novel drug candidates that would not cause multidrug resistance in cancer cells. PMID: 32122395 [PubMed - in process]
Source: BMC Pharmacology and Toxicology - Category: Drugs & Pharmacology Tags: BMC Pharmacol Toxicol Source Type: research
This study aimed to evaluate the anti-cancer effects of ginsenoside Rp1, actinomycin D (ActD), and their co-administration in drug-resistant cells and murine xenograft model of colon cancer, and explore the underlying mechanisms. ActD increased expression and activity of SIRT1 in drug-resistant LS513 colon cancer, OVCAR8-DXR ovarian cancer, and A549-DXR lung cancer cells, but not in ActD-sensitive SW620 colon cancer cells. Inhibition of SIRT1, either pharmacologically, with EX527 or through siRNA, stimulated p53 acetylation and apoptosis in LS513 cells when treated with ActD. ActD also increased AKT activation in drug-resi...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Development of multidrug resistance (MDR) still remains a major obstacle to the long-term success of cancer therapy. P-glycoprotein (P-gp) is a well-identified membrane transporter with capability to efflux drug molecules out of the cancer cell leading to reduced efficiency of chemotherapy. Cancer cells upregulate P-gp expression as an adaptive response to evade chemotherapy mediated cell death. While several P-gp inhibitors have been discovered by in silico and pre-clinical studies, very few have successfully passed all phases of the clinical trials. Studies show that application of P-gp inhibitors in cancer therapy regim...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: Together, we demonstrated that circRNA_103762 is upregulated in NSCLC and functions as an oncogene in NSCLC, and circRNA_103762 enhanced MDR by inhibited CHOP expression in NSCLC cells. These results will help us understand the MDR of NSCLC, providing better effective therapy strategies for patients. PMID: 32118311 [PubMed - as supplied by publisher]
Source: Clinical Lung Cancer - Category: Cancer & Oncology Authors: Tags: J Clin Lab Anal Source Type: research
Authors: Feng Z, Chen Q Abstract Acute myeloid leukemia is a common hematological malignancy that often exhibits strong drug resistance when treated using conventional chemotherapy. Although numerous studies have been carried out to develop methods of overcoming drug resistance, the results have generally been unsatisfactory. CD40 ligand (CD40L) has been shown to improve the sensitivity of cancer cells to drug treatment. In the present study, Adriamycin (ADM)-resistant human monocytic THP-1 cells (THP-1/A cells) were developed by incubating THP-1 cells with increasing concentrations of ADM. Cells were transfected w...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
In this study, we explore whether NVP-TAE684, a novel ALK inhibitor which has the potential to inhibit the function of ABC transport, could reverse ABC transporter-mediated MDR. MTT assay was carried out to determine cell viability and reversal effect of NVP-TAE684 in parental and drug resistant cells. Drug accumulation and efflux assay was performed to examine the effect of NVP-TAE684 on the cellular accumulation and efflux of chemotherapeutic drugs. The ATPase activity of ABCG2 transporter in the presence or absence of NVP-TAE684 was conducted to determine the impact of NVP-TAE684 on ATP hydrolysis. Western blot analysis...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 19 February 2020Source: Molecular and Cellular EndocrinologyAuthor(s): Tenghua Yu, Hong Cheng, Zhijuan Ding, Zhiliang Wang, Lixia Zhou, Peng Zhao, Shengxing Tan, Xue Xu, Xianming Huang, Manran Liu, Meixi Peng, Yu-an QiuAbstractRescue chemotherapy is usually the preferred treatment for patients with advanced estrogen receptor-positive (ER+) breast cancer with endocrinotherapy resistance. However, these patients often simultaneously show a poor response to cytotoxic drugs, and thus the detailed mechanism of this resistance needs to be further investigated. Our previous research indicated th...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research
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