Displaying publications 1 - 20 of 53 in total

Abstract:
Sort:
  1. Al-Obaidy R, Haider AJ, Al-Musawi S, Arsad N
    Sci Rep, 2023 Feb 23;13(1):3180.
    PMID: 36823237 DOI: 10.1038/s41598-023-30221-x
    Fibrosarcoma is a rare type of cancer that affects cells known as fibroblasts that are malignant, locally recurring, and spreading tumor in fibrous tissue. In this work, an iron plate immersed in an aqueous solution of double added deionized water, supplemented with potassium permanganate solution (KMnO4) was carried out by the pulsed laser ablation in liquid method (PLAIL). Superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized using different laser wavelengths (1064, 532, and 266 nm) at a fluence of 28 J/cm2 with 100 shots of the iron plate to control the concentration, shape and size of the prepared high-stability SPIONs. The drug nanocarrier was synthesized by coating SPION with paclitaxel (PTX)-loaded chitosan (Cs) and polyethylene glycol (PEG). This nanosystem was functionalized by receptors that target folate (FA). The physiochemical characteristics of SPION@Cs-PTX-PEG-FA nanoparticles were evaluated and confirmed by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-Ray diffraction (XRD), atomic force microscopy (AFM), and dynamic light scattering (DLS) methods. Cell internalization, cytotoxicity assay (MTT), apoptosis induction, and gene expression of SPION@Cs-PTX-PEG-FA were estimated in fibrosarcoma cell lines, respectively. In vivo studies used BALB/c tumor-bearing mice. The results showed that SPION@Cs-PTX-PEG-FA exhibited suitable physical stability, spherical shape, desirable size, and charge. SPION@Cs-PTX-PEG-FA inhibited proliferation and induced apoptosis of cancer cells (P 
    Matched MeSH terms: Paclitaxel/pharmacology; Paclitaxel/therapeutic use; Paclitaxel/chemistry
  2. Sreeharsha N, Prasanthi S, Mahalakshmi SVVNS, Goudanavar PS, Naveen NR, Gowthami B, et al.
    Molecules, 2022 Nov 16;27(22).
    PMID: 36432014 DOI: 10.3390/molecules27227914
    A brand-new nano-crystal (NC) version of the hydrophobic drug Paclitaxel (PT) were formulated for cancer treatment. A stable NC formulation for the administration of PT was created using the triblock co-polymer Pluronic F127. To achieve maximum entrapment effectiveness and minimal particle size, the formulation was improved using the central composite design by considering agitation speed and vacuum pressure at five levels (coded as +1.414, +1, 0, -1, and -1.414). According to the Design Expert software's predictions, 13 runs were created and evaluated for the chosen responses. The formulation prepared with an agitation speed of 1260 RPM and a vacuum pressure of 77.53 mbar can meet the requirements of the ideal formulation in order to achieve 142.56 nm of PS and 75.18% EE, according to the level of desirability (D = 0.959). Folic acid was conjugated to Pluronic F127 to create folate receptor-targeted NC. The drug release profile of the nano-crystals in vitro demonstrated sustained release over an extended period. Folate receptor (FR)-targeted NC (O-PT-NC-Folate) has also been prepared by conjugating folic acid to Pluronic F127. MTT test is used to validate the targeting efficacy on the FR-positive human oral cancer cell line (KB). At pharmacologically relevant concentrations, the PT nano-crystal formulation did not cause hemolysis. Compared to non-targeted NC of PT, the O-PT-NC-Folate showed a comparable but more sustained anti-cancer effect, according to an in vivo anti-tumor investigation in NCI/ADR-RES cell lines. The remarkable anti-tumor effectiveness, minimal toxicity, and simplicity of scale-up manufacturing of the NC formulations indicate their potential for clinical development. Other hydrophobic medications that are formulated into nano-systems for improved therapy may benefit from the formulation approach.
    Matched MeSH terms: Paclitaxel/pharmacology
  3. Ahmad S, Lambuk L, Ahmed N, Mussa A, Tee V, Mohd Idris RA, et al.
    Nanomedicine (Lond), 2023 Oct;18(24):1733-1744.
    PMID: 37982749 DOI: 10.2217/nnm-2022-0300
    Background: Nab-paclitaxel is formulated to address several limitations of paclitaxel. Methods: A systematic review was done of several databases and a meta-analysis with a random-effects model was conducted to assess the efficacy and safety of nab-paclitaxel in metastatic gastric cancer (MGC). Results: Included studies revealed that nab-paclitaxel provides a 30.4% overall response rate and 65.7% disease control rate in MGC patients. The overall survival was 9.65 months and progression-free survival was 4.48 months, associated with the treatment line and regimen. The highest incidence of grade 3 and higher treatment-related adverse events was for neutropenia (29.9%). Conclusion: Nab-paclitaxel provides better disease response and longer survival with manageable side effects in MGC compared with paclitaxel.
    Matched MeSH terms: Paclitaxel/adverse effects
  4. Gorain B, Choudhury H, Pandey M, Kesharwani P
    Mater Sci Eng C Mater Biol Appl, 2018 Oct 01;91:868-880.
    PMID: 30033322 DOI: 10.1016/j.msec.2018.05.054
    Localised and targeted potential of nanocarrier for the eminent anticancer agent paclitaxel (PTX) could provide a great platform towards improvement of efficacy with reduction in associated toxicities, whereas incorporation of TPGS could further facilitate delivery in MDR through alteration of its inherent physicochemical properties. Current article therefore puts into perspective on nanocarrier-based recent researches of PTX with special stress towards TPGS-nanoparticle-mediated delivery in the improvement of cancer treatment and then accompanied with the discussion on distinct influence of the fabrication process. Such dynamic fabrications of the nanoparticulate therapy stimulate cellular interaction with frontier area for future research in tumor targeting potential.
    Matched MeSH terms: Paclitaxel
  5. Jabir RS, Naidu R, Annuar MA, Ho GF, Munisamy M, Stanslas J
    Pharmacogenomics, 2012 Dec;13(16):1979-88.
    PMID: 23215890 DOI: 10.2217/pgs.12.165
    Interindividual variability in drug response and the emergence of adverse drug effects are the main causes of treatment failure in cancer therapy. Functional membrane drug transporters play important roles in altering pharmacokinetic profile, resistance to treatment, toxicity and patient survival. Pharmacogenetic studies of these transporters are expected to provide new approaches for optimizing therapy. Taxanes are approved for the treatment of various cancers. Circulating taxanes are taken up by SLCO1B3 into hepatocytes. The CYP450 enzymes CYP3A4, CYP3A5 and CYP2C8 are responsible for the conversion of taxanes into their metabolites. Ultimately, ABCB1 and ABCC2 will dispose the metabolites into bile canaliculi. Polymorphisms of genes encoding for proteins involved in the transport and clearance of taxanes reduce excretion of the drugs, leading to development of toxicity in patients. This review addresses current knowledge on genetic variations of transporters affecting taxanes pharmacokinetics and toxicity, and provides insights into future direction for personalized medicine.
    Matched MeSH terms: Paclitaxel/therapeutic use
  6. Otto S, Díaz VAJ, Weilenmann D, Cuculi F, Nuruddin AA, Leibundgut G, et al.
    BMC Cardiovasc Disord, 2023 Mar 31;23(1):176.
    PMID: 37003986 DOI: 10.1186/s12872-023-03187-x
    BACKGROUND: A decade ago, the iopromide-paclitaxel coated balloon (iPCB) was added to the cardiologist's toolbox to initially treat in-stent restenosis followed by the treatment of de novo coronary lesions. In the meantime, DES technologies have been substantially improved to address in-stent restenosis and thrombosis, and shortened anti-platelet therapy. Recently, sirolimus-coated balloon catheters (SCB) have emerged to provide an alternative drug to combat restenosis.

    METHODS: The objective of this study is to determine the safety and efficacy of a novel crystalline sirolimus-coated balloon (cSCB) technology in an unselective, international, large-scale patient population. Percutaneous coronary interventions of native stenosis, in-stent stenosis, and chronic total occlusions with the SCB in patients with stable coronary artery disease or acute coronary syndrome were included. The primary outcome variable is the target lesion failure (TLF) rate at 12 months, defined as the composite rate of target vessel myocardial infarction (TV-MI), cardiac death or ischemia-driven target lesion revascularization (TLR). The secondary outcome variables include TLF at 24 months, ischemia driven TLR at 12 and 24 months and all-cause death, cardiac death at 12 and 24 months.

    DISCUSSION: Since there is a wealth of patient-based all-comers data for iPCB available for this study, a propensity-score matched analysis is planned to compare cSCB and iPCB for the treatment of de novo and different types of ISR. In addition, pre-specified analyses in challenging lesion subsets such as chronic total occlusions will provide evidence whether the two balloon coating technologies differ in their clinical benefit for the patient.

    TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04470934.

    Matched MeSH terms: Paclitaxel/adverse effects
  7. Linn YL, Wang JC, Pua U, Yahaya SA, Choke ET, Chong TT, et al.
    Vascular, 2023 Aug;31(4):767-776.
    PMID: 35410542 DOI: 10.1177/17085381221081969
    BACKGROUND: Results from the BIOLUX P-III registry have demonstrated favourable outcomes of Passeo-18 Lux™ (Biotronik®, Buelach, Switzerland) drug-coated balloon in treating obstructive infrainguinal peripheral artery disease, but it has not been established if Asians would benefit to the same extent as non-Asians.

    METHODS: A subgroup analysis was performed on the 24-month data comparing the Asian cohort (AC) to non-Asian cohort (NAC).

    RESULTS: AC included 49 patients with 77 lesions. AC was significantly younger (65.6 vs 70.3 years, p < 0.05), had more diabetes (87.8% vs 45.3%, p < 0.05), and was more likely to present with CLTI (73.5% vs 35.3%, p < 0.001) compared to NAC. They had significantly longer mean target lesions (115 vs 86.9 mm, p = 0.006), and received significantly higher paclitaxel doses (10.7 vs 7.2 mg, p = 0.0005). Device, technical and procedural successes were 125/125(100%), 95/97(97.5%) and 45/49(91.8%), respectively. There was no significant difference in target lesion revascularization rates between groups (10.5% vs 12%, p = 0.91). However, the AC had more major adverse events (30.2% vs 16.1%, p = 0.001), amputations (26.3% vs 6.2%, p < 0.05) and mortality (37.9% vs 10.6%, p < 0.05) at 24 months.

    CONCLUSION: Passeo-18 Lux™ use was efficacious in Asians, but was associated with higher adverse events, amputations and mortality rates, likely attributable to poorer patient comorbidities and more extensive PAD.

    Matched MeSH terms: Paclitaxel/adverse effects
  8. Nor Fadilah Rajab, Chan Kok Meng, Nur Hasnieza Mohd Rosli, Fariza Juliana Nordin, Leong Lek Mun, Nur Syazwani Abdul Aziz
    Jurnal Sains Kesihatan Malaysia, 2018;16(101):95-103.
    MyJurnal
    ABSTRACT
    Clinacanthus nutans (C. nutans) leaf extracts have been widely used by cancer patients in Malaysia and local practice claims a cure to cancer. There were several studies done to determine the cytotoxicity potency of C. nutans extracts on various types of cells. However, there is still lacking on the knowledge regarding the combination effect of C. nutans with anticancer drugs. Thus, the study was carried out to determine the cytotoxicity potency of C. nutans extracts and paclitaxel (PTX) alone and, in combination on MDA-MB-231 cells. The cells were treated with 100% ethanol extract of C. nutans (CNE) and water extract of C. nutans (CNA), PTX and combination of both extracts and PTX for 72 hours and the cytotoxic activity was determined using SRB assay. Result showed that CNE had little cytotoxic activity, whereas CNA showed no cytotoxic activity on MDA-MB-231 cells. For combination treatment of C. nutans extracts and PTX, only CNE showed significant enhanced PTX-induced cytotoxicity (p < 0.05), meanwhile CNA inhibited PTX-induced cytotoxicity significantly (p < 0.05). As a conclusion, CNE was able to increase PTX potency to inhibit the viability of MDA-MB-231 cells.
    Matched MeSH terms: Paclitaxel
  9. Ayub AD, Chiu HI, Mat Yusuf SNA, Abd Kadir E, Ngalim SH, Lim V
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):353-369.
    PMID: 30691309 DOI: 10.1080/21691401.2018.1557672
    The application of layer-by-layer (LbL) approach on nanoparticle surface coating improves the colon-specific drug delivery of insoluble drugs. Here, we aimed to formulate a self-assembled cysteamine-based disulphide cross-linked sodium alginate with LbL self-assembly to improve the delivery of paclitaxel (PCX) to colonic cancer cells. Cysteamine was conjugated to the backbone of oxidized SA to form a core of self-assembled disulphide cross-linked nanospheres. P3DL was selected for PCX loading and fabricated LbL with poly(allylamine hydrochloride) (PAH) and poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSCMA) resulting from characterization and drug release studies. P3DL-fabricated PCX-loaded nanospheres (P3DL/PAH/PSSCMA) exhibited an encapsulation efficiency of 77.1% with cumulative drug release of 45.1%. Dynamic light scattering analysis was reported at 173.6 ± 2.5 nm with polydispersity index of 0.394 ± 0.105 (zeta potential= -58.5 mV). P3DL/PAH/PSSCMA demonstrated a pH-dependent swelling transition; from pH 1 to 7 (102.2% increase). The size increased by 33.0% in reduction response study after incubating with 10 mM glutathione (day 7). HT-29 cells showed high viabilities (86.7%) after treatment with the fabricated nanospheres at 0.8 µg/mL. Cellular internalization was successful with more than 70.0% nanospheres detected in HT-29 cells. Therefore, this fabricated nanospheres may be considered as potential nanocarriers for colon cancer-targeted chemotherapeutic drug delivery.
    Matched MeSH terms: Paclitaxel/administration & dosage*; Paclitaxel/metabolism; Paclitaxel/chemistry*
  10. Mansor AFM, Ibrahim I, Zainuddin AA, Voiculescu I, Nordin AN
    Med Biol Eng Comput, 2018 Jan;56(1):173-181.
    PMID: 29247387 DOI: 10.1007/s11517-017-1756-1
    Electrical cell-substrate impedance sensing (ECIS) is a powerful technique to monitor real-time cell behavior. In this study, an ECIS biosensor formed using two interdigitated electrode structures (IDEs) was used to monitor cell behavior and its response to toxicants. Three different sensors with varied electrode spacing were first modeled using COMSOL Multiphysics and then fabricated and tested. The silver/silver chloride IDEs were fabricated using a screen-printing technique and incorporated with polydimethylsiloxane (PDMS) cell culture wells. To study the effectiveness of the biosensor, A549 lung carcinoma cells were seeded in the culture wells together with collagen as an extracellular matrix (ECM) to promote cell attachment on electrodes. A549 cells were cultured in the chambers and impedance measurements were taken at 12-h intervals for 120 h. Cell index (CI) for both designs were calculated from the impedance measurement and plotted in comparison with the growth profile of the cells in T-flasks. To verify that the ECIS biosensor can also be used to study cell response to toxicants, the A549 cells were also treated with anti-cancer drug, paclitaxel, and its responses were monitored over 5 days. Both simulation and experimental results show better sensitivity for smaller spacing between electrodes. Graphical abstract The fabricated impedance biosensor used screen-printed silver/silver chloride IDEs. Simulation and experimental results show better sensitivity for smaller between electrodes.
    Matched MeSH terms: Paclitaxel/pharmacology; Paclitaxel/therapeutic use
  11. Tibon NS, Ng CH, Cheong SL
    Eur J Med Chem, 2020 Feb 15;188:111983.
    PMID: 31911292 DOI: 10.1016/j.ejmech.2019.111983
    Discovery and development of antimalarial drugs have long been dominated by single-target therapy. Continuous effort has been made to explore and identify different targets in malaria parasite crucial for the malaria treatment. The single-target drug therapy was initially successful, but it was later supplanted by combination therapy with multiple drugs to overcome drug resistance. Emergence of resistant strains even against the combination therapy has warranted a review of current antimalarial pharmacotherapy. This has led to the development of the new concept of covalent biotherapy, in which two or more pharmacophores are chemically bound to produce hybrid antimalarial drugs with multi-target functionalities. Herein, the review initially details the current pharmacotherapy for malaria as well as the conventional and novel targets of importance identified in the malaria parasite. Then, the rationale of multi-targeted therapy for malaria, approaches taken to develop the multi-target antimalarial hybrids, and the examples of hybrid molecules are comprehensively enumerated and discussed.
    Matched MeSH terms: Paclitaxel/pharmacology*; Paclitaxel/chemistry
  12. Ali MK, Moshikur RM, Wakabayashi R, Moniruzzaman M, Goto M
    ACS Appl Mater Interfaces, 2021 May 05;13(17):19745-19755.
    PMID: 33891816 DOI: 10.1021/acsami.1c03111
    Chemotherapeutic cytotoxic agents such as paclitaxel (PTX) are considered essential for the treatment of various cancers. However, PTX injection is associated with severe systemic side effects and high rates of patient noncompliance. Micelle formulations (MFs) are nano-drug delivery systems that offer a solution to these problems. Herein, we report an advantageous carrier for the transdermal delivery of PTX comprising a new MF that consists of two biocompatible surfactants: cholinium oleate ([Cho][Ole]), which is a surface-active ionic liquid (SAIL), and sorbitan monolaurate (Span-20). A solubility assessment confirmed that PTX was readily solubilized in the SAIL-based micelles via multipoint hydrogen bonding and cation-π and π-π interactions between PTX and SAIL[Cho][Ole]. Dynamic light scattering (DLS) and transmission electron microscopy revealed that in the presence of PTX, the MF formed spherical PTX-loaded micelles that were well-distributed in the range 8.7-25.3 nm. According to DLS, the sizes and size distributions of the micelle droplets did not change significantly over the entire storage period, attesting to their physical stability. In vitro transdermal assessments using a Franz diffusion cell revealed that the MF absorbed PTX 4 times more effectively than a Tween 80-based formulation and 6 times more effectively than an ethanol-based formulation. In vitro and in vivo skin irritation tests revealed that the new carrier had a negligible toxicity profile compared with a conventional ionic liquid-based carrier. Based on these findings, we believe that the SAIL[Cho][Ole]-based MF has potential as a biocompatible nanocarrier for the effective transdermal delivery of poorly soluble chemotherapeutics such as PTX.
    Matched MeSH terms: Paclitaxel/administration & dosage*; Paclitaxel/pharmacokinetics
  13. Vijayan V, Shalini K, Yugesvaran V, Yee TH, Balakrishnan S, Palanimuthu VR
    Curr Pharm Des, 2018;24(28):3366-3375.
    PMID: 30179118 DOI: 10.2174/1381612824666180903110301
    BACKGROUND: Triple-Negative Breast Cancer is an aggressive type of breast cancer, which is not treatable by chemotherapy drugs, due to the lack of Estrogen Receptor (ER), Progesterone Receptor (PR) expression and Human Epidermal Growth Factor Receptor 2 (HER2) on the cell surface.

    OBJECTIVE: The aim of this study was to compare the effect of paclitaxel loaded PLGA nanoparticle (PTX-NPs) on the cytotoxicity and apoptosis of the different MDA-MB type of cell lines.

    METHOD: PTX-NPs were prepared by nanoprecipitation method and characterized earlier. The cytotoxicity of PTX-NPs was evaluated by MTT and LDH assay, later apoptosis was calculated by flow cytometry analysis.

    RESULTS: The prepared NP size of 317.5 nm and zetapontial of -12.7 mV showed drug release of 89.1 % at 48 h. MDA-MB-231 type cell showed significant cytotoxicity by MTT method of 47.4 ± 1.2 % at 24 h, 34.6 ± 0.8 % at 48 h and 23.5 ± 0.5 % at 72 h and LDH method of 35.9 ± 1.5 % at 24 h, 25.4 ± 0.6 % at 48 h and 19.8 ± 2.2 % at 72 h with apoptosis of 47.3 ± 0.4 %.

    CONCLUSION: We have found that PTX-NPs showed the cytotoxic effect on all the MDA-MB cancer cell lines and showed potent anticancer activities against MDA-MB-231 cell line via induction of apoptosis.

    Matched MeSH terms: Paclitaxel/pharmacology*; Paclitaxel/chemistry
  14. Geetha Bai R, Muthoosamy K, Shipton FN, Manickam S
    Ultrason Sonochem, 2017 May;36:129-138.
    PMID: 28069192 DOI: 10.1016/j.ultsonch.2016.11.021
    Graphene is one of the highly explored nanomaterials due to its unique and extraordinary properties. In this study, by utilizing a hydrothermal reduction method, graphene oxide (GO) was successfully converted to reduced graphene oxide (RGO) without using any toxic reducing agents. Following this, with the use of ultrasonic cavitation, profoundly stable few layer thick RGO nanodispersion was generated without employing any stabilizers or surfactants. During ultrasonication, shockwaves from the collapse of bubbles cause a higher dispersing energy to the graphene nanosheets which surpass the forces of Van der Waal's and π-π stacking and thus pave the way to form a stable aqueous nanodispersion of graphene. Ultrasonication systems with different power intensity have been employed to determine the optimum conditions for obtaining the most stable RGO dispersion. The optimised conditions of ultrasonic treatments led to the development of a very stable reduced graphene oxide (RGO) aqueous dispersion. The stability was observed for two years and was analyzed by using Zetasizer by measuring the particle size and zeta potential at regular intervals and found to have exceptional stability. The excellent stability at physiological pH promotes its utilization in nano drug delivery application as a carrier for Paclitaxel (Ptx), an anticancer drug. The in vitro cytotoxicity analysis of Ptx loaded RGO nanodispersion by MTT assay performed on the cell lines revealed the potential of the nanodispersion as a suitable drug carrier. Studies on normal lung cells, MRC-5 and nasopharyngeal cancer cells, HK-1 supported the biocompatibility of RGO-Ptx towards normal cell line. This investigation shows the potential of exceptionally stable RGO-Ptx nanodispersion in nano drug delivery applications.
    Matched MeSH terms: Paclitaxel/chemistry*
  15. Singh R, Ting JG, Pan Y, Teh LK, Ismail R, Ong CE
    Drug Metab. Pharmacokinet., 2008;23(3):165-74.
    PMID: 18574320
    The work described in this study aimed to express CYP2C8 wild-type and mutant proteins in bacterial expression system and to use the expressed proteins to investigate the structural and functional consequences of a reported allele CYP2C8(*)4 (carrying Ile264Met substitution) on protein activity. Ile264 was replaced by three different amino acids resulting in three mutant constructs, 2C8I264M, 2C8I264R and 2C8I264D. The presence of isoleucine at position 264 in CYP2C8 was found to be important for proper haem insertion and protein folding; whereas bulkier or charged residues were highly disruptive resulting in inactive proteins with minimum spectral and catalytic activities. This was evidenced from the low levels of Soret peak at 450 nm and negligible levels of tolbutamide methylhydroxylase activity. Kinetic study using paclitaxel indicated that all three mutants exhibited only 9.7 to 35.4% of the activity level observed in the wild-type. In addition, the mutants were more sensitive to proteinase K digestion, indicating a possible alteration of conformation. The combined effects of protein instability and compromised catalytic activity resulted in defective CYP2C8 protein which may have clinical implications in carriers of CYP2C8*4, particularly in terms of their capacity to clear potent drugs and their susceptibility to adverse drug reactions.
    Matched MeSH terms: Paclitaxel/metabolism; Paclitaxel/pharmacology
  16. Chowdhury MR, Moshikur RM, Wakabayashi R, Tahara Y, Kamiya N, Moniruzzaman M, et al.
    Mol Pharm, 2018 06 04;15(6):2484-2488.
    PMID: 29762034 DOI: 10.1021/acs.molpharmaceut.8b00305
    Paclitaxel (PTX) injection (i.e., Taxol) has been used as an effective chemotherapeutic treatment for various cancers. However, the current Taxol formulation contains Cremophor EL, which causes hypersensitivity reactions during intravenous administration and precipitation by aqueous dilution. This communication reports the preliminary results on the ionic liquid (IL)-based PTX formulations developed to address the aforementioned issues. The formulations were composed of PTX/cholinium amino acid ILs/ethanol/Tween-80/water. A significant enhancement in the solubility of PTX was observed with considerable correlation with the density and viscosity of the ILs, and with the side chain of the amino acids used as anions in the ILs. Moreover, the formulations were stable for up to 3 months. The driving force for the stability of the formulation was hypothesized to be the involvement of different types of interactions between the IL and PTX. In vitro cytotoxicity and antitumor activity of the IL-based formulations were evaluated on HeLa cells. The IL vehicles without PTX were found to be less cytotoxic than Taxol, while both the IL-based PTX formulation and Taxol exhibited similar antitumor activity. Finally, in vitro hypersensitivity reactions were evaluated on THP-1 cells and found to be significantly lower with the IL-based formulation than Taxol. This study demonstrated that specially designed ILs could provide a potentially safer alternative to Cremophor EL as an effective PTX formulation for cancer treatment giving fewer hypersensitivity reactions.
    Matched MeSH terms: Paclitaxel/adverse effects*; Paclitaxel/chemistry
  17. Hama M, Ishima Y, Chuang VTG, Ando H, Shimizu T, Ishida T
    ACS Appl Mater Interfaces, 2021 May 05;13(17):19736-19744.
    PMID: 33881292 DOI: 10.1021/acsami.1c03065
    Abraxane, an albumin-bound paclitaxel nanoparticle formulation, is superior to conventional paclitaxel preparations because it has better efficacy against unresectable pancreatic cancer. Previous reports suggest that this better efficacy of Abraxane than conventional paclitaxel preparation is probably due to its transport through Gp60, an albumin receptor on the surface of vascular endothelial cells. The increased tumor accumulation of Abraxane is also caused by the secreted protein acid and rich in cysteine in the tumor stroma. However, the uptake mechanism of Abraxane remains poorly understood. In this study, we demonstrated that the delivery of Abraxane occurred via different receptor pathways from that of endogenous albumin. Our results showed that the uptake of endogenous albumin was inhibited by a Gp60 pathway inhibitor in the process of endocytosis through endothelial cells or tumor cells. In contrast, the uptake of Abraxane-derived HSA was less affected by the Gp60 pathway inhibitor but significantly reduced by denatured albumin receptor inhibitors. In conclusion, these data indicate that Abraxane-derived HSA was taken up into endothelial cells or tumor cells by a mechanism different from normal endogenous albumin. These new data on distinct cellular transport pathways of denatured albumin via gp family proteins different from those of innate albumin shed light on the mechanisms of tumor delivery and antitumor activity of Abraxane and provide new scientific rationale for the development of a novel albumin drug delivery strategy via a denatured albumin receptor.
    Matched MeSH terms: Albumin-Bound Paclitaxel/administration & dosage*; Albumin-Bound Paclitaxel/chemistry
  18. Chowdhury MR, Moshikur RM, Wakabayashi R, Tahara Y, Kamiya N, Moniruzzaman M, et al.
    Int J Pharm, 2019 Jun 30;565:219-226.
    PMID: 31077761 DOI: 10.1016/j.ijpharm.2019.05.020
    In order to prevent common hypersensitivity reactions to paclitaxel injections (Taxol), we previously reported an ionic liquid-mediated paclitaxel (IL-PTX) formulation with small particle size and narrow size distribution. The preliminary work showed high PTX solubility in the IL, and the formulation demonstrated similar antitumor activity to Taxol, while inducing a smaller hypersensitivity effect in in vitro cell experiments. In this study, the stability of the IL-PTX formulation was monitored by quantitative HPLC analysis, which showed that IL-PTX was more stable at 4 °C than at room temperature. The in vivo study showed that the IL-PTX formulation could be used in a therapeutic application as a biocompatible component of a drug delivery system. To assess the in-vivo biocompatibility, IL or IL-mediated formulations were administered intravenously by maintaining physiological buffered conditions (neutral pH and isotonic salt concentration). From in vivo pharmacokinetics data, the IL-PTX formulation was found to have a similar systemic circulation time and slower elimination rate compared to cremophor EL mediated paclitaxel (CrEL-PTX). Furthermore, in vivo antitumor and hypersensitivity experiments in C57BL/6 mice revealed that IL-PTX had similar antitumor activity to CrEL-PTX, but a significantly smaller hypersensitivity effect compared with CrEL-PTX. Therefore, the IL-mediated formulation has potential to be an effective and safe drug delivery system for PTX.
    Matched MeSH terms: Paclitaxel/administration & dosage*; Paclitaxel/pharmacokinetics
  19. Venugopal V, Krishnan S, Palanimuthu VR, Sankarankutty S, Kalaimani JK, Karupiah S, et al.
    PLoS One, 2018;13(11):e0206109.
    PMID: 30408068 DOI: 10.1371/journal.pone.0206109
    The aim of the present study is to analyze the viability of anti-EGFR anchored immunonanoparticle (INP) bearing Paclitaxel (PTX) to specifically bind the EGFR protein on the TNBC cells. The NP was prepared by nanoprecipitation and characterized the particle size, charge, entrapment of drug and release of it. The anti-EGFR anchored and the integrity was confirmed by SDS-PAGE. Cytotoxicity and NPs cellular uptake was analyzed with MDA-MB-468 type cancer cells and the EGFR expression was confirmed by PCR, qualitatively and quantitatively. The in-vivo antitumor activity of INP was determined by using athymic mice model and targeting efficiency was measured by calculating the PTX accumulation in the tumor plasma. The prepared INP with the size of 336.3 nm and the charge of -3.48 mV showed sustained drug release upto 48 h. The INP showed significant reduction of cancer cell viability of 10.6% for 48 h with 93 fold higher PTX accumulation in the tumor plasma compared with NPs. Based on these reports, we recommend that anti-EGFR anchored PTX loaded NP may have the ability to target the TNBC cells and improve the therapeutic action and subsidize the side effects of PTX for the treatment of TNBC.
    Matched MeSH terms: Paclitaxel/administration & dosage*; Paclitaxel/chemistry
  20. Matsusaka K, Ishima Y, Maeda H, Kinoshita R, Ichimizu S, Taguchi K, et al.
    J Pharm Sci, 2019 11;108(11):3592-3598.
    PMID: 31288036 DOI: 10.1016/j.xphs.2019.07.002
    Nanosize plasma proteins could be used as a biomimetic drug delivery system (DDS) for cancer treatment when loaded with anticancer drugs based on the fact that plasma proteins can serve as a source of nutrients for cancer cells. This prompted us to investigate the potential of α1-acid glycoprotein (AGP) for this role because it is a nanosize plasma protein and binds a variety of anticancer agents. Pharmacokinetic analyses indicated that AGP is distributed more extensively in tumor tissue than human serum albumin, which was already established as a cancer DDS carrier. AGP is possibly being incorporated into tumor cells via endocytosis pathways. Moreover, a synthetic AGP-derived peptide which possesses a high ability to form an α-helix, as deduced from the primary structure of AGP, was also taken up by the tumor cells. AGP loaded with anticancer agents, such as paclitaxel or nitric oxide, efficiently induced tumor cell death. These results suggest that AGP has the potential to be a novel DDS carrier for anticancer agents.
    Matched MeSH terms: Paclitaxel/administration & dosage; Paclitaxel/chemistry
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links