Displaying publications 1 - 20 of 97 in total

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  1. Hussain Z, Khan S, Imran M, Sohail M, Shah SWA, de Matas M
    Drug Deliv Transl Res, 2019 06;9(3):721-734.
    PMID: 30895453 DOI: 10.1007/s13346-019-00631-4
    On account of heterogeneity, intrinsic ability of drug resistance, and the potential to invade to other parts of the body (malignancy), the development of a rational anticancer regimen is dynamically challenging. Chemotherapy is considered the gold standard for eradication of malignancy and mitigation of its reoccurrence; nevertheless, it has also been associated with detrimental effects to normal tissues owing to its nonselectivity and nominal penetration into the tumor tissues. In recent decades, nanotechnology-guided interventions have been well-acclaimed due to their ability to facilitate target-specific delivery of drugs, avoidance of nontarget distribution, alleviated systemic toxicity, and maximized drug internalization into cancer cells. Despite their numerous biomedical advantages, clinical translation of nanotechnology-mediated regimens is challenging due to their short plasma half-life and early clearance. PEGylation of nanomedicines has been adapted as an efficient strategy to extend plasma half-life and diminished early plasma clearance via alleviating the opsonization (uptake by monocytes and macrophages) of drug nanocarriers. PEGylation provides "stealth" properties to nanocarrier's surfaces which diminished their recognition or uptake by cellular immune system, leading to longer circulation time, reduced dosage and frequency, and superior site-selective delivery of drugs. Therefore, this review aims to present a comprehensive overview of the pharmaceutical advantages and therapeutic feasibility of PEGylation of nanocarriers in improving tumor-specific targetability, reversing drug resistance, and improving pharmacokinetic profile of drugs and anticancer efficacy. Challenges to PEGylated cancer nanomedicines, possible adaptations to resolve those challenges, and pivotal requirement for interdisciplinary research for development of rational anticancer regimen have also been pondered.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  2. Win TT, Sitiasma H, Zeehaida M
    Trop Biomed, 2011 Apr;28(1):64-7.
    PMID: 21602770
    Infections and mTalignancies are common causes of pleural effusion. Among infectious causes, hyperinfection syndrome of Strongyloides stercoralis may occur in immunosuppressive patient. A 62-year-old man, known case of Non-Hodgkin lymphoma (NHL) was presented with recurrent NHL stage IV and had undergone salvage chemotherapy. Patient subsequently developed pneumonia with bilateral pleural effusion and ascites. We reported rhabditiform larvae of S. stercoralis in pleural fluid of both lungs without infiltration by lymphoma cells. Stool for microscopic examination also revealed rhabditiform larvae of S. stercoralis. This patient was a known case of NHL receiving chemotherapy resulting in immunosuppression state. Although S. stercoralis infection is not very common compared to other parasitic infections, it is common in immunosuppressive patients and may present with hyperinfection. Therefore, awareness of this parasite should be kept in mind in immunosuppressive patients.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  3. Hammadi NI, Abba Y, Hezmee MNM, Razak ISA, Kura AU, Zakaria ZAB
    In Vitro Cell Dev Biol Anim, 2017 Dec;53(10):896-907.
    PMID: 28916966 DOI: 10.1007/s11626-017-0197-3
    Cockle shell-derived calcium carbonate nanoparticles have shown promising potentials as slow drug-releasing compounds in cancer chemotherapy. In this study, we evaluated the in vitro efficacy of docetaxel (DTX)-loaded CaCO3NP on 4T1 cell line. This was achieved by evaluating the following: cytotoxicity using MTT assay, fluorescence imaging, apoptosis with Annexin V assay, cell cycle analysis, scanning (SEM) and transmission electron microscopy (TEM), and scratch assay. Based on the results, DTX-CaCO3NP with a DTX concentration of 0.5 μg/mL and above had comparable cytotoxic effects with free DTX at 24 h, while all concentrations had similar cytotoxic effect on 4T1 cells at 48 and 72 h. Fluorescence and apoptosis assay showed a higher (p 
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  4. Shafiu Kamba A, Ismail M, Tengku Ibrahim TA, Zakaria ZA
    Biomed Res Int, 2013;2013:587451.
    PMID: 24324966 DOI: 10.1155/2013/587451
    The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO₃/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO₃/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells. In vitro chemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO₃/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO₃ nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  5. Tahir AA, Sani NF, Murad NA, Makpol S, Ngah WZ, Yusof YA
    Nutr J, 2015;14:31.
    PMID: 25889965 DOI: 10.1186/s12937-015-0015-2
    The interconnected Ras/ERK and PI3K/AKT pathways play a central role in colorectal tumorigenesis, and they are targets for elucidating mechanisms involved in attempts to induce colon cancer cell death. Both ginger (Zingiber officinale) and honey have been shown to exhibit anti-tumor and anti-inflammation properties against many types of cancer, including colorectal cancer. However, there are currently no reports showing the combined effect of these two dietary compounds in cancer growth inhibition. The aim of this study was to evaluate the synergistic effect of crude ginger extract and Gelam honey in combination as potential cancer chemopreventive agents against the colorectal cancer cell line HT29.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  6. Viswanathan G, Hsu YH, Voon SH, Imae T, Siriviriyanun A, Lee HB, et al.
    Macromol Biosci, 2016 06;16(6):882-95.
    PMID: 26900760 DOI: 10.1002/mabi.201500435
    Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P71 D3 )-based micelles effectively encapsulate the doxorubicin (DOX) with a high drug-loading capacity (≈95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P296 D1 ) vesicles. DOX released from the resultant P71 D3 /DOX micelles is approximately 1.3-fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P71 D3 /DOX micelles also enhance drug potency in breast cancer MDA-MB-231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy-dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  7. Namvar F, Rahman HS, Mohamad R, Baharara J, Mahdavi M, Amini E, et al.
    Int J Nanomedicine, 2014;9:2479-88.
    PMID: 24899805 DOI: 10.2147/IJN.S59661
    Magnetic iron oxide nanoparticles (Fe3O4 MNPs) are among the most useful metal nanoparticles for multiple applications across a broad spectrum in the biomedical field, including the diagnosis and treatment of cancer. In previous work, we synthesized and characterized Fe3O4 MNPs using a simple, rapid, safe, efficient, one-step green method involving reduction of ferric chloride solution using brown seaweed (Sargassum muticum) aqueous extract containing hydroxyl, carboxyl, and amino functional groups mainly relevant to polysaccharides, which acts as a potential stabilizer and metal reductant agent. The aim of this study was to evaluate the in vitro cytotoxic activity and cellular effects of these Fe3O4 MNPs. Their in vitro anticancer activity was demonstrated in human cell lines for leukemia (Jurkat cells), breast cancer (MCF-7 cells), cervical cancer (HeLa cells), and liver cancer (HepG2 cells). The cancer cells were treated with different concentrations of Fe3O4 MNPs, and an MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was used to test for cytotoxicity, resulting in an inhibitory concentration 50 (IC50) value of 23.83±1.1 μg/mL (HepG2), 18.75±2.1 μg/mL (MCF-7), 12.5±1.7 μg/mL (HeLa), and 6.4±2.3 μg/mL (Jurkat) 72 hours after treatment. Therefore, Jurkat cells were selected for further investigation. The representative dot plots from flow cytometric analysis of apoptosis showed that the percentages of cells in early apoptosis and late apoptosis were increased. Cell cycle analysis showed a significant increase in accumulation of Fe3O4 MNP-treated cells at sub-G1 phase, confirming induction of apoptosis by Fe3O4 MNPs. The Fe3O4 MNPs also activated caspase-3 and caspase-9 in a time-response fashion. The nature of the biosynthesis and therapeutic potential of Fe3O4 MNPs could pave the way for further research on the green synthesis of therapeutic agents, particularly in nanomedicine, to assist in the treatment of cancer.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  8. Badran MM, Alomrani AH, Harisa GI, Ashour AE, Kumar A, Yassin AE
    Biomed Pharmacother, 2018 Oct;106:1461-1468.
    PMID: 30119220 DOI: 10.1016/j.biopha.2018.07.102
    In the present study, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA) and polycaprolactone (PCL) nanoparticles were successfully prepared and coated with chitosan (CS). The prepared nanoparticles (NPs) were evaluated for their particle size, zeta potential, particle morphology, drug entrapment efficiency (EE%), and in vitro drug release profile. The anticancer activity of DTX-loaded NPs was assessed in human HT29 colon cancer cell line utilizing MTT assay. The pharmacokinetics of DTX-loaded NPs was monitored in Wistar rats in comparison to DTX solution. The prepared NPs exhibited particle sizes in the range 177.1 ± 8.2-287.6 ± 14.3 nm. CS decorated NPs exhibited a significant increase in particle size and a switch of zeta potential from negative to positive. In addition, high EE% values were obtained for CS coated PCL NPs and PLGA NPs as 67.1 and 76.2%, respectively. Moreover, lowering the rate of DTX in vitro release was achieved within 48 h by using CS coated NPs. Furthermore, a tremendous increase in DTX cytotoxicity was observed by CS-decorated PLGA NPs compared to all other NPs including DTX-free-NPs and pure DTX. The in vivo study revealed significant enhancement in DTX bioavailability from CS-decorated PLGA NPs with more than 4-fold increase in AUC compared to DTX solution. In conclusion, CS-decorated PLGA NPs are a considerable DTX-delivery carrier with magnificent antitumor efficacy.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  9. Rengarajan T, Yaacob NS
    Eur J Pharmacol, 2016 Oct 15;789:8-16.
    PMID: 27377217 DOI: 10.1016/j.ejphar.2016.07.001
    Epidemiological studies show that consumption of diets rich in fruits and vegetables is associated with lower risks of cancer. This evidence has kindled interest into research on bioactive food components and has till date resulted in the identification of many compounds with cancer preventive and therapeutic potential. Among such compounds is fisetin (3,7,3,4-tetrahydroxyflavone), a flavonol that is commonly found in many fruits and vegetables such as apples, persimmons, grapes, kiwis, strawberries, onions and cucumbers. Fisetin has been shown to inhibit or retard the growth of various cancer cells in culture and implanted tumors in vivo. Fisetin targets many components of intracellular signaling pathways including regulators of cell survival and apoptosis, tumor angiogenic and metastatic switches by modulating a distinct set of upstream kinases, transcription factors and their regulators. Current evidence supports the idea that fisetin is a promising agent for cancer treatment. This review summarizes reported anticancer effects of fisetin, and re-emphasizes its potential therapeutic role in the treatment of cancer.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  10. Dorasamy MS, Ab A, Nellore K, Wong PF
    Biomed Pharmacother, 2019 Feb;110:29-36.
    PMID: 30458345 DOI: 10.1016/j.biopha.2018.11.010
    Malignant melanoma continues to be a fatal disease for which novel and long-term curative breakthroughs are desired. One such innovative idea would be to assess combination therapeutic treatments - by way of combining two potentially effective and very different therapy. Previously, we have shown that DHODH inhibitors, A771726 and Brequinar sodium (BQR) induced cell growth impairment in melanoma cells. Similar results were seen with DHODH RNA interference (shRNA). In the present study, we showed that combination of BQR with doxorubicin resulted in synergistic and additive cell growth inhibition in these cells. In addition, in vivo studies with this combination of drugs demonstrated an almost 90% tumor regression in nude mice bearing melanoma tumors. Cell cycle regulatory proteins, cyclin B1 and its binding partner pcdc-2 and p21 were significantly downregulated and upregulated respectively following the combined treatment. Given that we have observed synergistic effects with BQR and doxorubicin, both in vitro and in vivo, these drugs potentially represent a new combination in the targeted therapy of melanoma.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  11. Jahangirian H, Kalantari K, Izadiyan Z, Rafiee-Moghaddam R, Shameli K, Webster TJ
    Int J Nanomedicine, 2019;14:1633-1657.
    PMID: 30880970 DOI: 10.2147/IJN.S184723
    Conventional cancer treatment techniques show several limitations including low or no specificity and consequently a low efficacy in discriminating between cancer cells and healthy cells. Recent nanotechnology developments have introduced smart and novel therapeutic nanomaterials that take advantage of various targeting approaches. The use of nanotechnology in medicine and, more specifically, drug delivery is set to spread even more rapidly than it has over the past two decades. Currently, many nanoparticles (NPs) are under investigation for drug delivery including those for cancer therapy. Targeted nanomaterials bind selectively to cancer cells and greatly affect them with only a minor effect on healthy cells. Gold nanoparticles (Au-NPs), specifically, have been identified as significant candidates for new cancer therapeutic modalities because of their biocompatibility, easy functionalization and fabrication, optical tunable characteristics, and chemophysical stability. In the last decade, there has been significant research on Au-NPs and their biomedical applications. Functionalized Au-NPs represent highly attractive and promising candidates for drug delivery, owing to their unique dimensions, tunable surface functionalities, and controllable drug release. Further, iron oxide NPs due to their "superparamagnetic" properties have been studied and have demonstrated successful employment in numerous applications. In targeted drug delivery systems, drug-loaded iron oxide NPs can accumulate at the tumor site with the aid of an external magnetic field. This can lead to incremental effectiveness in drug release to the tumor site and vanquish cancer cells without harming healthy cells. In order for the application of iron oxide NPs in the human body to be realized, they should be biodegradable and biocompatible to minimize toxicity. This review illustrates recent advances in the field drug and small molecule delivery such as fluorouracil, folic acid, doxorubicin, paclitaxel, and daunorubicin, specifically when using gold and iron oxide NPs as carriers of anticancer therapeutic agents.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  12. Wakatsuki M, Kato S, Ohno T, Banu PA, Hoang NC, Yadamsuren E, et al.
    Int J Radiat Oncol Biol Phys, 2019 09 01;105(1):183-189.
    PMID: 31125594 DOI: 10.1016/j.ijrobp.2019.04.039
    PURPOSE: This multi-institutional observational study conducted among 11 countries in East and Southeast Asia aimed to assess the clinical outcomes of prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin for patients with locally advanced cervical cancer.

    METHODS AND MATERIALS: Between October 2007 and May 2016, 106 patients with untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiation therapy consisted of pelvic irradiation (total dose, 50 Gy in 25 fractions including central shielding), prophylactic paraortic regional irradiation (36-40 Gy in 20 fractions), and either high- or low-dose-rate intracavitary brachytherapy (ICBT) according to institutional practice. The planned point A dose was 21 to 28 Gy in 3 to 4 fractions for high-dose-rate ICBT and 40 to 41 Gy in 1 to 2 fractions for low-dose-rate ICBT. Five cycles of weekly cisplatin (40 mg/m2) were administered during the radiation therapy course.

    RESULTS: A total of 106 patients were enrolled. Of these, 9 had major protocol violations and 2 did not receive treatment because of worsened general condition. Thus, 95 patients were evaluable. The median follow-up was 56 months. Of the 95 patients, 76 (80%) received 4 or 5 cycles of chemotherapy. Acute grade 3 leukopenia was observed in 20 of the patients (21%), and late grade 3 gastrointestinal toxicity was observed in 3%. The 2-year local control, progression-free survival, and overall survival rate for all patients were 96%, 78%, and 90%, respectively.

    CONCLUSIONS: The results indicated that prophylactic extended-field concurrent chemoradiation therapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.

    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  13. Ohno T, Thinh DH, Kato S, Devi CR, Tung NT, Thephamongkhol K, et al.
    J Radiat Res, 2013 May;54(3):467-73.
    PMID: 23192700 DOI: 10.1093/jrr/rrs115
    The purpose of this study was to evaluate the efficacy and toxicity of radiotherapy concurrently with weekly cisplatin, followed by adjuvant chemotherapy, for the treatment of N2-3 nasopharyngeal cancer (NPC) in Asian countries, especially regions of South and Southeast Asian countries where NPC is endemic. Between 2005 and 2009, 121 patients with NPC (T1-4 N2-3 M0) were registered from Vietnam, Malaysia, Indonesia, Thailand, The Philippines, China and Bangladesh. Patients were treated with 2D radiotherapy concurrently with weekly cisplatin (30 mg/m (2)), followed by adjuvant chemotherapy, consisting of cisplatin (80 mg/m(2) on Day 1) and fluorouracil (800 mg/m(2) on Days 1-5) for 3 cycles. Of the 121 patients, 56 patients (46%) required interruption of RT. The reasons for interruption of RT were acute non-hematological toxicities such as mucositis, pain and dermatitis in 35 patients, hematological toxicities in 11 patients, machine break-down in 3 patients, poor general condition in 2 patients, and others in 8 patients. Of the patients, 93% completed at least 4 cycles of weekly cisplatin during radiotherapy, and 82% completed at least 2 cycles of adjuvant chemotherapy. With a median follow-up time of 46 months for the surviving 77 patients, the 3-year locoregional control, distant metastasis-free survival and overall survival rates were 89%, 74% and 66%, respectively. No treatment-related deaths occurred. Grade 3-4 toxicities of mucositis, nausea/vomiting and leukopenia were observed in 34%, 4% and 4% of the patients, respectively. In conclusion, further improvement in survival and locoregional control is necessary, although our regimen showed acceptable toxicities.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage
  14. Lee WH, Loo CY, Ghadiri M, Leong CR, Young PM, Traini D
    Adv Drug Deliv Rev, 2018 08;133:107-130.
    PMID: 30189271 DOI: 10.1016/j.addr.2018.08.012
    Lung cancer is a highly invasive and prevalent disease with ineffective first-line treatment and remains the leading cause of cancer death in men and women. Despite the improvements in diagnosis and therapy, the prognosis and outcome of lung cancer patients is still poor. This could be associated with the lack of effective first-line oncology drugs, formation of resistant tumors and non-optimal administration route. Therefore, the repurposing of existing drugs currently used for different indications and the introduction of a different method of drug administration could be investigated as an alternative to improve lung cancer therapy. This review describes the rationale and development of repositioning of drugs for lung cancer treatment with emphasis on inhalation. The review includes the current progress of repurposing non-cancer drugs, as well as current chemotherapeutics for lung malignancies via inhalation. Several potential non-cancer drugs such as statins, itraconazole and clarithromycin, that have demonstrated preclinical anti-cancer activity, are also presented. Furthermore, the potential challenges and limitations that might hamper the clinical translation of repurposed oncology drugs are described.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  15. Ma Y, Fuchs AV, Boase NR, Rolfe BE, Coombes AG, Thurecht KJ
    Eur J Pharm Biopharm, 2015 Aug;94:393-403.
    PMID: 26117186 DOI: 10.1016/j.ejpb.2015.06.014
    Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan-hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8h to 24h post-administration compared to the free NPs, due to a NP 'guarding' effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  16. Thong QX, Biabanikhankahdani R, Ho KL, Alitheen NB, Tan WS
    Sci Rep, 2019 03 08;9(1):3945.
    PMID: 30850643 DOI: 10.1038/s41598-019-40388-x
    Multifunctional nanocarriers displaying specific ligands and simultaneously response to stimuli offer great potentials for targeted and controlled drug delivery. Several synthetic thermally-responsive nanocarriers have been studied extensively for hyperthermia incorporated chemotherapy. However, no information is available on the application of virus-like particle (VLP) in thermally-controlled drug delivery systems. Here, we describe the development of a novel multifunctional nanovehicle based on the VLP of Macrobrachium rosenbergii nodavirus (MrNVLP). Folic acid (FA) was covalently conjugated to lysine residues located on the surface of MrNVLP, while doxorubicin (Dox) was loaded inside the VLP using an infusion method. This thermally-responsive nanovehicle, namely FA-MrNVLP-Dox, released Dox in a sustained manner and the rate of drug release increased in response to a hyperthermia temperature at 43 °C. The FA-MrNVLP-Dox enhanced the delivery of Dox to HT29 cancer cells expressing high level of folate receptor (FR) as compared to CCD841CoN normal cells and HepG2 cancer cells, which express low levels of FR. As a result, FA-MrNVLP-Dox increased the cytotoxicity of Dox on HT29 cells, and decreased the drug's cytotoxicity on CCD841CoN and HepG2 cells. This study demonstrated the potential of FA-MrNVLP-Dox as a thermally-responsive nanovehicle for targeted delivery of Dox to cancer cells rich in FR.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  17. Gan BK, Rullah K, Yong CY, Ho KL, Omar AR, Alitheen NB, et al.
    Sci Rep, 2020 Oct 08;10(1):16867.
    PMID: 33033330 DOI: 10.1038/s41598-020-73967-4
    Chemotherapy is widely used in cancer treatments. However, non-specific distribution of chemotherapeutic agents to healthy tissues and normal cells in the human body always leads to adverse side effects and disappointing therapeutic outcomes. Therefore, the main aim of this study was to develop a targeted drug delivery system based on the hepatitis B virus-like nanoparticle (VLNP) for specific delivery of 5-fluorouracil-1-acetic acid (5-FA) to cancer cells expressing epithelial growth factor receptor (EGFR). 5-FA was synthesized from 5-fluorouracil (5-FU), and it was found to be less toxic than the latter in cancer cells expressing different levels of EGFR. The cytotoxicity of 5-FA increased significantly after being conjugated on the VLNP. A cell penetrating peptide (CPP) of EGFR was displayed on the VLNP via the nanoglue concept, for targeted delivery of 5-FA to A431, HT29 and HeLa cells. The results showed that the VLNP displaying the CPP and harboring 5-FA internalized the cancer cells and killed them in an EGFR-dependent manner. This study demonstrated that the VLNP can be used to deliver chemically modified 5-FU derivatives to cancer cells overexpressing EGFR, expanding the applications of the VLNP in targeted delivery of chemotherapeutic agents to cancer cells overexpressing this transmembrane receptor.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  18. Wong TW, Colombo G, Sonvico F
    AAPS PharmSciTech, 2011 Mar;12(1):201-14.
    PMID: 21194013 DOI: 10.1208/s12249-010-9564-z
    Colon cancer is the fourth most common cancer globally with 639,000 deaths reported annually. Typical chemotherapy is provided by injection route to reduce tumor growth and metastasis. Recent research investigates the oral delivery profiles of chemotherapeutic agents. In comparison to injection, oral administration of drugs in the form of a colon-specific delivery system is expected to increase drug bioavailability at target site, reduce drug dose and systemic adverse effects. Pectin is suitable for use as colon-specific drug delivery vehicle as it is selectively digested by colonic microflora to release drug with minimal degradation in upper gastrointestinal tract. The present review examines the physicochemical attributes of formulation needed to retard drug release of pectin matrix prior to its arrival at colon, and evaluate the therapeutic value of pectin matrix in association with colon cancer. The review suggests that multi-particulate calcium pectinate matrix is an ideal carrier to orally deliver drugs for site-specific treatment of colon cancer as (1) crosslinking of pectin by calcium ions in a matrix negates drug release in upper gastrointestinal tract, (2) multi-particulate carrier has a slower transit and a higher contact time for drug action in colon than single-unit dosage form, and (3) both pectin and calcium have an indication to reduce the severity of colon cancer from the implication of diet and molecular biology studies. Pectin matrix demonstrates dual advantages as drug carrier and therapeutic for use in treatment of colon cancer.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  19. Adlan A, Sen DK, Sivanesaratnam V
    Med J Malaysia, 1981 Sep;36(3):159-65.
    PMID: 7329372
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
  20. Tan JR, Chakravarthi S, Judson JP, Haleagrahara N, Segarra I
    Naunyn Schmiedebergs Arch Pharmacol, 2013 Jul;386(7):619-33.
    PMID: 23552887 DOI: 10.1007/s00210-013-0861-4
    Sunitinib is a tyrosine kinase inhibitor for GIST and advanced renal cell carcinoma. Diclofenac is used in cancer pain management. Coadministration may mediate P450 toxicity. We evaluate their interaction, assessing biomarkers ALT, AST, BUN, creatinine, and histopathological changes in the liver, kidney, heart, brain, and spleen. ICR mice (male, n = 6 per group/dose) were administered saline (group A) or 30 mg/kg diclofenac ip (group B), or sunitinib po at 25, 50, 80, 100, 140 mg/kg (group C) or combination of diclofenac (30 mg/kg, ip) and sunitinib (25, 50, 80, 100, 140 mg/kg po). Diclofenac was administered 15 min before sunitinib, mice were euthanized 4 h post-sunitinib dose, and biomarkers and tissue histopathology were assessed. AST was 92.2 ± 8.0 U/L in group A and 159.7 ± 14.6 U/L in group B (p < 0.05); in group C, it the range was 105.1-152.6 U/L, and in group D, it was 156.0-209.5 U/L (p < 0.05). ALT was 48.9 ± 1.6 U/L (group A), 95.1 ± 4.5 U/L (p < 0.05) in group B, and 50.5-77.5 U/L in group C and 82.3-115.6 U/L after coadministration (p < 0.05). Renal function biomarker BUN was 16.3 ± 0.6 mg/dl (group A) and increased to 29.9 ± 2.6 mg/dl in group B (p < 0.05) and it the range was 19.1-33.3 mg/dl (p < 0.05) and 26.9-40.8 mg/dl in groups C and D, respectively. Creatinine was 5.9 pmol/ml in group A; 6.2 pmol/ml in group B (p < 0.01), and the range was 6.0-6.2 and 6.2-6.4 pmol/ml in groups C and D, respectively (p < 0.05 for D). Histopathological assessment (vascular and inflammation damages) showed toxicity in group B (p < 0.05) and mild toxicity in group C. Damage was significantly lesser in group D than group B (p < 0.05). Spleen only showed toxicity after coadministration. These results suggest vascular and inflammation protective effects of sunitinib, not shown after biomarker analysis.
    Matched MeSH terms: Antineoplastic Agents/administration & dosage*
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