scholarly journals Development of Nanocapsules Containing Cytotoxic Agents- A Review

2021 ◽  
Vol 7 (2) ◽  
pp. 152-167
Author(s):  
Sani Ega Priani ◽  
Tia Nur Setianty ◽  
Ratih Aryani ◽  
Sri Peni Fitrianingsih ◽  
Livia Syafnir
Keyword(s):  
Water Solubility ◽  
Sodium Tripolyphosphate ◽  
Drug Stability ◽  
Particle Surface ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Agents ◽  
Natural Polymers ◽  
Particle Size Reduction ◽  
Incidence And Mortality

Background: The incidence and mortality of cancer are rapidly growing worldwide. Modification on drug delivery systems based on nanotechnology was applied to improve the effectiveness and safety of treatment. Nanoencapsulation, a part of nanotechnology,  was known can be involved in cytotoxic agents. Objective: This research was conducted to determine the type of polymers for nanoencapsulation of cytotoxic agents and analyze the effect of nanoencapsulation on the cytotoxic activity. Methods: The study was performed by systematic literature review using selected articles from reputable databases that meet the inclusion and exclusion criteria. Results: The results show that many cytotoxic agents have been developed in nanocapsules systems due to their low water solubility, chemical instability, and low bioavailability. The nanoencapsulation process was carried out using synthetic or natural polymers such as polylactic-co-glycolic acid (PLGA), PEGylated PLGA, polycaprolactone (PCL), chitosan-sodium tripolyphosphate, chitosan-sodium alginate, heparin-poly(l-lysine), and polymethyl methacrylate (PMMA). Those polymers are widely used for nanoencapsulation related to their biocompatible, biodegradable, non-toxic, and providing the desired coating properties. The nanoencapsulation on cytotoxic agents significantly increases the in vitro cytotoxicity, marked by the decrease of IC50 value in the range 1.4-15.4 folds compared to pure drugs. The increase in cytotoxicity could be caused by particle size reduction, modification of particle surface properties, and enhancement of drug stability. Conclusion: It can be concluded that nanoencapsulation can be applied for cytotoxic agents to increase their activity using the appropriate coating polymer.

scholarly journals Comparative Study of Cigarette Smoke Cytotoxicity Using Two In Vitro Assay Systems

2014 ◽  
Vol 26 (3) ◽  
pp. 98-108
Author(s):  
Toshiro Fukushima ◽  
Hitomi Tanaka ◽  
Takeshi Yamamoto
Keyword(s):  
Cigarette Smoke ◽  
Rank Order ◽  
In Vitro Cytotoxicity ◽  
Water Soluble ◽  
Cytotoxic Agents ◽  
Main Stream ◽  
Total Particulate Matter ◽  
Vitro Assay ◽  
Modes Of Action

SUMMARYThe aim of this study was to compare the results obtained from two in vitro cytotoxicity assays that depend upon different mechanisms/modes of action. The Neutral Red Uptake (NRU) assay is based on endocytotic activity whereas the Water Soluble Tetrazolium Salts (WST-1) assay is based on mitochondrial dehydrogenase activity. Both were investigated in light of their wide use and documented validation. The total particulate matter (TPM) and gas vapor phase (GVP) of main stream smoke derived from Kentucky reference cigarettes 3R4F and 10 test cigarettes made of 100% flue-cured or 100% Burley tobacco were individually applied to the two assays using CHO-K1 cells. In addition, cigarette smoke constituents and known cytotoxic agents, documented to affect specific endpoints, were evaluated within both assays. Although the NRU assay was primarily more sensitive than the WST-1 assay, both assays provided comparable results in terms of the rank order for the cytotoxicity of cigarette smoke samples. In addressing the cytotoxicity of constituents in cigarette smoke, acrolein, hydroquinone and catechol gave clear dose-related decreases in cell viability (an end point common in both assays). Moreover, enzyme inhibitors of the mitochondrial respiratory chain and chemicals causing membrane disruption also showed similar responses regardless of the specific endpoint addressed within the cytotoxicity assay. In conclusion, results from the NRU and WST-1 assay are comparable therefore indicating results were independent of the different assay detection mechanisms/modes of action. [Beitr. Tabakforsch. Int. 26 (2014) 98-108]

The Design and Synthesis of Novel Phenothiazine Derivatives as Potential Cytotoxic Agents

2019 ◽  
Vol 17 (1) ◽  
pp. 57-67
Author(s):  
Yepeng Luan ◽  
Jinyi Liu ◽  
Jianjun Gao ◽  
Jinhua Wang
Keyword(s):  
Cell Lines ◽  
High Efficiency ◽  
Human Cancer ◽  
Human Tumor ◽  
Cytotoxic Agents ◽  
Cancer Drug ◽  
Human Cancer Cell Lines ◽  
Incidence And Mortality ◽  
Anti Cancer

Background: Cancer incidence and mortality have been increasing and cancer is still the leading cause of death all over the world. Despite the enormous progress in cancer treatment, many patients died of ineffective chemotherapy and drug resistance. Therefore, the design and development of anti-cancer drugs with high efficiency and low toxicity is still one of the most challenging tasks. Tricyclic heterocycles, such as phenothiazine, are always important sources of scaffolds for anti-cancer drug discovery. Methods: In this work, ten new urea-containing derivatives of phenothiazine coupled with different kinds of amine motifs at the endpoint through a three carbon long spacer were designed and synthesized. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR and HRMS. All the synthesized compounds were tested for their antitumor activity in vitro against the proliferation of PC-3 cells, and the compounds with best potency entered further cytotoxicity evaluations against other 22 human tumor cell lines. Mechanism was also studied. Results: From all data, it showed that among all 10 target compounds, TTi-2 showed the best effect in inhibiting the proliferation of 23 human cancer cell lines while TTi-2 without obvious inhibitory effect on normal cell. Furthermore, our results also showed that TTi-2 could inhibit migration, invasion and colony formation of MDA-MB-231 cells. Finally, TTi-2 can induce arrest of cell cycle at G0/G1 phase and cell apoptosis by activating the caspase 3 activity. Conclusion: All these results suggested that TTi-2 might be used as a promising lead compound for anticancer drug development.

Glucosylceramide Synthetase Inhibitors Sensitise B-CLL Cells to Cytotoxic Agents without Reversing P-gp Functional Activity.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1181-1181
Author(s):  
Gareth Gerrard ◽  
Terry D. Butters ◽  
Atul B. Mehta ◽  
A. Victor Hoffbrand ◽  
Derryln Hughes ◽  
...  
Keyword(s):  
Cell Line ◽  
Functional Activity ◽  
Mononuclear Cells ◽  
Efflux Pump ◽  
Specific Inhibitor ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Drugs ◽  
Cytotoxic Agents ◽  
Peripheral Blood Mononuclear

Abstract Malignant B-cells from a high proportion of chronic lymphocytic leukaemia (B-CLL) patients over express the multidrug resistance (MDR) -1 gene encoded transmembrane efflux pump P-glycoprotein (P-gp). Inhibition of glucosylceramide synthesis has been shown to correlate with the expression and function of P-gp and sensitise cells to cytotoxic agents. We analysed the ability of glucosylceramide synthetase (GCS) inhibitors N-butyl-deoxygalactonojirimycin (OGB-1, 500μM) and N-nonyl-deoxygalactonojirimycin (OGB-2, 100μM) to sensitise B-CLL cells to conventional cytotoxic drugs 2-chlorodeoxyadenosine (CdA), chlorambucil (Chl) and fludarabine (FdR) using the in vitro cytotoxicity MTT assay. The effect on P-gp activity was also analysed using the calcein-AM accumulation assay and the results expressed as multidrug activity factor (MAF), where a MAF of >10 in the presence of a P-gp inhibitor denotes P-gp functional activity. GCS inhibitors were cultured with B-CLL cells for 24-48h before the assays were performed. The P-gp negative cell line CEM-CCRF had no MAF activity with an IC50 for vincristine (a known P-gp substrate) of <1ng/ml. The P-gp over expressing cell line CEM-VLB showed a MAF value of 96.4 with zosuquidar trihydrochloride (Z.3HCL), a specific inhibitor of P-gp, 15.7 with OGB-1 and 45.9 with OGB-2. The IC50 for vincristine was reduced from >10ug/ml to 55.5ng/ml in the presence of OGB-2. In peripheral blood mononuclear cells from 3 normal volunteers (all P-gp +ve), the mean MAF value for Z.3HCL was 23.86 and for OGB-2 was 16.2. In 9/13 B-CLL samples there was P-gp functional activity in the presence of Z.3HCL with a mean MAF value of 22.15 (range 11.27–37.3). P-gp was over expressed in10/13 B-CLL samples. However, when available samples from this cohort were assessed with OGB-1 (n=4) and OGB-2 (n=13) the MAF value was <10. Nevertheless, sensitisation of B-CLL cells was observed by a reduction in the IC50 in the presence of OGB-1 with CdA in 3/4 (to 40% in the presence of cytotoxic drug alone), Chl in 3/4 (39%), FdR in 2/4 (26%) and in the presence of OGB-2 with CdA in 8/13 (42%), Chl in 5/13 (40%) and FdR in 7/13 (34%). Although GCS inhibitors sensitize B-CLL cells to cytotoxic drugs in some B-CLL patients, they do not appear to have any effect on P-gp functional activity.

scholarly journals Synthesis and In Silico Docking of New Pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine-based Cytotoxic Agents

2021 ◽  
Vol 22 (19) ◽  
pp. 10258
Author(s):  
Mabrouk Horchani ◽  
Niels V. Heise ◽  
Sophie Hoenke ◽  
René Csuk ◽  
Abdel Halim Harrath ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
In Silico ◽  
Human Tumor ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Agents ◽  
Hek293 Cells ◽  
Binding Interaction ◽  
In Silico Docking

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivativeshave been designed and synthesized viacyclocondensation reactions of pyrazolo-enaminone with a series of arylidenemalononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole. The structures of the target compounds were investigated by spectral techniques and elemental analysis (IR, UV–Vis, 1H NMR, 13C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the pyrazolo-pyrido-pyrimidine analog bearing a 4-Br-phenyl moiety was the most active toward many cell lines with EC50 values ranging between 9.1 and 13.5 µM. Moreover, in silico docking studies of the latter with six anticancer drug targets, i.e., DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX5, were also performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.

scholarly journals Formulation and In-Vitro Evaluation of Meloxicam Solid Dispersion using Natural Polymers.

2021 ◽  
Vol 30 (1) ◽  
pp. 169-178
Author(s):  
Hiba Radhi ALhassani ◽  
Eman B. H. Al-Khedairy
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Water Solubility ◽  
Oral Absorption ◽  
Chemical Interaction ◽  
Water Soluble ◽  
Natural Polymers ◽  
Drug Content ◽  
Percentage Yield

Meloxicam (MLX) is non-steroidal anti -inflammatory, poorly water soluble, highly permeable drug and the rate of its oral absorption is often controlled by the dissolution rate in the gastrointestinal tract. Solid dispersion (SD) is an effective technique for enhancing the solubility and dissolution rate of such drug.     The present study aims to enhance the solubility and the dissolution rate of MLX by SD technique by solvent evaporation method using sodium alginate (SA), hyaluronic acid (HA), collagen and xyloglucan (XG) as gastro-protective hydrophilic natural polymers. Twelve formulas were prepared in different drug: polymer ratios and evaluated for their, percentage yield, drug content,  water solubility,  dissolution, crystal lattice using powder X-ray diffraction (PXRD) and studies and Fourier Transform Infrared Spectroscopy (FTIR) for determination the drug-polymer interaction. All the prepared showed improvement of drug solubility except that prepared with HA. The best result was obtained with formula SD1 (MLX: SA 1:1) that showed a high percentage yield (97), high drug content (97.4±0.05) and increase in solubility compared to solubility of pure MLX with improved dissolution rate. the PXRD study revealed the conversion of the drug to amorphous form without chemical interaction according to FTIR results

scholarly journals Synthesis and In Silico Docking of New Pyrazolo[4,3-e]Pyrido[1,2-a]Pyrimidine-Based Cytotoxic Agents

2021 ◽  
Author(s):  
Mabrouk Horchani ◽  
Niels V. Heise ◽  
Sophie Hoenke ◽  
Rene Csuk ◽  
Abdel Halim Harrath ◽  
...  
Keyword(s):  
Cell Lines ◽  
Anticancer Agents ◽  
In Silico ◽  
Human Tumor ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Agents ◽  
Hek293 Cells ◽  
Binding Interaction ◽  
In Silico Docking

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivatives 7a-l have been designed and synthesized via cyclocondensation reactions of pyrazolo-enaminone 5 with a series of arylidene malononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole (3). The structures of the target compounds 7a-l were investigated by spectral techniques and elemental analysis (IR, UV-Vis, 1H NMR, 13C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the conjugate 7e was the most active towards many cell lines with EC50 values ranging between 9.1 and 13.5 µM, respectively. Moreover, in silico docking studies of 7e with six anticancer drug targets, i.e. DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX also was performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.

DEVELOPMENT AND CHARACTERIZATION OF A NANOCARRIER FOR QUERCETIN

2009 ◽  
Vol 08 (01n02) ◽  
pp. 175-179 ◽  
Author(s):  
MAN-YI WONG ◽  
GIGI N. C. CHIU
Keyword(s):  
Breast Cancer Cells ◽  
Water Solubility ◽  
Storage Temperature ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Compound ◽  
Naturally Occurring ◽  
Quercetin Concentration ◽  
Fold Stability

Quercetin is a naturally occurring cytotoxic compound where clinical use has been limited by its low water solubility. Therefore, liposomes were explored for solubilizing quercetin. Liposomes composed of DPPC (1,2 dipalmitoyl-sn-glycerol-3-phosphocholine)/DSPE-PEG2000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)2000])/quercetin (90:5:5 mole ratio) incorporated quercetin efficiently at 100.9 ± 4.6% and increased quercetin concentration in water 11.2-fold. Stability studies at storage temperature of 4°C showed that the liposomes were stable for up to 16 weeks, without any significant changes in diameters. Liposomal quercetin showed a delayed release profile and reduced quercetin degradation. In vitro cytotoxicity tests also showed that the ED50 of liposomal quercetin was 17.6 times lower than free quercetin in MDA-MB-231 breast cancer cells. In conclusion, the DPPC/DSPE-PEG-based liposomes were stable and were capable of solubilizing quercetin, preventing quercetin degradation, and increasing quercetin in vitro cytotoxicity. Hence, liposomes are a suitable nanocarrier for quercetin.

The Syntheses and Medicinal Attributes of Phenanthrenes as Anticancer Agents: A Quinquennial Update

2021 ◽  
Vol 28 ◽  
Author(s):  
Sarthak Jhingran ◽  
Kritika Laxmikeshav ◽  
Sayali Mone ◽  
Venkata Rao K ◽  
Nagula Shankaraiah
Keyword(s):  
Anticancer Agents ◽  
Chemotherapeutic Agents ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Agents ◽  
Base Pairs ◽  
Biological Targets ◽  
Carcinoma Cell Lines ◽  
Dna Base ◽  
Dna Base Pairs

: Cancer is a silent killer and remains to pose major health problems globally. Amongst the several biological targets, DNA is one of the most striking targets in cancer chemotherapy. Owing to its planar structure, phenanthrene and its derivatives exhibit potential cytotoxicity by intercalating between the DNA base pairs and by inhibiting the enzymes that are involved in the synthesis of DNA. However, due to the off-target effects and resistance, the development of novel chemotherapeutic agents would be meritorious. In this regard, we detail in the review on the development of phenanthrene-based derivatives reported in the last quinquennial. This review mainly focuses on the synthetic aspects and strategies to procure the fused phenanthrene derivatives such as (i) phenanthroindolizidines, phenanthroquinolizidine, phenanthroimidazoles, podophyllotoxin-based phenanthrenes and dihydrophenanthrodioxine derivatives, (ii) phenanthrene conjugates with other pharmacologically significant pharmacophores and (iii) phenanthrene-metal complexes. This review also edifies their potential in vitro cytotoxicity evaluation against various carcinoma cell lines in submicromolar to nanomolar ranges. Additionally, computational studies and structure-activity relationships (SARs) have also been presented to highlight the essential features of the designed congeners. Thus, this review would aid in the development of novel derivatives in future as potential cytotoxic agents in the field of medicinal chemistry.

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