Synthesis and in vitro Cytotoxicity Studies of Certain Novel Heterocycles Derived from Bis 1, 2, 4-Triazoles and their DNA Damage Studies

Aims: Here, three liposomal formulations of DPPC/DPPG/Chol/DSPE-mPEG2000 (F1), DPPC/DPPG/Chol (F2) and HSPC/DPPG/Chol/DSPE-mPEG2000 (F3) encapsulating BTZ were prepared and characterized in terms of their size, surface charge, drug loading, and release profile. Mannitol was used as a trapping agent to entrap the BTZ inside the liposomal core. The cytotoxicity and anti-tumor activity of formulations were investigated in vitro and in vivo in mice bearing tumor. Background: Bortezomib (BTZ) is an FDA approved proteasome inhibitor for the treatment of mantle cell lymphoma and multiple myeloma. The low solubility of BTZ has been responsible for the several side effects and low therapeutic efficacy of the drug. Encapsulating BTZ in a nano drug delivery system; helps overcome such issues. Among NDDSs, liposomes are promising diagnostic and therapeutic delivery vehicles in cancer treatment. Objective: Evaluating anti-tumor activity of bortezomib liposomal formulations. Methods: Data prompted us to design and develop three different liposomal formulations of BTZ based on Tm parameter, which determines liposomal stiffness. DPPC (Tm 41°C) and HSPC (Tm 55°C) lipids were chosen as variables associated with liposome rigidity. In vitro cytotoxicity assay was then carried out for the three designed liposomal formulations on C26 and B16F0, which are the colon and melanoma cancer mouse-cell lines, respectively. NIH 3T3 mouse embryonic fibroblast cell line was also used as a normal cell line. The therapeutic efficacy of these formulations was further assessed in mice tumor models. Result: MBTZ were successfully encapsulated into all the three liposomal formulations with a high entrapment efficacy of 60, 64, and 84% for F1, F2, and F3, respectively. The findings showed that liposomes mean particle diameter ranged from 103.4 to 146.8nm. In vitro cytotoxicity studies showed that liposomal-BTZ formulations had higher IC50 value in comparison to free BTZ. F2-liposomes with DPPC, having lower Tm of 41°C, showed much higher anti-tumor efficacy in mice models of C26 and B16F0 tumors compared to F3-HSPC liposomes with a Tm of 55°C. F2 formulation also enhanced mice survival compared with untreated groups, either in BALB/c or in C57BL/6 mice. Conclusion: Our findings indicated that F2-DPPC-liposomal formulations prepared with Tm close to body temperature seem to be effective in reducing the side effects and increasing the therapeutic efficacy of BTZ and merits further investigation.

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Recent Advances in Curcumin Nanocarriers for the Treatment of Different Types of Cancer with Special Emphasis on In Vitro Cytotoxicity and Cellular Uptake Studies

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681209666190417144126 ◽

2020 ◽

Vol 10 (5) ◽

pp. 577-590

Author(s):

Jai B. Sharma ◽

Shailendra Bhatt ◽

Asmita Sharma ◽

Manish Kumar

Keyword(s):

Cancer Cells ◽

Cellular Uptake ◽

Anticancer Agents ◽

Targeted Delivery ◽

In Vitro Cytotoxicity ◽

Curcumin Nanoparticles ◽

Cytotoxicity Studies ◽

Delivery Technique ◽

Different Types

Background: The potential use of nanocarriers is being explored rapidly for the targeted delivery of anticancer agents. Curcumin is a natural polyphenolic compound obtained from rhizomes of turmeric, belongs to family Zingiberaceae. It possesses chemopreventive and chemotherapeutic activity with low toxicity in almost all types of cancer. The low solubility and bioavailability of curcumin make it unable to use for the clinical purpose. The necessity of an effective strategy to overcome the limitations of curcumin is responsible for the development of its nanocarriers. Objective: This study is aimed to review the role of curcumin nanocarriers for the treatment of cancer with special emphasis on cellular uptake and in vitro cytotoxicity studies. In addition to this, the effect of various ligand conjugated curcumin nanoparticles on different types of cancer was also studied. Methods: A systematic review was conducted by extensively surfing the PubMed, science direct and other portals to get the latest update on recent development in nanocarriers of curcumin. Results: The current data from recent studies showed that nanocarriers of curcumin resulted in the targeted delivery, higher efficacy, enhanced bioavailability and lower toxicity. The curcumin nanoparticles showed significant inhibitory effects on cancer cells as compared to free curcumin. Conclusion: It can be concluded that bioavailability of curcumin and its cytotoxic effect to cancer cells can be enhanced by the development of curcumin based nanocarriers and it was found to be a potential drug delivery technique for the treatment of cancer.

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An efficient l-proline catalyzed synthesis of pyrazolo[3,4-e][1,4]thiazepine derivatives and their in vitro cytotoxicity studies

Medicinal Chemistry Research ◽

10.1007/s00044-014-1153-3 ◽

2014 ◽

Vol 24 (2) ◽

pp. 553-562 ◽

Cited By ~ 4

Author(s):

A. Srikanth ◽

S. Sarveswari ◽

V. Vijayakumar ◽

P. Gridharan ◽

S. Karthikeyan

Keyword(s):

In Vitro Cytotoxicity ◽

Cytotoxicity Studies

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Intrathecal Mafosfamide: A Preclinical Pharmacology and Phase I Trial

Journal of Clinical Oncology ◽

10.1200/jco.2005.06.053 ◽

2005 ◽

Vol 23 (7) ◽

pp. 1555-1563 ◽

Cited By ~ 47

Author(s):

Susan M. Blaney ◽

Frank M. Balis ◽

Stacey Berg ◽

Carola A.S. Arndt ◽

Richard Heideman ◽

...

Keyword(s):

Phase I ◽

Phase Ii ◽

Phase I Trial ◽

Neoplastic Meningitis ◽

In Vitro Cytotoxicity ◽

Pharmacokinetic Studies ◽

Preclinical Studies ◽

Phase Ii Trials ◽

Cytotoxicity Studies

Purpose Preclinical studies of mafosfamide, a preactivated cyclophosphamide analog, were performed to define a tolerable and potentially active target concentration for intrathecal (IT) administration. A phase I and pharmacokinetic study of IT mafosfamide was performed to determine a dose for subsequent phase II trials. Patients and Methods In vitro cytotoxicity studies were performed in MCF-7, Molt-4, and rhabdomyosarcoma cell lines. Feasibility and pharmacokinetic studies were performed in nonhuman primates. These preclinical studies were followed by a phase I trial in patients with neoplastic meningitis. There were five dose levels ranging from 1 mg to 6.5 mg. Serial CSF samples were obtained for pharmacokinetic studies in a subset of patients with Ommaya reservoirs. Results The cytotoxic target exposure for mafosfamide was 10 μmol/L. Preclinical studies demonstrated that this concentration could be easily achieved in ventricular CSF after intraventricular dosing. In the phase I clinical trial, headache was the dose-limiting toxicity. Headache was ameliorated at 5 mg by prolonging the infusion rate to 20 minutes, but dose-limiting headache occurred at 6.5 mg dose with prolonged infusion. Ventricular CSF mafosfamide concentrations at 5 mg exceeded target cytotoxic concentrations after an intraventricular dose, but lumbar CSF concentrations 2 hours after the dose were less than 10 μmol/L. Therefore, a strategy to alternate dosing between the intralumbar and intraventricular routes was tested. Seven of 30 registrants who were assessable for response had a partial response, and six had stable disease. Conclusion The recommended phase II dose for IT mafosfamide, administered without concomitant analgesia, is 5 mg over 20 minutes.

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In-vitro cytotoxicity, antioxidant, bleomycin-dependent DNA damage and immunomodulatory evaluation of 1-(4-acetylphenyl)-3-aryloxypyrrolidine-2, 5-dione based derivatives

Medicinal Chemistry Research ◽

10.1007/s00044-014-0965-5 ◽

2014 ◽

Vol 23 (8) ◽

pp. 3907-3915 ◽

Cited By ~ 6

Author(s):

Jigarkumar R. Patel ◽

Bhaveshkumar D. Dhorajiya ◽

Bharatkumar Z. Dholakiya ◽

Farid A. Badria ◽

Ahmed S. Ibrahim

Keyword(s):

Dna Damage ◽

In Vitro Cytotoxicity

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Polymeric/Inorganic Multifunctional Nanoparticles for Simultaneous Drug Delivery and Visualization

MRS Proceedings ◽

10.1557/proc-1257-o04-03 ◽

2010 ◽

Vol 1257 ◽

Cited By ~ 2

Author(s):

Andrea Fornara ◽

Alberto Recalenda ◽

Jian Qin ◽

Abhilash Sugunan ◽

Fei Ye ◽

...

Keyword(s):

Drug Delivery ◽

Fluorescence Microscopy ◽

Contrast Agents ◽

Gold Nanorods ◽

In Vitro Cytotoxicity ◽

In Vivo Studies ◽

Multifunctional Nanoparticles ◽

Cytotoxicity Studies

AbstractNanoparticles consisting of different biocompatible materials are attracting a lot of interest in the biomedical area as useful tools for drug delivery, photo-therapy and contrast enhancement agents in MRI, fluorescence and confocal microscopy. This work mainly focuses on the synthesis of polymeric/inorganic multifunctional nanoparticles (PIMN) based on biocompatible di-block copolymer poly(L,L-lactide-co-ethylene glycol) (PLLA-PEG) via an emulsion-evaporation method. Besides containing a hydrophobic drug (Indomethacin), these polymeric nanoparticles incorporate different visualization agents such as superparamagnetic iron oxide nanoparticles (SPION) and fluorescent Quantum Dots (QDs) that are used as contrast agents for Magnetic Resonance Imaging (MRI) and fluorescence microscopy together. Gold Nanorods are also incorporated in such nanostructures to allow simultaneous visualization and photodynamic therapy. MRI studies are performed with different loading of SPION into PIMN, showing an enhancement in T2 contrast superior to commercial contrast agents. Core-shell QDs absorption and emission spectra are recorded before and after their loading into PIMN. With these polymeric/inorganic multifunctional nanoparticles, both MRI visualization and confocal fluorescence microscopy studies can be performed. Gold nanorods are also synthesized and incorporated into PIMN without changing their longitudinal absorption peak usable for lased excitation and phototherapy. In-vitro cytotoxicity studies have also been performed to confirm the low cytotoxicity of PIMN for further in-vivo studies.

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Serotherapy of B-cell neoplasms with anti-B4-blocked ricin: a phase I trial of daily bolus infusion

Blood ◽

10.1182/blood.v79.3.576.bloodjournal793576 ◽

1992 ◽

Vol 79 (3) ◽

pp. 576-585 ◽

Cited By ~ 1

Author(s):

ML Grossbard ◽

AS Freedman ◽

J Ritz ◽

F Coral ◽

VS Goldmacher ◽

...

Keyword(s):

Phase I ◽

B Cell ◽

Maximum Tolerated Dose ◽

In Vitro Cytotoxicity ◽

Bolus Infusion ◽

Protein Toxin ◽

Cytotoxicity Studies ◽

Ricin A

Anti-B4-blocked Ricin (Anti-B4-bR) is an immunotoxin comprised of the anti-B4 monoclonal antibody (MoAb) and the protein toxin “blocked ricin.” The anti-B4 MoAb is directed against the B-lineage-restricted CD19 antigen expressed on more than 95% of normal and neoplastic B cells. Blocked ricin is an altered ricin derivative that has its nonspecific binding eliminated by chemically blocking the galactose binding domains of the B chain. In vitro cytotoxicity studies demonstrate that the IC37 of Anti-B4-bR is 2 x 10(-11) mol/L compared with 4 x 10(-12) mol/L for native ricin. A phase I dose escalation clinical trial was conducted in 25 patients with refractory B-cell malignancies. Anti-B4-bR was administered by daily 1-hour bolus infusion for 5 consecutive days at doses ranging from 1 microgram/kg/d to 60 micrograms/kg/d. Serum levels above 1 nmol/L were achieved transiently in the majority of patients treated at the maximum tolerated dose of 50 micrograms/kg/d for 5 days for a total dose of 250 micrograms/kg. The dose-limiting toxicity was defined by transient, reversible grade 3 elevations in hepatic transaminases, without impaired hepatic synthetic function. Minor toxicities included transient hypoalbuminemia, thrombocytopenia, and fevers. Human antimouse antibody and human anti-ricin antibody were detected in nine patients. One complete response, two partial responses, and eight mixed or transient responses were observed. These results show the in vitro and in vivo cytotoxicity of Anti-B4-bR and indicate that this immunotoxin can be administered as a daily bolus infusion for 5 days with tolerable, reversible toxicity.

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Development, Characterization and In Vitro Evaluation of Paclitaxel and Anastrozole Co-Loaded Liposome

Processes ◽

10.3390/pr8091110 ◽

2020 ◽

Vol 8 (9) ◽

pp. 1110

Author(s):

Minh Thanh Vu ◽

Dinh Tien Dung Nguyen ◽

Ngoc Hoi Nguyen ◽

Van Thu Le ◽

The Nam Dao ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Combination Therapy ◽

Cancer Treatment ◽

Cancer Cells ◽

Breast Cancer Treatment ◽

In Vitro Cytotoxicity ◽

Cytotoxicity Studies ◽

Combined Drugs

Paclitaxel (PTX) and anastrozole (ANA) have been frequently applied in breast cancer treatment. PTX is well-known for its anti-proliferative effect meanwhile ANA has just been discovered to act as an estrogen receptor α (ERα) ligand. The combination therapy of PTX and ANA is expected to improve treating efficiency, as ANA would act as a ligand binding with the ERα gene expressed in breast cancer cells and thereafter PTX would inhibit the division and cause death to those cancer cells. In this study, liposome-based nanocarriers (LP) were developed for co-encapsulation of PTX and ANA to improve the efficacy of the combined drugs in an Estrogen receptor-responsive breast cancer study. PTX-ANA co-loaded LP was prepared using thin lipid film hydration method and was characterized for morphology, size, zeta potential, drug encapsulation and in vitro drug release. In addition, cell proliferation (WST assay) and IN Cell Analyzer were used for in vitro cytotoxicity studies on a human breast cancer cell line (MCF-7). Results showed that the prepared LP and PTX-ANA-LP had spherical vesicles, with a mean particle size of 170.1 ± 13.5 nm and 189.0 ± 22.1 nm, respectively. Controlled and sustained releases were achieved at 72 h for both of the loaded drugs. The in vitro cytotoxicity study found that the combined drugs showed higher toxicity than each single drug separately. These results suggested a new approach to breast cancer treatment, consisting of the combination therapy of PTX and ANA in liposomes based on ER response.

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