The Effect of Phase Transition Temperature on Therapeutic Efficacy of Liposomal Bortezomib

2020 ◽  
Vol 20 (6) ◽  
pp. 700-708
Author(s):  
Mitra Korani ◽  
Sara Nikoofal-Sahlabadi ◽  
Amin R. Nikpoor ◽  
Solmaz Ghaffari ◽  
Hossein Attar ◽  
...  
Keyword(s):  
Side Effects ◽  
Cell Line ◽  
Therapeutic Efficacy ◽  
Drug Loading ◽  
Particle Diameter ◽  
In Vitro Cytotoxicity ◽  
Liposomal Formulations ◽  
Cytotoxicity Studies ◽  
Anti Tumor Activity

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.

scholarly journals Sustained Release and Cytotoxicity Evaluation of Carbon Nanotube-Mediated Drug Delivery System for Betulinic Acid

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Julia M. Tan ◽  
Govindarajan Karthivashan ◽  
Palanisamy Arulselvan ◽  
Sharida Fakurazi ◽  
Mohd Zobir Hussein
Keyword(s):  
Carbon Nanotubes ◽  
Cell Line ◽  
Drug Carrier ◽  
Drug Loading ◽  
Fibroblast Cell ◽  
Xrd Analysis ◽  
Prolonged Release ◽  
Loading Capacity ◽  
Cytotoxicity Studies

Carbon nanotubes (CNTs) have been widely utilized as a novel drug carrier with promising future applications in biomedical therapies due to their distinct characteristics. In the present work, carboxylic acid-functionalized single-walled carbon nanotubes (f-SWCNTs) were used as the starting material to react with anticancer drug, BA to produce f-SWCNTs-BA conjugate viaπ-πstacking interaction. The conjugate was extensively characterized for drug loading capacity, physicochemical properties, surface morphology, drug releasing characteristics, and cytotoxicity evaluation. The results indicated that the drug loading capacity was determined to be around 20 wt% and this value has been verified by thermogravimetric analysis. The binding of BA onto the surface of f-SWCNTs was confirmed by FTIR and Raman spectroscopies. Powder XRD analysis showed that the structure of the conjugate was unaffected by the loading of BA. The developed conjugate was found to release the drug in a controlled manner with a prolonged release property. According to the preliminaryin vitrocytotoxicity studies, the conjugate was not toxic in a standard fibroblast cell line, and anticancer activity was significantly higher in A549 than HepG2 cell line. This study suggests that f-SWCNTs could be developed as an efficient drug carrier to conjugate drugs for pharmaceutical applications in cancer chemotherapies.

scholarly journals CARMUSTINE LOADED NANOSIZE LIPID VESICLES SHOWED PREFERENTIAL CYTOTOXICITY AND INTERNALIZATION IN U87MG CELL LINE ALONG WITH IMPROVED PHARMACOKINETIC PROFILE IN MICE: A STRATEGY FOR TREATMENT OF GLIOMA

2020 ◽  
pp. 240-248
Author(s):  
BHABANI SANKAR SATAPATHY ◽  
JNANRANJAN PANDA
Keyword(s):  
Electron Microscopy ◽  
Cell Line ◽  
Drug Loading ◽  
Lipid Vesicles ◽  
Pharmacokinetic Profile ◽  
In Vitro Cytotoxicity ◽  
Pharmacokinetic Data ◽  
Transmission Electron

Objective: Successful treatment of glioma still remains a tough challenge. The present study aims at the development and evaluation of carmustine loaded nanosize phospholipid vesicles (CNLVs) for the treatment of glioma. Methods: The experimental NLVs were developed by conventional lipid layer hydration technique and were characterized by different in vitro tools such as diffraction light scattering (DLS), zeta potential, field emission scanning electron microscopy (FESEM), cryo-transmission electron microscopy (cryo-TEM), in vitro drug loading capacity, drug release study etc. In vitro cytotoxicity and cellular uptake of the optimized drug-loaded NLVs were carried out in U87MG human glioblastoma cell line. In vivo pharmacokinetic study was conducted in Swiss albino mice. Results: DLS data showed an average vesicle diameter of 92 nm with narrow size distribution. Optimized CNLVs were spherical in shape with a smooth surface as depicted from FESEM data. Cryo-TEM study confirmed formation of unilamellar vesicles with intact outer bilayer. A reasonable drug loading of 7.8 % was reported for the optimized CNLVs along with a sustained release of CS over a 48 h study period. In vitro cytotoxicity assay revealed a considerable higher toxicity of CNLVs than free drugs in the U87MG cells. Confocal microscopy showed a satisfactory internalization of the optimized drug-loaded NLVs in the tested cell line. Pharmacokinetic data demonstrated an enhanced mean residence time of optimized CNLVs in blood than free drug. Conclusion: Results depicted the potential of experimental CNLVs for the treatment of glioma after further in vivo tests.

scholarly journals Preparation, Optimization and In-Vitro Evaluation of Curcumin-Loaded Niosome@calcium Alginate Nanocarrier as a New Approach for Breast Cancer Treatment

Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 173
Author(s):  
Iman Akbarzadeh ◽  
Mona Shayan ◽  
Mahsa Bourbour ◽  
Maryam Moghtaderi ◽  
Hassan Noorbazargan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Cancer Cells ◽  
Calcium Alginate ◽  
Drug Loading ◽  
Cytotoxicity Studies ◽  
Significant Release ◽  
Gene Expression Studies ◽  
Mcf10a Cells

Cancer is one of the most common causes of mortality, and its various treatment methods can have many challenges for patients. As one of the most widely used cancer treatments, chemotherapy may result in diverse side effects. The lack of targeted drug delivery to tumor tissues can raise the possibility of damage to healthy tissues, with attendant dysfunction. In the present study, an optimum formulation of curcumin-loaded niosomes with a calcium alginate shell (AL-NioC) was developed and optimized by a three-level Box–Behnken design—in terms of dimension and drug loading efficiency. The niosomes were characterized by transmission electron microscopy, Fourier-transform infrared spectroscopy, and dynamic light scattering. The as-formulated niosomes showed excellent stability for up to 1 month at 4 °C. Additionally, the niosomal formulation demonstrated a pH-dependent release; a slow-release profile in physiological pH (7.4), and a more significant release rate at acidic conditions (pH = 3). Cytotoxicity studies showed high compatibility of AL-NioC toward normal MCF10A cells, while significant toxicity was observed in MDA-MB-231 and SKBR3 breast cancer cells. Gene expression studies of the cancer cells showed downregulation of Bcl2, cyclin D, and cyclin E genes, as well as upregulation of P53, Bax, caspase-3, and caspase-9 genes expression following the designed treatment. Flow cytometry studies confirmed a significant enhancement in the apoptosis rate in the presence of AL-NioC in both MDA-MB-231 and SKBR3 cells as compared to other samples. In general, the results of this study demonstrated that—thanks to its biocompatibility toward normal cells—the AL-NioC formulation can efficiently deliver hydrophobic drugs to target cancer cells while reducing side effects.

Formulation and Optimization of Paclitaxel Loaded Lipid Nanoparticles and Their In Vitro Cytotoxicity Studies Using H1299 Lung Cancer Cell Lines

2019 ◽  
Vol 11 (12) ◽  
pp. 1202-1217 ◽  
Author(s):  
Hiren Khatri ◽  
Nimitt Chokshi ◽  
Shruti Rawal ◽  
Bhoomika Patel ◽  
Mayur M. Patel
Keyword(s):  
Lung Cancer ◽  
Particle Size ◽  
Cell Lines ◽  
Release Kinetics ◽  
Drug Loading ◽  
Lipid Nanoparticles ◽  
In Vitro Cytotoxicity ◽  
H1299 Cell ◽  
Cytotoxicity Studies

Lung cancer is the leading cause of cancer-related death in the world, and approximately 80% to 85% of lung cancers are non-small cell lung cancer (NSCLC). Paclitaxel (PTX) has been widely used for the treatment of NSCLC. It is classified as a BCS class IV drug and offers a low therapeutic index. The present investigation demonstrates development of orally administered PEGylated, PTX loaded solid lipid nanoparticles (PTX-SLNs). A Box-Behnken design was applied to systematically optimize PTX-SLNs. Drug concentration, emulsifier concentration and homogenization pressure were selected as an independent variables, and particle size, % entrapment efficiency (%EE) and % drug loading (%DL) were selected as dependent variables. The particle size of optimized PTXSLNs was found to be 401 ± 12 nm, with %EE of 86.63 ± 2.58%, and %DL of 7.42 ± 0.11%. The developed PTX-SLNs exhibited anti-lipolytic effect due to its stabilization by MPEG2000-DSPE. Moreover, the in vitro GI stability studies revealed good stability of PTX-SLNs in various GI tract media. The in vitro drug release studies revealed controlled release profile with Weibull model release kinetics. In vitro cytotoxicity studies in H1299 cell lines revealed significant decline in IC50 values of PTX-SLNs treated cells as compared to pure drug, thus revealing an improved efficacy of the developed systems.

scholarly journals In Vitro Cytotoxicity of Some Natural and Semi-Synthetic Isocoumarins from Paepalanthus bromelioides

2002 ◽  
Vol 57 (1-2) ◽  
pp. 85-88 ◽  
Author(s):  
Karina F. Devienne ◽  
Maria Stella G. Raddi ◽  
Eliana A. Varanda ◽  
Wagner Vilegas
Keyword(s):  
Antimicrobial Activity ◽  
Side Effects ◽  
Cell Line ◽  
Structural Parameters ◽  
Neutral Red ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Effects ◽  
Neutral Red Assay ◽  
Chemically Modified

Numerous natural compounds have a potential for therapeutic applications, but may have to be chemically modified to alter toxic side effects. We investigated structural parameters that could affect the cytotoxicity of isocoumarins similar to 9,10-dihydroxy-5,7-dimethoxy- 1H-naphtho(2,3c)pyran-1-one (paepalantine 1). Paepalantine 1 has antimicrobial activity, as well as significant in vitro cytotoxic effects in the McCoy cell line. Two other natural and two semi-synthetic isocoumarins with similar structures obtained from the capitula of Paepalanthus bromelioides were tested on the same cell line by the neutral red assay. Substitution of the 9 and/or 10-OH group made these compounds less cytotoxic.

Development of pH-Dependent Nanospheres for Nebulisation- In vitro Diffusion, Aerodynamic and Cytotoxicity Studies

Drug Research ◽  
2018 ◽  
Vol 68 (12) ◽  
pp. 680-686 ◽  
Author(s):  
Pradum Ige ◽  
Sagar Pardeshi ◽  
Raju Sonawane
Keyword(s):  
Particle Size ◽  
Beclomethasone Dipropionate ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
In Vitro Cytotoxicity ◽  
Mean Particle Size ◽  
Cytotoxicity Studies ◽  
In Vitro Diffusion ◽  
Ph Dependent

AbstractThe aim of this work was to evaluate the in vitro performance of nebulized nanosuspension formulation when nebulized using ultrasonic nebulizer. The present investigation deals with successful formulation of Beclomethasone dipropionate loaded HPMCP nanospheres prepared by solvent evaporation technique using PEG 400 as a stabilizer. Beclomethasone dipropionate is a water insoluble drug molecule was encapsulated in HPMCP nanospheres to have pH dependent solubility at basic pH for targeted drug delivery in lung and studied for in vitro cytotoxicity and immediate release capability. The synthesized nanospheres were characterized through drug excipient compatibility, surface topography; mean particle size , zeta potential, PDI, entrapment efficiency and drug loading, in vitro diffusion, aerodynamic, in vitro cytotoxicity and stability studies. The mean particle size and PDI of the optimized batch (F1) had 197.6±0.40 nm and 0.324 ±0.35, respectively. The % entrapment efficiency and % drug loading was found to be 86.56±1.32 and 8.30±0.27, respectively. The optimized batch F1 showed % cumulative drug release 94.77±0.24 at 1 h. The formulation showed cell viability up to 91.28%. It can be concluded that, Beclomethasone dipropionate loaded HPMCP nanospheres was found to be safe, stable with significant increase in solubility and bypass the liver.

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Akhlesh Kumar Jain ◽  
Hitesh Sahu ◽  
Keerti Mishra ◽  
Suresh Thareja
Keyword(s):  
Side Effects ◽  
Liver Cancer ◽  
Entrapment Efficiency ◽  
Xrd Analysis ◽  
In Vitro Cytotoxicity ◽  
Physical Interaction ◽  
Scanning Calorimetry ◽  
Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

5-Nitro-Thiophene-Thiosemicarbazone Derivatives Present Antitumor Activity Mediated by Apoptosis and DNA Intercalation

2019 ◽  
Vol 19 (13) ◽  
pp. 1075-1091 ◽  
Author(s):  
Karla Mirella Roque Marques ◽  
Maria Rodrigues do Desterro ◽  
Sandrine Maria de Arruda ◽  
Luiz Nascimento de Araújo Neto ◽  
Maria do Carmo Alves de Lima ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Antitumor Activity ◽  
Cell Line ◽  
Mitochondrial Membrane ◽  
In Vitro Cytotoxicity ◽  
Dna Intercalation ◽  
Phase Cell ◽  
Fluorescence Studies ◽  
In Silico Studies

Background: Considering the need for the development of new antitumor drugs, associated with the great antitumor potential of thiophene and thiosemicarbazonic derivatives, in this work we promote molecular hybridization approach to synthesize new compounds with increased anticancer activity. Objective: Investigate the antitumor activity and their likely mechanisms of action of a series of N-substituted 2-(5-nitro-thiophene)-thiosemicarbazone derivatives. Methods: Methods were performed in vitro (cytotoxicity, cell cycle progression, morphological analysis, mitochondrial membrane potential evaluation and topoisomerase assay), spectroscopic (DNA interaction studies), and in silico studies (docking and molecular modelling). Results: Most of the compounds presented significant inhibitory activity; the NCIH-292 cell line was the most resistant, and the HL-60 cell line was the most sensitive. The most promising compound was LNN-05 with IC50 values ranging from 0.5 to 1.9 µg.mL-1. The in vitro studies revealed that LNN-05 was able to depolarize (dose-dependently) the mitochondrial membrane, induceG1 phase cell cycle arrest noticeably, promote morphological cell changes associated with apoptosis in chronic human myelocytic leukaemia (K-562) cells, and presented no topoisomerase II inhibition. Spectroscopic UV-vis and molecular fluorescence studies showed that LNN compounds interact with ctDNA forming supramolecular complexes. Intercalation between nitrogenous bases was revealed through KI quenching and competitive ethidium bromide assays. Docking and Molecular Dynamics suggested that 5-nitro-thiophene-thiosemicarbazone compounds interact against the larger DNA groove, and corroborating the spectroscopic results, may assume an intercalating interaction mode. Conclusion: Our findings highlight 5-nitro-thiophene-thiosemicarbazone derivatives, especially LNN-05, as a promising new class of compounds for further studies to provide new anticancer therapies.

Sign in / Sign up

Export Citation Format

Share Document