Combination of Curcumin and Paclitaxel Liposomes Exhibits Enhanced Cytotoxicity Towards A549/A549-T Cells and Unaltered Pharmacokinetics

2020 ◽  
Vol 16 (8) ◽  
pp. 1304-1313
Author(s):  
Xianhu Feng ◽  
Chao Pi ◽  
Shaozhi Fu ◽  
Hongru Yang ◽  
Xiaoli Zheng ◽  
...  
Keyword(s):  
Particle Size ◽  
T Cells ◽  
Free Drug ◽  
Individual Treatment ◽  
Herbal Drugs ◽  
Solvent Evaporation Method ◽  
Combination Treatments ◽  
Promising Strategy ◽  
Uniform Particle Size ◽  
Negative Zeta Potential

Background: Combination chemotherapy of chemo-drugs and natural herbal drugs has been shown to be more advantageous than individual treatment with respect to enhancing cytotoxicity, alleviating toxicity and controlling the development of multidrug resistance (MDR). Purpose: The goal of this study is to construct a combined drug delivery system of curcumin liposomes (CUR-LPs) and paclitaxel liposomes (PTX-LPs) to enhance the anticancer activity and reverse the MDR of PTX. Methods: CUR-LPs and PTX-LPs were prepared by solvent evaporation method with optimal formulation composition. MTT assay was used to assess the effect of the combination of CUR-LPs and PTX-LPs treatments on the proliferation of A549/A549-T cells. In addition, the pharmacokinetic behaviors of the combination treatments were evaluated by HPLC. Results : The mixed liposomes were found to have negative zeta-potential (–17.91 ± 1.21 mV) and relatively uniform particle size (105.88 ± 3.19 nm) with a low polydispersity index (0.21 ± 0.016). IC50 of PTX for combination of CUR-LPs and PTX-LPs decreased in the range of 1.47–2.9 times and 1.59–2.5 times compared to the free-drug counterparts in A549 and A549-T cells, respectively. Superior cytotoxicity and higher synergy (CI< 0.4) were observed for the combination treatment with ratio of 40:1 (CUR-LPs:PTX-LPs) compared with the free-drug counterparts in both cell lines tested. Following intravenous administration in rats, liposomes presented higher bioavailability (CUR-LPs: 9.02 fold; PTX-LPs: 7.32 fold) compared to free drugs. Co-administration did not alter the respective pharmacokinetic behaviors. Conclusion: Overall, the present study presents a promising strategy for the development of compound formulations of CUR and PTX.

Field Efficiency of Certain Biopesticides and Neem Products Against Helicoverpa armigera (Hubner) on Chickpea (Cicer arietinumL.)

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Nihad H. Mutlag ◽  
Ameer S. A. Al-Haddad
Keyword(s):  
Helicoverpa Armigera ◽  
Block Design ◽  
Individual Treatment ◽  
Neem Oil ◽  
Larval Population ◽  
Neem Cake ◽  
Combination Treatments ◽  
Randomized Block Design ◽  
Helicoverpa Armígera ◽  
Nuclear Polyhedrosis

A field study was conducted to evaluate the efficiency of four microbial insecticides viz. Beauveria bassiana; HaNPV (Helicoverpa armigera Nuclear Polyhedrosis virus); (Bacillus thuringiensisvar.kurstaki 2 gm/L); HaNPV+Bt; neem oil; neem cake and D.D.V.P EC 76% @0.05% at Research Farm SHIATS,Allahabad during rabi season of 2011-2012. The experiment was laid out in randomized block design with seven treatment and replicated thrice. The observation larval populations of H. armigera were recorded one day before treatment was recorded at 3,7, and 10 days after treatments. The larva population of H. armigera appeared in the third week of February (8 the Standard week) and reached its peak of 14.65 larvae in first week of April and decline rapidly with maturation of crop. There was only one peak in the larval population observation in the 1st week. Bacillus thuringiensis was the most effective chemical by D.D.V.P.76%@0.05% . Among the microbial insecticides. HaNPV ,was the most effective followed by HaNPV+Bt and neem cake . The combination treatments were less effective than the individual treatment neem oil and B. bassiana were the least effective treatment in reducing the larval population of Heliverpa armigera.

scholarly journals Development and Stability Studies of Novel Liposomal Vancomycin Formulations

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Krishna Muppidi ◽  
Andrew S. Pumerantz ◽  
Jeffrey Wang ◽  
Guru Betageri
Keyword(s):  
Particle Size ◽  
Encapsulation Efficiency ◽  
Antimicrobial Agents ◽  
Preparation Method ◽  
Physical Stability ◽  
Liposomal Formulations ◽  
Promising Strategy ◽  
Activity Variable ◽  
Distribution Studies

A promising strategy to improve the therapeutic efficiency of antimicrobial agents is targeted therapy. Although vancomycin has been considered a gold standard for the therapy of MRSA pneumonia, clinical failure rates have also been reported owing to its slow, time-dependent bactericidal activity, variable lung tissue penetration and poor intracellular penetration into macrophages. Liposomal encapsulation has been established as an alternative for antimicrobial delivery to infected tissue macrophages and offers enhanced pharmacodynamics, pharmacokinetics and decreased toxicity compared to standard preparations. The aim of the present work is to prepare vancomycin in two different liposomal formulations, conventional and PEGylated liposomes using different methods. The prepared formulations were optimized for their particle size, encapsulation efficiency and physical stability. The dehydration-rehydration was found to be the best preparation method. Both the conventional and PEGylated liposomal formulations were successfully formulated with a narrow particle size and size distribution and % encapsulation efficiency of and , respectively. Both the formulations were stable at C for 3 months. These formulations were successfully used to evaluate for their intracellular killing of MRSA and in vivo pharmacokinetic and bio-distribution studies.

scholarly journals Targeting regulatory T cells for immunotherapy in melanoma

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Lili Huang ◽  
Yeye Guo ◽  
Shujing Liu ◽  
Huaishan Wang ◽  
Jinjin Zhu ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
Immune Responses ◽  
Immune Cells ◽  
Therapeutic Efficacy ◽  
Patient Survival ◽  
Therapeutic Antibodies ◽  
Promising Strategy ◽  
Fine Tune

AbstractRegulatory T cells (Tregs) are essential in the maintenance of immunity, and they are also a key to immune suppressive microenvironment in solid tumors. Many studies have revealed the biology of Tregs in various human pathologies. Here we review recent understandings of the immunophenotypes and suppressive functions of Tregs in melanoma, including Treg recruitment and expansion in a tumor. Tregs are frequently accumulated in melanoma and the ratio of CD8+ T cells versus Tregs in the melanoma is predictive for patient survival. Hence, depletion of Tregs is a promising strategy for the enhancement of anti-melanoma immunity. Many recent studies are aimed to target Tregs in melanoma. Distinguishing Tregs from other immune cells and understanding the function of different subsets of Tregs may contribute to better therapeutic efficacy. Depletion of functional Tregs from the tumor microenvironment has been tested to induce clinically relevant immune responses against melanomas. However, the lack of Treg specific therapeutic antibodies or Treg specific depleting strategies is a big hurdle that is yet to be overcome. Additional studies to fine-tune currently available therapies and more agents that specifically and selectively target tumor infiltrating Tregs in melanoma are urgently needed.

scholarly journals Engineering of Lactobacillus jensenii To Secrete RANTES and a CCR5 Antagonist Analogue as Live HIV-1 Blockers

2010 ◽  
Vol 54 (7) ◽  
pp. 2994-3001 ◽  
Author(s):  
Luca Vangelista ◽  
Massimiliano Secchi ◽  
Xiaowen Liu ◽  
Angela Bachi ◽  
Letong Jia ◽  
...  
Keyword(s):  
T Cells ◽  
Sexual Transmission ◽  
Ccr5 Antagonist ◽  
Strong Activity ◽  
Promising Strategy ◽  
Lactobacillus Jensenii ◽  
Proinflammatory Activity ◽  
Anti Hiv ◽  
Hiv 1 ◽  
Prevention Of Hiv

ABSTRACT The development of effective microbicides for the prevention of HIV-1 sexual transmission represents a primary goal for the control of AIDS epidemics worldwide. A promising strategy is the use of bacteria belonging to the vaginal microbiota as live microbicides for the topical production of HIV-1 inhibitors. We have engineered a human vaginal isolate of Lactobacillus jensenii to secrete the anti-HIV-1 chemokine RANTES, as well as C1C5 RANTES, a mutated analogue that acts as a CCR5 antagonist and therefore is devoid of proinflammatory activity. Full-length wild-type RANTES and C1C5 RANTES secreted by L. jensenii were purified to homogeneity and shown to adopt a correctly folded conformation. Both RANTES variants were shown to inhibit HIV-1 infection in CD4+ T cells and macrophages, displaying strong activity against HIV-1 isolates of different genetic subtypes. This work provides proof of principle for the use of L. jensenii-produced C1C5 RANTES to block HIV-1 infection of CD4+ T cells and macrophages, setting the basis for the development of a live anti-HIV-1 microbicide targeting CCR5 in an antagonistic manner.

scholarly journals CRISPR-Cas, a robust gene-editing technology in the era of modern cancer immunotherapy

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Seyed Mohammad Miri ◽  
Elham Tafsiri ◽  
William Chi Shing Cho ◽  
Amir Ghaemi
Keyword(s):  
T Cells ◽  
Cancer Immunotherapy ◽  
Gene Editing ◽  
Genome Engineering ◽  
Building Blocks ◽  
Cell Receptor ◽  
Adoptive Cell Transfer ◽  
Promising Strategy ◽  
Pre Treatment ◽  
Cas A

Abstract Cancer immunotherapy has been emerged as a promising strategy for treatment of a broad spectrum of malignancies ranging from hematological to solid tumors. One of the principal approaches of cancer immunotherapy is transfer of natural or engineered tumor-specific T-cells into patients, a so called “adoptive cell transfer”, or ACT, process. Construction of allogeneic T-cells is dependent on the employment of a gene-editing tool to modify donor-extracted T-cells and prepare them to specifically act against tumor cells with enhanced function and durability and least side-effects. In this context, CRISPR technology can be used to produce universal T-cells, equipped with recombinant T cell receptor (TCR) or chimeric antigen receptor (CAR), through multiplex genome engineering using Cas nucleases. The robust potential of CRISPR-Cas in preparing the building blocks of ACT immunotherapy has broaden the application of such therapies and some of them have gotten FDA approvals. Here, we have collected the last investigations in the field of immuno-oncology conducted in partnership with CRISPR technology. In addition, studies that have addressed the challenges in the path of CRISPR-mediated cancer immunotherapy, as well as pre-treatment applications of CRISPR-Cas have been mentioned in detail.

The Development and Evaluation of a Four-roller Flour Mill with Parallelogram Configuration

2007 ◽  
Vol 3 (6) ◽  
Author(s):  
John Alaba Victor Famurewa
Keyword(s):  
Particle Size ◽  
Opposite Direction ◽  
Size Reduction ◽  
Sieve Analysis ◽  
Feeding Problems ◽  
Roller Mill ◽  
Flour Mill ◽  
Wide Gap ◽  
Uniform Particle Size ◽  
Milled Product

A roller mill was designed and evaluated using four equal size cylindrical rollers with their centers on vertices of a parallelogram. The relative speeds and opposite direction of rotation of the rollers allowed the discharge of the materials on them, and splitting took place in between the first pair of corrugated rollers. The broken seeds were directed towards the second and third nips where adequate size reduction was accomplished consecutively by smooth rollers. The milled products were separated into three fractions: chaff, flour and size larger than flour. The chaff and the flour are collected at different outlets, while the particles with sizes larger than flour are blown back into the hopper for further reduction. The mill was evaluated using three grains: maize, beans and soy beans at different combinations of evaluating parameters. The machine was able to mill grains to flour size without any leakage at the nip points. For all the grains, a wide gap set produced higher throughput than narrow, as well as fast feeding in smaller particle size and higher throughput. The results obtained from the evaluation showed that the machine is very capable of three-stage size reduction to produce flour, avoiding the feeding problems in three high roller mills. Sieve analysis of the milled product for each experiment showed uniform particle size.

Modulation of the central memory and Tr1-like regulatory T cells in multiple sclerosis patients responsive to interferon-beta therapy

2011 ◽  
Vol 18 (6) ◽  
pp. 788-798 ◽  
Author(s):  
M Chiarini ◽  
F Serana ◽  
C Zanotti ◽  
R Capra ◽  
S Rasia ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Interferon Beta ◽  
Central Memory ◽  
T Cell Subsets ◽  
Individual Treatment ◽  
Cell Phenotype ◽  
Multiple Sclerosis Patients

Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy. Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population. Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the ‘central memory-like’ Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy. Conclusions: The selective increase of ‘central memory-like’ subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.

Reduction of SSI by Hydrogen and its Microscopic Morphology

2012 ◽  
Vol 487 ◽  
pp. 672-676
Author(s):  
Jun Guo Li ◽  
Wei Tian ◽  
Shou Zhang Li
Keyword(s):  
Particle Size ◽  
Compressive Strength ◽  
Wastewater Treatment ◽  
High Activity ◽  
Iron Content ◽  
Sponge Iron ◽  
Reduction Temperature ◽  
Microscopic Morphology ◽  
Uniform Particle Size

Spherical sponge iron (SSI) with high activity and intension possesses potential characteristics to be utilized as wastewater treatment material, such as higher iron content, uniform particle size, higher compressive strength, etc. Observation on apparent morphology of exterior and microscopic morphology of SSI reduced by hydrogen under different temperature was carried on with SEM. When the reductive temperature was relatively lower than T4, the quantities of iron grain in exterior and interior of SSI increased with the increasing of temperature. When the temperature was elevated to T5, the particle size of iron grain was increased, and lots of macro-holes formed, especially in the interior section of SSI. When the temperature was T4, the SSI possesses more favorable ability to remove pollutant from wastewater. Moreover, the iron content in SSI was mostly reach to the summit under this temperature. In summarization, the reduction temperature should be controlled under T4 temperature if the sponge iron was utilized in wastewater treatment.

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