scholarly journals New Protein Vector ApE1 for Targeted Delivery of Anticancer Drugs

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
N. V. Pozdniakova ◽  
N. V. Gorokhovets ◽  
N. V. Gukasova ◽  
A. V. Bereznikova ◽  
E. S. Severin
Keyword(s):  
Targeted Delivery ◽  
Tumor Targeting ◽  
Drug Loading ◽  
Bacterial Biomass ◽  
Receptor Binding Domain ◽  
Producer Strain ◽  
E Coli ◽  
Cytotoxic Compound ◽  
Soluble State ◽  
New Protein

A new chimeric geneApE1encoding the receptor-binding domain of the humanalpha-fetoprotein fused to a sequence of 22 glutamic acid residues was constructed. A new bacterial producer strainE. coliSHExT7 ApE1 was selected for ApE1 production in a soluble state. A simplified method was developed to purify ApE1 from bacterial biomass. It was shown that the new vector protein selectively interacts with AFP receptors on the tumor cell surface and can be efficiently accumulated in tumor cells. In addition, ApE1 was shown to be stable in storage and during its chemical modification. An increased number of carboxyl groups in the molecule allows the production of cytotoxic compound conjugates with higher drug-loading capacity and enhanced tumor targeting potential.

scholarly journals Development of the Method to Produce Functionally Active Recombinant Streptavidin in Escherichia coli Cells

2020 ◽  
pp. 218-229
Author(s):  
Eugenia E. Bashmakova ◽  
Alexander N. Kudryavtsev ◽  
Ludmila A. Frank
Keyword(s):  
Escherichia Coli ◽  
Targeted Delivery ◽  
Solid Phase ◽  
Affinity Purification ◽  
Host Cells ◽  
Stable Complex ◽  
Active Protein ◽  
E Coli ◽  
Fundamental Medicine ◽  
Soluble State

Streptavidin is a homotetrameric protein produced by Streptomyces avidinii, each subunit of which binds biotin (vitamin H), forming a stable complex (Kd = 10-15 М). Streptavidin-biotin coreaction is widely used in analytical systems, for targeted delivery of compounds, for affinity purification, etc. The aim of this study was to develop a rational technique to produce functionally active recombinant streptavidin. Recombinant Escherichia coli strains producing minimal core and full-sized streptavidin variants were obtained. The E. coli BL21 Codon Plus (DE3) RIPL, as host cells, and the pET19b plasmid carrying gene of minimally-sized core (miniSAV) or full-sized (SAV) streptavidin were used. Synthesis of miniSAV results in its localization as insoluble inclusion bodies. Denatured miniSAV yield was 130 mg per liter of E. coli c ulture. T he r enaturation g ives o nly 10- 15 % of the functionally active protein. Full-sized streptavidin localizes in the cytoplasm in a soluble state, but its toxicity causes low yield of the protein (10-13 mg per liter of the culture). The induction of SAV synthesis at the end of the logarithmic stage of cell growth was found to increase the yield of SAV approximately 2-fold. The yield of functionally active protein was 30 mg per liter culture. SAV was produced practically in individual state after affine chromatography on 2-iminobiotin agarose. One molecule of full-sized streptavidin bound 3.9 biotin molecules as was shown by colorimetric analysis using HABA (4-hydroxyazobenzene-2-carboxylic acid). Both streptavidins form sandwichtype complexes with biotinylated molecules in solid-phase microassay conditions. E. coli BL21 Codon Plus (DE3) RIPL/pET19bSAV strain was stable during storage with 20 % glycerol at -70 °С, which was shown by repeated two-year reseeding. The streptavidin producing strain (E. coli BL21 Codon Plus (DE3) RIPL/pET19bSAV) is deposited in the Collection for extremophile microorganisms and type cultures (Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk), No. 3505. The method for producing functionally active recombinant streptavidin developed in this study ensures its availability for biotechnological research

Development and Evaluation of Particulate Microcarriers of Adapalene as a Topical Delivery System

2019 ◽  
Vol 9 (3) ◽  
pp. 222-233
Author(s):  
Divya D. Jain ◽  
Namita D. Desai
Keyword(s):  
Patient Compliance ◽  
Targeted Delivery ◽  
Ex Vivo ◽  
Acne Vulgaris ◽  
Drug Loading ◽  
Topical Therapy ◽  
Skin Irritation ◽  
Topical Delivery ◽  
Diffusion Method ◽  
Topical Gel

Background: Adapalene is a promising third generation retinoid used in the topical treatment of acne vulgaris. However, the major drawback associated with conventional topical therapy of Adapalene is the ‘retinoid reaction’ which is dose-dependent and characterized by erythema, scaling and burning sensation at the application sites. Microparticulate drug delivery can play a major role in reducing side effects and providing better patient compliance due to targeted delivery. Methods: Adapalene microparticles were prepared using quasi emulsion solvent diffusion method. The effects of formulation variables including polymer ratios, amounts of emulsifier, drug loading and process variables such as stirring time and speed on the physical characteristics of microparticles were investigated. The developed microparticles were characterized by DSC and SEM. Adapalene microparticles were incorporated into Carbopol 971 NF gel for ease of topical delivery. Results: Adapalene microparticulate topical gel showed sustained drug release over 8 hours in in vitro studies. The amount of drug retained in the rat skin during ex vivo studies was higher in the microparticulate topical gel (227.43 ± 0.83 µg/cm2) as compared to the marketed formulation (81.4 ± 1.11 µg/cm2) after 8 hours indicating localized and sustained drug action that can be useful in treating acne vulgaris. The safety of optimized Adapalene gel determined by skin irritation studies performed on Sprague Dawley rats showed no irritation potential. Conclusion: Microparticles can provide promising carrier systems to deliver Adapalene, improving patient compliance due to enhanced skin deposition, localized and sustained action with reduced associated irritant effects.

Fluorescence turn-off magnetic COF composite as a novel nanocarrier for drug loading and targeted delivery

2021 ◽  
Vol 311 ◽  
pp. 110713 ◽  
Author(s):  
Kai Zhao ◽  
Peiwei Gong ◽  
Jie Huang ◽  
Yan Huang ◽  
Dandan Wang ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Drug Loading

scholarly journals Tumor-Targeting Peptides Search Strategy for the Delivery of Therapeutic and Diagnostic Molecules to Tumor Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 314
Author(s):  
Maria D. Dmitrieva ◽  
Anna A. Voitova ◽  
Maya A. Dymova ◽  
Vladimir A. Richter ◽  
Elena V. Kuligina
Keyword(s):  
Phage Display ◽  
Cell Sorting ◽  
Targeted Delivery ◽  
Tumor Targeting ◽  
Search Strategy ◽  
Tumor Therapy ◽  
Therapeutic Agents ◽  
Phage Libraries

Background: The combination of the unique properties of cancer cells makes it possible to find specific ligands that interact directly with the tumor, and to conduct targeted tumor therapy. Phage display is one of the most common methods for searching for specific ligands. Bacteriophages display peptides, and the peptides themselves can be used as targeting molecules for the delivery of diagnostic and therapeutic agents. Phage display can be performed both in vitro and in vivo. Moreover, it is possible to carry out the phage display on cells pre-enriched for a certain tumor marker, for example, CD44 and CD133. Methods: For this work we used several methods, such as phage display, sequencing, cell sorting, immunocytochemistry, phage titration. Results: We performed phage display using different screening systems (in vitro and in vivo), different phage libraries (Ph.D-7, Ph.D-12, Ph.D-C7C) on CD44+/CD133+ and without enrichment U-87 MG cells. The binding efficiency of bacteriophages displayed tumor-targeting peptides on U-87 MG cells was compared in vitro. We also conducted a comparative analysis in vivo of the specificity of the accumulation of selected bacteriophages in the tumor and in the control organs (liver, brain, kidney and lungs). Conclusions: The screening in vivo of linear phage peptide libraries for glioblastoma was the most effective strategy for obtaining tumor-targeting peptides providing targeted delivery of diagnostic and therapeutic agents to glioblastoma.

Multivesicular liposome: A lipid-based drug delivery system for efficient drug delivery

2021 ◽  
Vol 27 ◽  
Author(s):  
Bapi Gorain ◽  
Bandar E. Al-Dhubiab ◽  
Anroop Nair ◽  
Prashant Kesharwani ◽  
Manisha Pandey ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Sustained Release ◽  
Delivery System ◽  
Targeted Delivery ◽  
Drug Loading ◽  
Therapeutic Agents ◽  
Laboratory Research ◽  
Efficacy And Safety ◽  
Liposomal Delivery ◽  
Proteins And Peptides

: The advancement of delivery tools for therapeutic agents has brought several novel formulations with increased drug loading, sustained release, targeted delivery, and prolonged efficacy. Amongst the several novel delivery approaches, multivesicular liposome has gained potential interest because this delivery system possesses the above advantages. In addition, this multivesicular liposomal delivery prevents degradation of the entrapped drug within the physiological environment while administered. The special structure of the vesicles allowed successful entrapment of hydrophobic and hydrophilic therapeutic agents, including proteins and peptides. Furthermore, this novel formulation could maintain the desired drug concentration in the plasma for a prolonged period, which helps to reduce the dosing frequencies, improve bioavailability, and safety. This tool could also provide stability of the formulation, and finally gaining patient compliance. Several multivesicular liposomes received approval for clinical research, while others are at different stages of laboratory research. In this review, we have focused on the preparation of multivesicular liposomes along with their application in different ailments for the improvement of the performance of the entrapped drug. Moreover, the challenges of delivering multivesicular vesicles have also been emphasized. Overall, it could be inferred that multivesicular liposomal delivery is a novel platform of advanced drug delivery with improved efficacy and safety.

Redox-Sensitive Ultrashort Peptide Hydrogel with Tunable Mechanical Properties for Anti-Tumor Drug Delivery

2020 ◽  
Vol 16 (11) ◽  
pp. 1588-1599
Author(s):  
Yiping Li ◽  
Ying Zhu ◽  
Shiyao Luo ◽  
Yue He ◽  
Zhewei Huang ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Targeted Delivery ◽  
Subcutaneous Tissue ◽  
Drug Loading ◽  
Gelation Time ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
The Cross ◽  
Hydrogel System

In this study, we report a new ultrashort peptide (LOC), which forms a redox-sensitive hydrogel after cross-linking with the mild oxidant H2 O2 and used it for tumor-targeted delivery of doxorubicin hydrochloride (DOX). LOC gelled within a few minutes in low-concentration H2 O2 solution. The concentration of H2 O2 significantly altered the gelation time and mechanical properties of the hydrogel. The in vitro micromorphology, secondary structure and rheology characterization of cross-linked hydrogels confirmed the sensitivity and injectability to reducing agent. The cross-linked hydrogel had a strong drug loading capacity, and the drug was released in a GSH concentration-dependent manner, following the Fick diffusion model. In addition, the cross-linked hydrogel showed no cytotoxicity to normal fibroblasts, and no damage to the subcutaneous tissue of mice was observed. In vitro cytotoxicity experiments showed that the DOX-hydrogel system exhibited good anti-cancer efficacy. In vivo studies using 4T1 tumor-bearing mice showed that the DOX-hydrogel system had a significant inhibitory effect on tumors. Therefore, the newly designed redox-sensitive hydrogel can effectively enhance the therapeutic efficacy of DOX and reduce toxicity, making it an attractive biological material.

A Low Dose of Hydrous Icaritin Nano-Formulation with Remarkable Efficacy and Tumor Targeting in Cancer Therapy

2021 ◽  
Vol 17 (10) ◽  
pp. 2003-2013
Author(s):  
Jingxin Fu ◽  
Yian Wang ◽  
Haowen Li ◽  
Likang Lu ◽  
Hui Ao ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Tumor Targeting ◽  
Low Dose ◽  
Drug Loading ◽  
Tumor Therapy ◽  
High Dose ◽  
Inhibition Rate ◽  
Tumor Inhibition ◽  
Nano Formulation ◽  
Tumor Inhibition Rate

Background: The use of chemotherapeutic drugs is restricted in the tumor-therapy because of the severely toxic and side effects among most important factors. The active herbal extracts are always used as a high dose while in the tumortherapy to achieve good anti-tumor effects. Hydrous icaritin has a high activity while there are few existing dosage forms as a result of low solubility in water and poor bioavailability. Results: The prepared hydrous icaritin nanorods (DP-HICT NRs) using mPEG2000-DSPE as a stabilizer, presented a narrow distribution of particle size with of 217 nm and a properly high drug-loading content of approximately 65.3±1.5%. A low dose of hydrous icaritin nano-formulation shows remarkable efficacy in cancer therapy (tumor inhibition rate: 61.36±10.80%) compared with the same dose of Paclitaxel injection (tumor inhibition rate: 66.80±4.43%), which approved as medicaments. Not only that, DP-HICT NRs can escape the clearance of the immune system and enhance targeting ability to the tumor site with only one excipient and such a low dose. Conclusions: This kind of nanoparticles contain a low dose of HICT used mPEG2000-DSPE as a stabilizer, while can achieve good tumor targeting as some active targeting agents and an anti-tumor effect as the PTX injection. There are broad prospects in drug safety, anti-tumor efficacy and even prognosis.

Therapeutic Properties of PDMS Nanoparticles: A Promising New Drug Delivery Vehicle Against Inflammatory Conditions

2021 ◽  
Vol 24 ◽  
Author(s):  
Aiswarya Anilkumar Ajitha ◽  
Sri SivaKumar ◽  
Gayathri Viswanathan ◽  
Sabulal Baby ◽  
Prabath Gopalakrishnan Biju
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Release Kinetics ◽  
Drug Loading ◽  
Systemic Circulation ◽  
Biological Evaluation ◽  
Raw 264.7 Cells ◽  
Morphological Examination ◽  
Inflammatory Conditions ◽  
Anti Inflammatory

Background: Over the last few decades, there has been a stupendous change in the area of drug delivery using particulate delivery systems, with increasing focus on nanoparticles in recent times. Nanoparticles helps to improve and alter the pharmacodynamic properties and pharmacokinetics of various types of drug molecules. These features help to protect the drug entity in the systemic circulation, access of the drug to the chosen sites, and to deliver the drug in a controlled and sustained rate at the site of action. Objective: Nanoparticle based targeted delivery of anti-inflammatory drugs/signal modulatory agents to the cytoplasm or nuclei of the targeted cell can significantly enhance the precision and efficacy of intended therapeutic activity. To this end, we report ligand free, enhanced intra-nuclear delivery model of anti-inflammatory therapeutics via PDMS nanoparticles. Method: PDMS nanoparticles were prepared by sacrificial silica template-based approach and details of their characterization for suitability as a nanoparticle-based delivery material is detailed herein. Results: Biological evaluation for compatibility was carried out and the results showed that the PDMS nanoparticle has no toxicity on RAW 264.7 cells in the concentration range of 10, 20, 40, 60, 80, 100 and 120 μg/mL in culture. Biocompatibility and absence of toxicity was determined by morphological examination and cell viability assays. Drug loading and release kinetics were carried out with the anti-inflammatory drug Diclofenac. Conclusion: In this paper we clearly demonstrate the various aspects of nanoparticle articulation, characterization, effect of their characteristics and their applications as a non-toxic drug delivery molecule for its potential applications in therapeutic delivery of drugs for sustained release.

scholarly journals Advances in Polyhydroxyalkanoate Nanocarriers for Effective Drug Delivery: An Overview and Challenges

Nanomaterials ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 175
Author(s):  
Priyanka Prakash ◽  
Wing-Hin Lee ◽  
Ching-Yee Loo ◽  
Hau Seung Jeremy Wong ◽  
Thaigarajan Parumasivam
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
In Situ Polymerization ◽  
Drug Loading ◽  
Controlled Drug Release ◽  
Production Costs ◽  
Natural Polymers ◽  
High Production ◽  
The Many

Polyhydroxyalkanoates (PHAs) are natural polymers produced under specific conditions by certain organisms, primarily bacteria, as a source of energy. These up-and-coming bioplastics are an undeniable asset in enhancing the effectiveness of drug delivery systems, which demand characteristics like non-immunogenicity, a sustained and controlled drug release, targeted delivery, as well as a high drug loading capacity. Given their biocompatibility, biodegradability, modifiability, and compatibility with hydrophobic drugs, PHAs often provide a superior alternative to free drug therapy or treatments using other polymeric nanocarriers. The many formulation methods of existing PHA nanocarriers, such as emulsion solvent evaporation, nanoprecipitation, dialysis, and in situ polymerization, are explained in this review. Due to their flexibility that allows for a vessel tailormade to its intended application, PHA nanocarriers have found their place in diverse therapy options like anticancer and anti-infective treatments, which are among the applications of PHA nanocarriers discussed in this article. Despite their many positive attributes, the advancement of PHA nanocarriers to clinical trials of drug delivery applications has been stunted due to the polymers’ natural hydrophobicity, controversial production materials, and high production costs, among others. These challenges are explored in this review, alongside their existing solutions and alternatives.

Removal of reactive dyes from aqueous solution by different bacterial genera

1996 ◽  
Vol 34 (10) ◽  
pp. 89-95 ◽  
Author(s):  
Hu Tai-Lee
Keyword(s):  
Aqueous Solution ◽  
Reactive Dyes ◽  
Bacterial Biomass ◽  
Gram Negative Bacteria ◽  
Adsorption Parameters ◽  
Gram Negative ◽  
E Coli ◽  
Gram Positive Bacteria ◽  
Mixed Biomass ◽  
Decreasing Ph

The use of biomass for the removal of reactive dyes from an aqueous solution with different bacterial genera has been investigated. Three Gram-negative bacteria: Aeromonas sp., P. luteola and E. coli, and two Gram-positive bacteria: B. subtilis and S. aureus and a mixed biomass of activated sludge are the tested biosorbents. Dead cells of Gram-negative bacteria have a higher specific adsorption capacity than the living cells. The dye removal is in the order of Aeromonoas sp. > P. luteola > E. coli. The adsorption equilibrium can be reached within one hour. Due to the positively charged cells at acidic pH, the removal of reactive dyes increases with decreasing pH. Evaluating the adsorption parameters, bacterial biomass exhibits stable adsorption characteristics, which makes it a suitable adsorbent for different dye compounds.

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