Drug Carrier Systems Research Articles

Lysozyme and Human Serum Albumin Proteins as Potential Nitric Oxide Cardiovascular Drug Carriers: Theoretical and Experimental Investigation.

Nitric oxide-containing drugs present a critical remedy for cardiovascular diseases. Nitroglycerin (NG, O-NO) and S-nitrosoglutathione (SNG, S-NO) are the most common nitric oxide drugs for cardiovascular diseases. Insights regarding the binding affinity of NO drugs with lysozyme and human serum albumin (HSA) proteins and their dissociation mechanism will provide inquisitive information regarding the potential of the proteins as drug carriers. For the first time, the binding interactions and affinities are investigated using molecular docking, conventional molecular dynamics, steered molecular dynamics, and umbrella sampling to explore the ability of both proteins to act as nitric oxide drug carriers. The molecular dynamics simulation results showed higher stability of lysozyme-drug complexes compared to HSA. For lysozyme, cardiovascular drugs were bound in the protein cavity mainly by the electrostatic and hydrogen bond interactions with residues ASP53, GLN58, ILE59, ARG62, TRP64, ASP102, and TRP109. For HSA, key binding residues were ARG410, TYR411, LYS414, ARG485, GLU450, ARG486, and SER489. The free energy profiles produced from umbrella sampling also suggest that lysozyme-drug complexes had better binding affinity than HSA-drug. Binding characteristics of nitric oxide-containing drugs NG and SNG to lysozyme and HSA proteins were studied using fluorescence and UV-vis absorption spectroscopy. The relative change in the fluorescence intensity as a function of drug concentrations was analyzed using Stern-Volmer calculations. This was also confirmed by the change in the UV-vis spectra. Fluorescence quenching results of both proteins with the drugs, based on the binding constant values, demonstrated significantly weak binding affinity to NG and strong binding affinity to SNG. Both computational and experimental studies provided important data for understanding protein-drug interactions and will aid in developing potential drug carrier systems in cardiovascular diseases.

The Importance of Highly Connected Building Units in Reticular Chemistry: Thoughtful Design of Metal-Organic Frameworks.

The prediction of crystal structures assembled in three dimensions has been considered for a long time, simultaneously as a chemical wasteland and a certain growth point of the chemistry of the future. Less than 30 years after Roald Hoffmann's statement, we can categorically affirm that the elevation of reticular chemistry and the introduction of metal-organic frameworks (MOFs) significantly tackled this tridimensional assembly issue. MOFs result from the assembly of organic polytopic organic ligands bridging metal nodes, clusters, chains, or layers together into mostly three-periodic open frameworks. They can exhibit extremely high porosity and offer great potential as revolutionary catalysts, drug carrier systems, sensors, smart materials, and, of course, separation agents. Overall, the progressive development of reticular chemistry has been a game changer in materials chemistry during the last 25 years.Such diverse properties often result not only from the selected organic and inorganic molecular building blocks (MBBs) but also from their distribution within the framework. Indeed, the size and shape of the porous system, as well as the location of active sites influence the overall properties. Therefore, in the continuity of achieving the crystallization of three-periodic structures, chemists and crystal engineers faced the next challenge, as summarized by John Maddox: "it remains in general impossible to predict the structure of even the simplest crystallographic solids from knowledge of their chemical composition". This is where rational design takes place.In this Account, we detail three specific approaches developed by our group to facilitate the design and assembly of finely tuned MOFs. All are based on careful geometrical consideration and a deep study and understanding of the existing nets and topologies. We recognized that highly connected nets, if possible, edge-transitive, are ideal blueprints because their number is limited in contrast to nets with lower connectivity. Therefore, we embarked on taking advantage of existing highly connected MBBs, or, in parallel, promoting their formation to meet our requirements. This is achieved by utilizing externally decorated metal-organic polyhedra as supermolecular building blocks (SBBs), serving as a net-coding building unit, comprising the requisite connectivity and directional information coding for the chosen nets. The SBB approach allowed the synthesis of several families of SBB-based MOFs, including fcu, rht, and gea-MOFs, that are detailed here.The second strategy is directly inherited from the success of the SBB approach. In seeking highly connected building units, our group naturally expanded its research focus to nets that can be deconstructed into layers, pillared in various ways. In the supermolecular building layer (SBL) approach, the layers have an almost infinite connectivity, and the framework backbone is fixed in two dimensions while the third is free for pillar expansion and functionalization. The cases of trigonal pillaring leading to rtl, eea, and apo MOFs as well as the quadrangular pillaring leading to a family of tbo-MOFs are discussed here, along with recent cases of highly connected pillars in pek and aea-MOFs.Finally, our experience with highly coordinated MBBs led us to develop a novel way to use them as secondary building units of lower connectivity and unlock the possibility of assembling a novel class of zeolite-like MOFs (ZMOFs). The case of the Zr-sod-ZMOFs designed through a cantellation strategy is described as a future leading direction of MOF design.

Study of Uptake Mechanisms of Halloysite Nanotubes in Different Cell Lines.

PurposeHalloysite nanotubes (HNTs) are a natural aluminosilicate clay with a chemical formula of Al2Si2O5(OH)4×nH2O and a hollow tubular structure. Due to their peculiar structure, HNTs can play an important role as a drug carrier system. Currently, the mechanism by which HNTs are internalized into living cells, and what is the transport pathway, is still unclear. Therefore, this study aimed at establishing the in vitro mechanism by which halloysite nanotubes could be internalized, using phagocytic and non-phagocytic cell lines as models.MethodsThe HNT/CURBO hybrid system, where a fluorescent probe (CURBO) is confined in the HNT lumen, has been used as a model to study the transport pathway mechanisms of HNTs. The cytocompatibility of HNT/CURBO on cell lines model was investigated by MTS assay. In order to identify the internalization pathway involved in the cellular uptake, we performed various endocytosis-inhibiting studies, and we used fluorescence microscopy to verify the nanomaterial internalization by cells. We evaluated the haemolytic effect of HNT/CURBO placed in contact with human red blood cells (HRBCs), by reading the absorbance value of the supernatant at 570 nm.ResultsThe HNT/CURBO is highly biocompatible and does not have an appreciable haemolytic effect. The results of the inhibition tests have shown that the internalization process of nanotubes occurs in an energy-dependent manner in both the investigated cell lines, although they have different characteristics. In particular, in non-phagocytic cells, clathrin-dependent and independent endocytosis are involved. In phagocytic cells, in addition to phagocytosis and clathrin-dependent endocytosis, microtubules also participate in the halloysite cellular trafficking. Upon internalization by cells, HNT/CURBO is localized in the cytoplasmic area, particularly in the perinuclear region.ConclusionUnderstanding the cellular transport pathways of HNTs can help in the rational design of novel drug delivery systems and can be of great value for their applications in biotechnology.

Cation Lipid-Assisted PEG6-PLGA Polymer Nanoparticles Encapsulated Knocking Down Long ncRNAs Reverse Non-Coding RNA of Xist Through the Support Vector Machine Model to Regulate the Molecular Mechanisms of Gastric Cancer Cell Apoptosis.

Gastric adenocarcinoma (GAC) is one kind of gastric cancer with a high incidence rate and mortality. It is essential to study the etiology of GAC and provide theoretical guidance for the prevention and treatment of GAC. Bioinformatics was used via differential expression analysis, weighted gene co-expression network analysis, gene set enrichment analysis, and a training support vector machine (SVM) model to construct a TSIX/mir-320a/Rad51 network as the research index of GAC disease. On the basis of CRISPR/Cas9 gene editing technology, the present study utilizes the Cation lipid-assisted PEG-6-PLGA polymer nanoparticle (CLAN) drug carrier system to prepare the target knock-out TSIX drug with CRISPR/CaS9 nucleic acid. Knocking down lncRNA TSIX restored the suppression role of miR-320a on Rad51 and inhibited the Rad51 expression. Simultaneously, this ceRNA network activated the ATF6 signaling pathway after endoplasmic reticulum stress to promote GAC cells' apoptosis and inhibit the disease. TSIX/miR-320a/Rad51 network may be a potential biological target of GAC disease and provides a new strategy for treating GAC disease.

Phyto-Phospholipid Complexation as a Novel Drug Delivery System for Management of Cancer with Better Bioavailability: Current Perspectives and Future Prospects.

Cancer is the foremost cause of death, and it supports the need for the identification of novel anticancer drugs to improve the efficacy of current-therapy. While the synthetic anticancer drug is associated with numerous side effects. Hence the plant active or phytoconstituents are in high demand for the treatment of cancer due to minimum side effects. But the polar nature of phytoconstituents hindered the absorption of the drug and lowered the therapeutic efficacy. The plant activity incorporated into Phyto-phospholipid Complexation can enhance bioavailability and improved therapeutic efficacy. In this review article, advantages, limitation and application of Phyto-phospholipid complexes have been illustrated. The article highlights the application of Phyto-phospholipid complexes as a promising drug carrier system to treat cancer.

Screening of Electrolyte Complexes Formed Between Dextran Sulfate and Amine Structures of Small-Molecule Drugs.

Formation of an electrolyte complex using the electrostatic interactions between a polyanionic polymer and a cationic drug is a simple and efficient method of preparing a colloidal drug carrier system. Dextran sulfate, with a negatively charged sulfate group, was reacted in an acetate buffer solution of pH 3 with positively charged 1° amine, 2° amine, 3° amine, piperazine, and piperidine structures from 24 small-molecule drugs. The electrolyte complex was formed from 15 drugs, 63% of those tested. The tendency to form the electrolyte complex was in the order of piperazine and piperidine >3° amine >>2° amine. The drugs with the 1° amine structure failed to form an electrolyte complex. The mean particle sizes were in the range of 50-740 nm, and most of them showed a submicron colloidal dispersion of <400 nm. Regarding drug encapsulation efficiency (%), 11 drugs with piperazine, piperidine, and 3° amine structures showed 60-98% efficiency, which was fairly high. The results suggest that directly forming the electrolyte complex with dextran sulfate yields promising structural attributes as a submicron colloidal drug carrier system.

Analyzing release kinetics modelling, cytotoxicity and stability testing of gabapentin linked thiol and cysteine functionalized monodispersed gold nanoparticles

Nanomedicine has emerged as an area of research that has earned a lot of attention in the past decade along with frequent and sustained advancements leading to its extensive plethora of biomedical applications. Following the same, the drug carrier systems like gold nanoparticles (AuNPs) have become the success stories with many marketed formulations now and has proved to be a most suitable answer to the drug delivery concers due to their exclusive electrical and optical properties. They serve as one of the best surfaces to either adsorb, attach, or conjugate and exhibit remarkable optoelectronic, physicochemical, morphological and functional properties. In this study, Gabapentin (GBP) a known FDA approved anti-epileptic drug is selected for improving its pharmaceutical limitations and we have synthesized monodispersed AuNPs for GBP conjugation using citrate reduction method. Here the research group has modified AuNP surfaces with three different thiol moieties namely, Mercaptopropionic acid (3-MPA), 11-Mercaptoundecanoic acid (11-MUA) and the amino acid L-Cysteine (L-Cys) and then attached the GBP with these linkers. The synthesized GBP–AuNP nano-conjugate moieties were further characterized and tested for their in-vitro cytotoxicity, release kinetics and stability properties. The in-vitro release kinetics and cytotoxicity (MTT-Assay) analysis of the formulated GBP–AuNP nano-conjugates along with all the 3 types of linkers was carried out and after the data analysis for the same, it was observed that the GBP–AuNP nano-conjugate with L-Cys linker exhibited the sustained release pattern and non- significant cytotoxicity followed by MUA and MPA, respectively. Moreover, the assessment of GBP-AuNPs evaluated through the comprehensive release kinetics analysis, reinforced the GBP-thiol linkers as potentially more effective and competent than GBP alone. Furthermore, all the experimental data was validated by statistical method, and it can be concluded from the present study that the symmetrical monodispersed AuNPs formulation coated with stable functionalized thiol layer were synthesized with minimal cytotoxicity and can be further explored as an efficient drug delivery system for therapeutic application.

Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

BackgroundMelittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done.ResultsThis study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups.ConclusionsOur study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

Temperature-Dependent Dynamical Evolution in Coum/SBE-β-CD Inclusion Complexes Revealed by Two-Dimensional FTIR Correlation Spectroscopy (2D-COS).

A combination of Fourier transform infrared spectroscopy in attenuated total reflectance geometry (FTIR-ATR) and 2D correlation analysis (2D-COS) was applied here for the first time in order to investigate the temperature-dependent dynamical evolution occurring in a particular type of inclusion complex, based on sulfobutylether-β-cyclodextrin (SBE-β-CD) as hosting agent and Coumestrol (7,12-dihydorxcoumestane, Coum), a poorly-soluble active compound known for its anti-viral and anti-oxidant activity. For this purpose, synchronous and asynchronous 2D spectra were calculated in three different wavenumber regions (960–1320 cm−1, 1580–1760 cm−1 and 2780–3750 cm−1) and over a temperature range between 250 K and 340 K. The resolution enhancement provided by the 2D-COS offers the possibility to extract the sequential order of events tracked by specific functional groups of the system, and allows, at the same time, the overcoming of some of the limits associated with conventional 1D FTIR-ATR analysis. Acquired information could be used, in principle, for the definition of an optimized procedure capable to provide high-performance T-sensitive drug carrier systems for different applications.

Influence of process and formulation parameters on the preparation of solid lipid nanoparticles by dual centrifugation

A promising strategy to formulate poorly water-soluble active pharmaceutical ingredients (APIs) is the application of these substances in solid lipid nanoparticles. These drug carrier systems are commonly prepared by high-pressure homogenization above the melting temperature of the utilized lipid. While being very useful for large-scale production this method is quite resource-consuming and does not allow simultaneous processing of multiple samples, e.g. for screening purposes. For this reason, an alternative manufacturing process, dual centrifugation, is introduced to prepare solid lipid nanoparticles. The ingredients of the dispersions were directly weighed into 2 mL vessels at room temperature without the need to prepare a pre-mix emulsion. Due to an additional rotation of the samples in the heated centrifuge as well as the addition of grinding media an intensive stressing of the samples was achieved. The emulsification process was finished within 10 min with sample temperatures of up to 90 °C being obtained. Dependent on the process set-up like grinding media size, filling ratio or process temperature and the composition of the lipid formulation, the achieved particles sizes were below 200 nm and had a narrow, monomodal size distribution.

The Use of Heptamethine Cyanine Dyes as Drug-Conjugate Systems in the Treatment of Primary and Metastatic Brain Tumors.

Effective cancer therapeutics for brain tumors must be able to cross the blood-brain barrier (BBB) to reach the tumor in adequate quantities and overcome the resistance conferred by the local tumor microenvironment. Clinically approved chemotherapeutic agents have been investigated for brain neoplasms, but despite their effectiveness in peripheral cancers, failed to show therapeutic success in brain tumors. This is largely due to their poor bioavailability and specificity towards brain tumors. A targeted delivery system might improve the efficacy of the candidate compounds by increasing the retention time in the tumor tissue, and minimizing the numerous side effects associated with the non-specific distribution of the chemotherapy agent. Heptamethine cyanine dyes (HMCDs) are a class of near-infrared fluorescence (NIRF) compounds that have recently emerged as promising agents for drug delivery. Initially explored for their use in imaging and monitoring neoplasms, their tumor-targeting properties have recently been investigated for their use as drug carrier systems. This review will explore the recent developments in the tumour-targeting properties of a specific group of NIRF cyanine dyes and the preclinical evidence for their potential as drug-delivery systems in the treatment of primary and metastatic brain tumors.

Zolmitriptan Intranasal Spanlastics for Enhanced Migraine Treatment; Formulation Parameters Optimized via Quality by Design Approach

Zolmitriptan is a potent second-generation triptan prescribed for migraine attacks. It suffers low bioavailability (40%) after oral administration due to the hepatic first-pass metabolism. Spanlastics are surfactant-based elastic vesicular drug carrier systems. This study aimed to design and optimize intranasal spanlastic formulations as an alternative approach that directly targets brain delivery, enhancing its bioavailability and avoiding the first-pass effect. The quality by design approach was applied to correlate the formulation parameters (Span 60 and Tween 80 concentrations) and critical quality attributes (entrapment efficiency (EE%) and particle size). Spanlastic formulations were designed based on response surface central composite design and prepared via an ethanol injection method. Designed formulations were characterized by EE% and particle size measurements to select the optimized formula (with a combination of small particle size and high EE%). The optimized formula was further subjected to transmission electron microscopy, zeta potential measurement and ex vivo permeation study. The optimized formulation showed a particle size of 117.5 nm and EE% of 45.65%, with a low percentage of error between the observed and predicted values. Seventy percent of zolmitriptan was permeated through the nasal membrane within 30 min, and it completely permeated within 2 h with a significantly higher steady-state flux compared to plain gel. This study introduced a successful and promising intranasal formulation suitable for further brain delivery analysis.

Development of Mupirocin- Tinidazole solid- Lipid Nanoparticles Loaded Topical gel for the Management of Bacterial Wound Infections

Solid lipid nanoparticles (SLNs) are novel drug carrier system which consists of a solid matrix composed of a lipid being solid at both room and body temperatures with a mean Particle Size (PS) between 50 and 1000 nm Mupirocin -Tinidazole solid-lipid nanoparticles were prepared using hot homogenization technique using Glyceryl monosterate, Stearic acid, Tween 80 and Poloxamer 188 using hot homogenization technique. Size of the nanoparticles was in the range of 83 to 211 nm with the zeta potential values between -2.1 to -5.2. Atomic Force Microscopy (AFM) confirms the spherical shape of solid lipid nanoparticles. Entrapment efficiency was best in the F1 formulation. In vitro release of the pure drug was found to be 75% of mupirocin and 66.5% of tinidazole at the end of 1 hr. Drug release from SLNs dispersion followed Korsermeyrs peppas-model, indicating fickian diffusion drug release, while that from the gel followed non Fickian model drug release. Antibacterial activity of the SLNs was less but the SLNs based gel shows no significant difference in activity to that of standard drug gentamycin against aerobic bacteria. The SLNs dispersion exhibited physicochemical stability under refrigeration upto 45 days without significant difference in particle size. Best formulation was developed into a topical gel using sodium alginate and it was evaluated for pH, viscosity, spreadbility, extrudability, bloom strength, Minimum Inhibitory Concentration (MIC) and Methicillin resistant staphylococcus aureus (MRSA). Extrudability and spreadability parameters of the gel are similar to that of marketed Mupirocin 2% cream formulation

Application of iron/barium ferrite/carbon-coated iron nanocrystal composites in transcatheter arterial chemoembolization of hepatocellular carcinoma

Transcatheter arterial chemoembolization (TACE) has been widely used in clinical practice as a first-line treatment for unresectable hepatocellular carcinoma (HCC). However, the current therapeuticeffect of TACE is far from satisfactory and thus requires further improvement. TACE combined with multifunctional magnetic particles may be a promising approach for the treatment of HCC. In this study, we designed a new magnetic drug carrier system consisting of micron-sized iron powder, barium ferrite (BaFe12O19), and carbon-coated iron nanocrystals (CCINs). CCINs possess properties, such as high drug loading and sustained release. BaFe12O19 could attract both CCINs and iron powder to form larger clusters after magnetization. Altogether, the triple therapeutic effects of chemotherapeutic enhancement, embolization, and thermal ablation could be realized herein. Further experiments indicate that the system has a high drug-loading capacity, good controlled-release effect, and no significant cytotoxicity. Under the action of a medium-frequency magnetic induction device, the magnetic induction temperature could reach 43 °C in one min while the maximum temperature of 70.8 °C could be reached in 2.5 h. Overall, this new carrier system displayed excellent antitumor effects in a mouse model. Our findings demonstrate the great application prospects of this system in TACE for HCC.

Solid Dispersion: A Mechanistic and Realistic Approach on Antihypertensive Drug as a Drug Carrier System.

A major percentage of the new chemical entities are reported to have poor aqueous solubility. Several antihypertensive drugs used clinically have either low solubility or high hepatic metabolism, thereby presenting low bioavailability (BA) and high pharmacokinetic variability. Improving the aqueous solubility of drug molecules would assist in overcoming the variability, and several approaches for improving solubility have been reported. Solid dispersion (SD) is known as a potential technique to conquer the problem of poor aqueous solubility and low BA. Drug solubility is improved by increasing the wetting property of drugs. This review is focused on discussing various approaches to improve solubility, classification, and different approaches used for formulation of SDs, along with special emphasis on the application of the SD approach for improving solubility and eventually enhancing dissolution and increasing the BA of antihypertensive drugs. The review leads to the conclusion that the use of more than one polymeric carrier for formulating SDs might help in overcoming storage and stability issues and in increasing the commercial viability and success of SDs.

Formulation, Characterization and In vitro Drug Delivery of Vitexin Loaded Liposomes

Liposome is a spherical vesicle which contains atleast one lipid bilayer. Liposomes are used as a novel drug carriers because of its hydrophobic and hydrophilic nature, it has many advantages in the field of medical sciences. There are some other drug carriers like dendrimers, micelles, niosomes. Out of all, liposomes are considered to be the most promising agent for drug delivery. The uniqueness of liposome is when it is used as a pharmaceutical drug, it acts as a natural receptor. Thus it acts as an antigen and binds with the antibody (cancer cell) without causing any damage to the adjacent cells. For the synthesis of liposomes, a phospholipid is required. The liposomes can be synthesized using egg yolk and chloroform. So the basic phospholipid is obtained from egg yolk. For more stability, the liposomes are prepared using popc. The present work discuss about the effective preparation of drug loaded liposomes using popc (1- palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine). POPC is an important phospholipid for biophysical experiments. Additionally chloroform is used as the solvent for the liposome preparation. The drug chosen for liposome loading is vitexin (vxn), which is an effective therapeutic agent against inflammation and cancer. The vesicular size, shape, drug entrapment efficacy, stability, electrochemical property and drug releasing property of the formulated liposomes were characterized. The results showed that the formulated liposomes are considered as the better drug carrier system and good choice for biotransformation within the cell to reach the target site such as cancer cells. Even though available treatments like chemotherapy and radiation therapy, causes damage to the surrounding cells, the alternative drug transferring system such as liposomal mediated drug transfer within the cell is considered as good choice of treatment to avoid such complications. The aim of liposome mediated drug carrier system is to develop a method to reach the drug to the target site. After drug delivery at the target site, the liposomes are fused within the surface of the body. This is because of the pH of liposomes, which is at 7.4 and temperature is maintained at 37 oC. So, the vxn loaded liposomes are considered as the novel drug carriers for the successful targetted drug delivery.

Novel drug delivery strategies and gene therapy regimen as a promising perspective for management of psoriasis.

Psoriasis is an autoimmune disorder; however, an exact underlying mechanism responsible for psoriasis is yet not known. A hypothesis put forward is an abnormal proliferation of keratinocytes due to faulty signals brought about by T-cells. Due to the lack of evidence of the exact cause, a variety of treatments have been used of which topical therapy is usually the first option in most patients. Topical therapy has several shortcomings and barriers of drug delivary which may be effectively overcome using novel drug carrier systems which exhibit maximum penetration, controlled release, reduced irritancy and, overall, a better efficacy. Thus, novel treatment strategies based on gene therapy such as antisensing nucleotide, silencing RNA complex, stem cell therapy and antibody-based therapy are being envisaged. This review article discusses the concepts and background of current novel delivery systems and gene therapy tools for effective management of psoriasis.

Silver Nanoparticles as Carriers of Anticancer Drugs for Efficient Target Treatment of Cancer Cells.

Since the last decade, nanotechnology has evolved rapidly and has been applied in several areas, such as medicine, pharmaceutical, microelectronics, aerospace, food industries, among others. The use of nanoparticles as drug carriers has been explored and presents several advantages, such as controlled and targeted release of loaded or coupled drugs, and the improvement of the drug’s bioavailability, in addition to others. However, they also have some limitations, related to their in vivo toxicity, which affects all organs including the healthy ones, and overall improvement in the disease treatment, which can be unnoticeable or minimal. Silver nanoparticles have been increasingly investigated due to their peculiar physical, chemical, and optical properties, which allows them to cover several applications, namely in the transport of drugs to a specific target in the body. Given the limitations of conventional cancer chemotherapy, which include low bioavailability and the consequent use of high doses that cause adverse effects, strategies that overcome these difficulties are extremely important. This review embraces an overview and presentation about silver nanoparticles used as anticancer drug carrier systems and focuses a discussion on the state of the art of silver nanoparticles exploited for transport of anticancer drugs and their influence on antitumor effects.

Biocompatible valproic acid-coupled nanoparticles attenuate lipopolysaccharide-induced inflammation

Inflammatory diseases like sepsis are associated with dysregulated gene expression, often caused by an imbalance of epigenetic regulators, such as histone acetyltransferases (HATs) and histone deacetylases (HDACs), and consequently, altered epigenetic chromatin signatures or aberrant posttranslational modifications of signalling proteins and transcription factors. Thus, HDAC inhibitors (HDACi) are a promising class of anti-inflammatory drugs. Recently, an efficient drug delivery system carrying the class I/IIa selective HDACi valproic acid (VPA) was developed to circumvent common disadvantages of free drug administration, e.g. short half-life and side effects. The cellulose-based sulphated VPA-coupled (CV-S) nanoparticles (NPs) are rapidly taken up by cells, do not cause any toxic effects and are fully biocompatible. Importantly, VPA is intracellularly cleaved from the NPs and HDACi activity could be proven. Here, we demonstrate that CV-S NPs exhibit overall anti-inflammatory effects in primary human macrophages and are able to attenuate the lipopolysaccharide-induced inflammatory response. CV-S NPs show superior potential to free VPA to suppress the TLR-MyD88-NF-κB signalling axis, leading to decreased TNF-α expression and secretion.

Rationalizing Nanodeliverables for Effective L-Asparaginase Delivery in Chemotherapy: Update 2020

L-asparaginase is used as an effective line of treatment for acute lymphoblastic leukemia and lymphoma, however, the high cost for this treatment restricts the wide-scale clinical application. Genetic engineering technology is used to recombinantly express L-asparaginase, with high yield, which reduced the costs of production, and overall therapy. Despite the effectiveness of this therapy, intravenous injection of L-asparaginase has some side effects, such as allergic reactions, immunosuppression, pancreatitis, neurotoxicity, hepatitis, coagulopathy, and failure to produce antibodies. To overcome this limitation, Nano-delivery systems using nanoparticles as the carrier of L-asparaginase is used as a new type of drug carrier delivery system. It can increase the permeability of biofilms, enhance drug efficacy, reduce drug toxicity, change the distribution of drugs in the body, and improve bioavailability. In this review, we summarized the application of a variety of nano-lipid and polymers as protein recombinant drug carrier systems, and these nano-carrier systems facilitate to increase the blood circulation time, reduce side effects, and improve the biocompatibility of L-asparaginase medicine. The review specifically adds value as there is no article available that has attempted to elevate the emerging Nanodeliverables and their significance in delivering L- sparaginase safely by achieving maximum therapeutic efficacy.