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This review discusses lipid assemblies—from liposomes to solid lipid nanoparticles—as platforms for drug delivery. It covers design principles, targeting strategies, and manufacturing considerations.
Background: Skin is one the most important sites for administration of drugs to obtain desired pharmacological effects either locally or through systemic bioavailability; and this has placed the transdermal route of drug delivery as an attractive and as one of the most innovative areas for conducting drug delivery research. However the stratum corneum in skin creates hurdles and acts as significant barrier for the permeation of drugs through skin. Penetration enhancers play a pivotal role to overcome such barriers and help enhance the permeation of drug through skin. However, penetration enhancement technology is challenging development and needs to be properly and skillfully addressed. Objective: The present investigation aimed to study the penetration enhancing effect of a newly synthesized alcohol derivative of an acyclic monoterpene (Tetrahydrogeraniol-THG). Methodology: The new derivative, 5,9-Dimethyl-1-Decanol (DIMDOL), has been synthesized by a chemical reaction of the THG with Grignard reagent and ethylene oxide. Permeation enhancing effect of the synthesized derivative was explored for better transdermal penetration of the two model drugs viz. tramadol hydrochloride and 5-fluorouracil (5-FU) through the excised rat skin by conducting in-vitro permeation experiments employing Franz diffusion cells apparatus. The standard enhancers Azone and THG were used to compare penetration enhancing effect of the enhancers. Results: It was revealed that DIMDOL could effectively enhance the permeability of both the drugs by 18.60 and 73.19 folds across the skin used with a lag time of 3.35 and 1.20 h, respectively. The newly synthesized derivative was found to significantly increase the partition coefficient and diffusion coefficient values. Conclusion: The results obtained suggest that DIMDOL can more effectively enhance the permeation of these model drugs, expectedly by affecting the stratum corneum and interacting with both lipid-rich layers and keratin-rich layers of the excised rat skin.
The purpose of the research is to evaluate Sterculiaurens gum as a carrier for oral colon targeted drug delivery system. Sterculia gum has been reported to have wide pharmaceutical applications such as tablet binder, disintegrant, gelling agent and as a controlled release polymer, but it has not been exploited as colon targeting carrier. For evaluation as a carrier for colonic delivery of drugs characterization of gum was done. Microflora degradation studies of gum were conducted in phosphate buffer solution (PBS) pH 7.4 containing rat caecal content under anaerobic environment. Solubility, swelling index, viscosity and pH of the polymer solution were determined. Different formulation aspects considered were: gum concentration (10–40%), concentration of citric acid (10–30 %) on swelling index and in-vitro drug release. The results of the isothermal stress testing (IST) shows no degradation of samples of model drug, azathioprine, in the drug polymer mixture and the core tablet excipients. DSC and FT-IR study has proved the compatibility of the drug with Sterculia gum and other tablet excipients. Microflora degradation study revealed that Sterculia gum can be used as tablet excipient for drug release in the colonic region by utilizing the action of enterobacteria. Sterculia gum exhibits premature drug release in the upper GIT without enteric coating and may not reach to the colonic region. From the study, Sterculia gum as colon targeting carrier is possible via coating with chitosan/Eudragit mixed blend polymers which would provide acid as well as intestinal resistance; but undergo enzymatic degradation once it reaches the colon.
Ayurveda is a traditional and scholarly medical system practiced in South Asia since the Vedic period. It integrates science and philosophy to promote a healthy, happy and prosperous life. Ayurvedicbhasmas are classical formulations that contain non-toxic forms of metals and minerals, enriched with therapeutic metabolites. These bhasmas are produced through repeated trituration of metals and minerals with the extracts from potent Ayurvedic herbs, followed by intense heating at temperatures above 650 °C. The preparation process of bhasmas closely resemble top-down approach in nanoparticle synthesis, resulting in very fine calcined nano-powders. These powders are used effectively in Ayurvedic treatments for various ailments, particularly chronic diseases. Recent studies have highlighted that bhasmas possess antioxidant, anti-inflammatory, antibacterial, antiviral and antitumor properties and may serve as potential carriers for drug delivery. This paper aims to compare bhasma particles prepared by traditional and modern methods, explore the therapeutic benefits of different bhasmas, and investigate the nanomedicinal features of various Ayurvedicbhasmas.
The current uncontrollable outbreak of novel coronavirus (COVID-19) has unleashed severe global consequences in all aspects of life and society, bringing the whole world to a complete halt and has modeled significant threats to the global economy. The COVID-19 infection manifests with flu-like symptoms such as cough, cold, and fever resulting in acute respiratory distress syndrome (ARDS), lung dysfunction, and other systemic complications in critical patients are creating panic across the globe. However, the licensed vaccine has started to show up; some resulted in side effects that would limit its possibility in some circumstances as allergic personnel, for example. Moreover, the production and approval of new drugs is a very complicated process and takes a long time. On the other hand, stem cells have gone the extra mile and intensively investigated at preclinical and clinical studies in various degenerative diseases, including infectious ones. Stem cells are proposed as a broad-spectrum therapeutic agent, which may suppress the exaggerated immune response and promote endogenous repair by enhancing COVID-19 infected lung microenvironment. Also, stem cells have different application manners, either direct transplantation, exosome transplantation, or drug delivery of specific cytokines or nanoparticles with antiviral property by engineering stem cells. This review discusses and summarizes the possible emerging role of cell-based therapy, especially stem cell therapy, as an alternative promising therapeutic option for the treatment and control of novel COVID-19 and its potential role in tissue rejuvenation after COVID-19 infection.
Emergence of various nanoscale drug carrier platforms as Drug Delivery Systems (DDS) has revolutionized the field of medicine.Nonetheless, theside-effects due to non-specific distribution of anticancer therapeutics in normal, healthy tissues remain to be a prime pitfall in curing cancers. Therefore, to achieve a better therapeutic efficacy, the use of a target-specific delivery, combined with a stimuli-responsive nanocarrier system, particularly pH-sensitive nanosystems offer an attractive strategy. Targeted drug delivery through pH-sensitive nanosystems offer the potential to enhance the therapeutic index of anticancer agents, either by increasing the drug concentration in tumor cells and/or by decreasing the exposure in normal host tissues. Therefore, nanoscale-based drug delivery through pH-sensitive nanosystems seem to be a boon for treating gynaecological cancers (as well as other cancers) without side-effects or with least harm to normal healthy tissues.
Antibody phage display has become a useful technique for discovering and optimizing target-specific monoclonal antibodies suitable for many applications, including therapeutic ligands, which may act as direct pharmacological compounds or may be used as targeting ligands for controlled drug delivery. Recently, the D2-5-HT1A heteromer, which is formed by the dopamine D2 and serotonin 5-HT1A receptors has attracted attention as a potential target of antipsychotic drugs. Therefore, the aim of the study was to identify scFv monoclonal antibodies that are able to specifically recognize epitopes formed within the heteromer structure. Because both receptors are membrane proteins, it is important to conduct bio-panning experiments in the most natural conditions, in which the presented antigens (D2-5-HT1A heteromers) are in their native form and possibly in their best-preserved spatial structure. It has been shown here that phage display methodology can be successfully used in the preparation of monoclonal antibodies against dimers of membrane proteins. To separate phages specifically binding the D2-5-HT1A heteromer, the selection process using CHO+ cells with overexpression of both receptors was conducted. Phages that were bound to receptor monomers or other CHO-K1 cell surface proteins were eliminated as a result of negative selection by using CHO- cells expressing separate receptor monomers.
The chemical and structural similarities of calcium orthophosphates (abbreviated as CaPO4)to the mineral composition of natural bones and teeth have made them a good candidate for bone tissue engineering applications. Nowadays, a variety of natural or synthetic CaPO4-based biomaterials is produced and has been extensively used for dental and orthopedic applications. Despite their inherent brittleness, CaPO4 materials possess several appealing characteristics as scaffold materials. Namely, their biocompatibility and variable stoichiometry, thus surface charge density, functionality and dissolution properties, make them suitable for both drug and growth factor delivery. Therefore, CaPO4, especially hydroxyapatite (HA) and tricalcium phosphates (TCPs), have attracted a significant interest in simultaneous use as bone grafts and drug delivery vehicles. Namely, CaPO4-based three-dimensional (3D) scaffolds and/or carriers have been designed to induce bone formation and vascularization. These scaffolds are usually porous and harbor various types of drugs, biologically active molecules and/or cells. Over the past few decades, their application as bone grafts in combination with stem cells has gained much importance. This review discusses the source, manufacturing methods and advantages of using CaPO4 scaffolds for bone tissue engineering applications. Perspective future applications comprise drug delivery and tissue engineering purposes.
Silver nanoparticles (Ag-NPs) are versatile materials with a broad range of applications in various fields such as cancer therapy, drug delivery. In this work, cytotoxic and apoptotic activities of silver nanoparticles was evaluation against lung (A549) and colon (HT-29) cell lines. The cytotoxic activity of nanoparticles was performed by MTT assay, while their apoptotic activity was tested through TUNEL method. The results of MTT of A549 have illustrate that fifty percent of cells destruction in concentrations more than 250 µg/ml of Ag-NPs. Apoptotic results of nanoparticles have shown more than fifty percent of apoptosis on A549 cell line. HT-29 display full apoptosis at concentrations more than 500 µg/ml. It seems that synthesized Ag-NPs by using P. farcta extract can be candidate as anti-cancer agent in treatment many cancers through creating or discovering new drug forms
Up till now, chitosan has confirmed its versatile application in skin, cartilage and bone tissue engineering, as well as in drug delivery applications. This study is focused on enzymatic degradation of porous chitosan structures usually designed for mentioned purposes. In vitro degradation was monitored during four weeks of incubation at physiological temperature and in two different media, phosphate buffer saline solution and water. The scaffolds were characterised before and after enzymatic degradation using scanning electron microscopy and infrared spectroscopy with Fourier transformations (FTIR). According to the gravimetric analysis, higher weight loss of chitosan scaffolds was observed in buffered medium with respect to the water. The results implied that the total weight loss obtained in buffer involves physical dissolution of chitosan and lysozyme cleavage of glycoside bond. Importantly, FTIR identification of chitosan scaffolds after enzymatic degradation indicated the absence of lysozyme activity in water, indicating that weight loss is a result of the chitosan dissolution. This finding greatly impacts design of degradation experiments and characterisation of degradation behaviour of chitosan-based materials utilised as implants or drug delivery systems.
Gold nanorods (GNRs) are plasmonic nanostructures by virtue of their size-dependent optical properties, offer a bionanotechnology platform in areas of bioimaging, drug delivery etc for disease diagnosis, prognosis, and therapy. GNRs are more sensitive to changes in local environments, and offer strong scattering and absorption efficiencies thus providing opportunities to integrate multiple imaging modes and therapeutic strategies. The hydrodynamic size of these GNR under physiological condition is <100 nm, making them ideal as intracellular delivery agents. RNA interference using small inhibitory RNA (siRNA) has become a powerful tool to downregulate mRNA levels by cellular nucleases that become activated when a sequence homology between the siRNA and a respective mRNA molecule is detected. siRNA is used to silence genes involved in the pathogenesis of various diseases and holds a promising option for the development of novel therapeutic strategies in neurological dysregulation such as that observed in drug addiction. However, a major challenge in gene therapy continues to be effective delivery of siRNA and its sustained release at targeted sites. Previously, we have shown the GNR coated with poly (diallyldimethyl ammoniumchloride) (GNR-PDDAC) electrostatically complexed to the dopamine- and cAMP-regulated neuronal phosphoprotein (DARPP-32) siRNA forming a GNR-nanoplex that was able to effectively silence the DARPP-32 gene expression in dopaminergic neuronal (DAN) cell cultures in- vitro. The current report, explores if modification of the surface coating properties of the GNRs with different surface coatings namely, amino terminated polyethylene glycol (GNR-PEG), polyethyleneimine (GNR-PEI) and Chitosan (GNR-CIT) alters their stability, cytotoxicity and DARPP-32 gene silencing efficiency in-vitro dopaminergic neuronal (DAN) cell cultures with the goal of determining the most suitable surface coating for the GNR that would provide a GNR-nanoplex with the most stability, least cytotoxicity and most efficacious gene silencing.