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► We investigate the efficacy of nanostructured lipid carrier over solid lipid nanoparticles for simvastatin. ► We utilize Pareto charts and response surface plots to identify ...optimized formulation. ► Optimized NLC revealed 2.29 folds increase in bioavailability as compared to SLNs.
Nanostructured lipid carrier (NLC) system of simvastatin was investigated for improvement in release, pharmacokinetics and biodistribution over its solid lipid nanoparticles (SLN). The NLC formulations prepared by solvent injection technique were optimized by 2
3 full factorial design. Optimized NLC was deduced on the basis of dependent variables that were analyzed using Design expert 8.0.2
® software (Stat Ease, Inc., USA). Pareto charts and response surface plots were utilized to study the effect of variables on the response parameters. The optimized NLC was a suspension of nanosized homogeneous particles with significantly higher entrapment efficiency (>90%) and lower recrystallization properties (
p
<
0.01) than SLNs. The pharmacokinetic parameters of Tc
99 labeled optimized NLC in mice, obtained using Quickcal software (Plexus, India) revealed 4.8 folds increase in bioavailability as compared to simvastatin suspension and 2.29 folds as compared to SLNs. Biodistribution study revealed preferential accumulation of NLC in the liver and this is advantageous because liver is the target organ for simvastatin. IVIVC studies demonstrated level A correlation between
in vitro release and percent drug absorbed. This investigation demonstrated the superiority of NLC over SLN for improved oral delivery and it was deduced that the liquid lipid, oleic acid was the principal formulation factor responsible for the improvement in characteristics, pharmacokinetics and biodistribution of NLCs.
The work was aimed to validate the gastroretentive potential of microsponges via optimization of targeted floating curcumin microsponges for improved site specific absorption for gastric cancer ...Modified quasi emulsion solvent diffusion method was used to formulate microsponges using 32 full factorial design. The effect of different levels of ethyl cellulose and polyvinyl alcohol concentration, selected as independent variables was determined on the % entrapment efficiency, % buoyancy and % cumulative drug release. Modified rosette rise apparatus was used for in vitro release and the release data best fitted Higuchi's model and mechanism of drug release was diffusion (n). The optimized formulation (MS5) demonstrated favourable % entrapment efficiency (90.7±1.7), % buoyancy (82.0±2.0) and % cumulative drug release (85.2±1.07) with maximum desirability factor of 0.816. SEM revealed spherical and porous microsponges. DSC confirmed molecular dispersion of the drug in the microsponges polymeric matrix. DRIFT revealed no chemical interaction between the drug and polymer used. The in vitro permeation of curcumin through gastric mucin gel layer affirmed the capability of microsponges to deliver drug across mucin r and reach the target site to treat gastric cancer. Anticancer oral dose of microsponges was calculated as 50mg by cytotoxicity assay in human cancer cell line KB. The pharmacokinetic evaluation of MS5 in rabbits revealed 10-fold increase in bioavailability as compared to native curcumin, demonstrated the superiority of microsponges over native curcumin as gastro retentive drug delivery system. This study presents a new approach based on floating ability of microsponges for treatment of gastric cancer.
Among heterocyclic compounds, quinoline scaffold has become an important construction motif for the development of new drugs. Quinoline and its derivatives possess many types of biological activities ...and have been reported to show significant anticancer activity. Quinoline compounds play an important role in anticancer drug development as they have shown excellent results through different mechanism of action such as growth inhibitors by cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration and modulation. A number of quinoline derivatives have been reported till date for their anticancer activity. The present review, summarizes various mono-, di-, tri-, tetra- and heterocyclic substituent quinoline derivatives with potential anticancer activity. Their mechanism of action and possible structure activity relationship has also been discussed.
A particular biological process known as wound healing is connected to the overall phenomena of growth and tissue regeneration. Several cellular and matrix elements work together to restore the ...integrity of injured tissue. The goal of the present review paper focused on the physiology of wound healing, medications used to treat wound healing, and local drug delivery systems for possible skin wound therapy. The capacity of the skin to heal a wound is the result of a highly intricate process that involves several different processes, such as vascular response, blood coagulation, fibrin network creation, re-epithelialisation, collagen maturation, and connective tissue remodelling. Wound healing may be controlled with topical antiseptics, topical antibiotics, herbal remedies, and cellular initiators. In order to effectively eradicate infections and shorten the healing process, contemporary antimicrobial treatments that include antibiotics or antiseptics must be investigated. A variety of delivery systems were described, including innovative delivery systems, hydrogels, microspheres, gold and silver nanoparticles, vesicles, emulsifying systems, nanofibres, artificial dressings, three-dimensional printed skin replacements, dendrimers and carbon nanotubes. It may be inferred that enhanced local delivery methods might be used to provide wound healing agents for faster healing of skin wounds.
Abstract This project aimed at developing nanovesicles of econazole nitrate (EN) and formulating them as a suitable dermatological gel for improved therapeutic efficacy, better dispersity, and good ...storage stability. Ethosomes were prepared by cold method and evaluated for the mean diameter, surface charge, and entrapment efficiency. Optimized ethosomes with vesicle size and entrapment efficiency of 202.85 ± 5.10 nm and 81.05 ± 0.13%, respectively, were formulated as Carbopol 934 NF gels with varied permeation enhancers (G1–G7), and compared with liposomal and hydroethanolic gels. The pharmacotechnical evaluation of gels demonstrated G6 with a flux rate of 0.46 ± 0.22 μg/cm2 hr 1/ 2 as the best formulation that was able to exhibit controlled release of EN for 12 hours across rat skin, and percent drug diffused from ethosomes was nearly twofold higher than liposomal and hydroethanolic gels. Confocal laser scanning microscopy demonstrated drug permeation as far as the last layer of epidermis (stratum basale). Stability profile of the prepared system assessed for 180 days revealed very low aggregation and insignificant growth in vesicular size. The results collectively suggest that because of the controlled drug release, better antifungal activity, and good storage stability, EN ethosomal gel has tremendous potential to serve as a topical delivery system. From the Clinical Editor Ethosomal gel of econazole nitrate was found to have outstanding potential to serve as a topical delivery system, enabling controlled drug release, providing better antifungal activity, and good storage stability.
This review brings forth the potential of thiazole derivatives for their anticancer activities. The emphasis is placed on the structural diversity of thiazole derivatives, responsible for their ...specific anticancer activity. Multiple classes of thiazole derivatives such as Schiff base, mono-, di-, tri-, and heterocyclic substituents that possess anticancer activity have been exemplified. Molecular modelling of compounds that predicts enhanced anticancer activity of the modified structures has also been elaborated in the review. Significant advancements in synthetic chemistry related to cytotoxicity can now better position the drug discovery team to undertake thiazoles as valuable leads. The beneficial thiazole derivatives possessing anticancer activity will reignite the interest of medicinal chemists in thiazole and their derivatives.
Background: Non-invasive and patient-friendly nose-to-brain pathway is the best-suited route for brain delivery of therapeutics as it bypasses the blood–brain barrier. The intranasal pathway ...(olfactory and trigeminal nerves) allows the entry of various bioactive agents, delivers a wide array of hydrophilic and hydrophobic drugs, and circumvents the hepatic first-pass effect, thus targeting neurological diseases in both humans and animals. The olfactory and trigeminal nerves make a bridge between the highly vascularised nasal cavity and brain tissues for the permeation and distribution, thus presenting a direct pathway for the entry of therapeutics into the brain. Materials: This review portrays insight into recent research reports (spanning the last five years) on the nanoemulsions developed for nose-to-brain delivery of actives for the management of a myriad of neurological disorders, namely, Parkinson’s disease, Alzheimer’s, epilepsy, depression, schizophrenia, cerebral ischemia and brain tumours. The information and data are collected and compiled from more than one hundred Scopus- and PubMed-indexed articles. Conclusions: The olfactory and trigeminal pathways facilitate better biodistribution and bypass BBB issues and, thus, pose as a possible alternative route for the delivery of hydrophobic, poor absorption and enzyme degradative therapeutics. Exploring these virtues, intranasal nanoemulsions have proven to be active, non-invasiveand safe brain-targeting cargos for the alleviation of the brain and other neurodegenerative disorders.
Anticancer drugs in monotherapy are ineffective to treat various kinds of cancer due to the heterogeneous nature of cancer. Moreover, available anticancer drugs possessed various hurdles, such as ...drug resistance, insensitivity of cancer cells to drugs, adverse effects and patient inconveniences. Hence, plant-based phytochemicals could be a better substitute for conventional chemotherapy for treatment of cancer due to various properties: lesser adverse effects, action via multiple pathways, economical, etc. Various preclinical studies have demonstrated that a combination of phytochemicals with conventional anticancer drugs is more efficacious than phytochemicals individually to treat cancer because plant-derived compounds have lower anticancer efficacy than conventional anticancer drugs. Moreover, phytochemicals suffer from poor aqueous solubility and reduced bioavailability, which must be resolved for efficacious treatment of cancer. Therefore, nanotechnology-based novel carriers are employed for codelivery of phytochemicals and conventional anticancer drugs for better treatment of cancer. These novel carriers include nanoemulsion, nanosuspension, nanostructured lipid carriers, solid lipid nanoparticles, polymeric nanoparticles, polymeric micelles, dendrimers, metallic nanoparticles, carbon nanotubes that provide various benefits of improved solubility, reduced adverse effects, higher efficacy, reduced dose, improved dosing frequency, reduced drug resistance, improved bioavailability and higher patient compliance. This review summarizes various phytochemicals employed in treatment of cancer, combination therapy of phytochemicals with anticancer drugs and various nanotechnology-based carriers to deliver the combination therapy in treatment of cancer.
The application of metallic nanoparticles as a novel therapeutic tool has significant potential to facilitate the treatment and diagnosis of mitochondria-based disorders. Recently, subcellular ...mitochondria have been trialed to cure pathologies that depend on their dysfunction. Nanoparticles made from metals and their oxides (including gold, iron, silver, platinum, zinc oxide, and titanium dioxide) have unique modi operandi that can competently rectify mitochondrial disorders.
This review presents insight into the recent research reports on exposure to a myriad of metallic nanoparticles that can alter the dynamic ultrastructure of mitochondria (via altering metabolic homeostasis), as well as pause ATP production, and trigger oxidative stress. The facts and figures have been compiled from more than a hundred PubMed, Web of Science, and Scopus indexed articles that describe the essential functions of mitochondria for the management of human diseases.
Nanoengineered metals and their oxide nanoparticles are targeted at the mitochondrial architecture that partakes in the management of a myriad of health issues, including different cancers. These nanosystems not only act as antioxidants but are also fabricated for the delivery of chemotherapeutic agents. However, the biocompatibility, safety, and efficacy of using metal nanoparticles is contested among researchers, which will be discussed further in this review.
Improvement of oral bioavailability through enhancement of dissolution for poorly soluble drugs has been a very promising approach. Recently, mesoporous silica based molecular sieves have ...demonstrated excellent properties to enhance the dissolution velocity of poorly water-soluble drugs.
Current research in this area is focused on investigating the factors influencing the drug release from these carriers, the kinetics of drug release and manufacturing approaches to scale-up production for commercial manufacture.
This comprehensive review provides an overview of different methods adopted for synthesis of mesoporous materials, influence of processing factors on properties of these materials and drug loading methods. The drug release kinetics from mesoporous silica systems, the manufacturability and stability of these formulations are reviewed. Finally, the safety and biocompatibility issues related to these silica based materials are discussed.
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