Nanotechnology in drug delivery: the need for more cell culture based studies in screening

Advances in biomedical science are leading to upsurge synthesis of nanodelivery systems for drug delivery. The systems were characterized by controlled, targeted and sustained drug delivery ability. Humans are the target of these systems, hence, animals whose systems resembles humans were used to predict outcome. Thus, increasing costs in money and time, plus ethical concerns over animal usage. However, with consideration and planning in experimental conditions, in vitro pharmacological studies of the nanodelivery can mimic the in vivo system. This can function as a simple method to investigate the effect of such materials without endangering animals especially at screening phase

Hepatoprotective nature of phytoextracts against hepatotoxin induced animal models: a review

Liver is the largest vital organ in human body and plays a major role in various metabolism and excretion of xenobiotics within the body. Liver dysfunction is a foremost health problem that challenges not only health care professionals but also the pharmaceutical industry as more than 900 drugs are implicated in case of liver injury. Hepatotoxicity is caused by various toxic substances and certain pharmaceutical drugs which produce liver injury such as-carbon tetrachloride, thioacetamide, high doses of acetaminophen, anti-tubercular drugs, few chemotherapeutic agents etc. The existing modern synthetic drugs to treat liver disorders in this condition also cause furthermore liver damage/complications. Therefore, many herbal drugs from natural origin have become increasingly popular and their use is wide spread. These herbal medicines have been used in the treatment of liver diseases for a long time because of their antioxidants properties and tissue protective nature. Extensive researches have been carried out on medicinal plants; however, only few herbal plants have attracted the interest of researchers, to evaluate them for better protective/therapeutic agents for hepatoprotective against chemical induced liver toxicity. Various preclinical investigations have proved that the efficacy of medicinally important plants in the treatment of liver diseases/disorders. Hence, this article provided valuable evidence to the knowledge of investigated medicinal plants; especially those medicinal plants are suitable for hepatoprotective and therapeutic nature against liver toxicity

Protective nature of mangiferin on oxidative stress and antioxidant status in tissues of streptozotocin-induced diabetic rats

Oxidative stress plays an important role in the progression of diabetes complications. The aim of the present study was to investigate the beneficial effect of oral administration of mangiferin in streptozotocin (STZ)-induced diabetic rats by measuring the oxidative indicators in liver and kidney as well as the ameliorative properties. Administration of mangiferin to diabetic rats significantly decreased blood glucose and increased plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and level of reduced glutathione (GSH) were significantly (P < 0.05) decreased while increases in the levels of lipidperoxidation (LPO) markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with mangiferin (40 mg/kg b.wt/day) for a period of 30 days showed significant ameliorative effects on all the biochemical and oxidative parameters studied. Diabetic rats treated with mangiferin restored almost normal architecture of liver and kidney tissues, which was confirmed by histopathological examination. These results indicated that mangiferin has potential ameliorative effects in addition to its antidiabetic effect in experimentally induced diabetic rats

Identification of bioactive candidate compounds responsible for oxidative challenge from hydro-ethanolic extract of Moringa oleifera leaves.

Free radicals trigger chain reaction and inflict damage to the cells and its components, which in turn ultimately interrupts their biological activities. To prevent free radical damage, together with an endogenous antioxidant system, an exogenous supply of antioxidant components to the body in the form of functional food or nutritional diet helps undeniably. Research conducted by the Natl. Inst. of Health claimed that Moringa oleifera Lam possess the highest antioxidant content among various natural food sources based on an oxygen radical absorbent capacity assay. In this study, a 90% (ethanol:distilled water—90:10) gradient solvent was identified as one of the best gradient solvents for the effectual extraction of bioactive components from M. oleifera leaves. This finding was confirmed by various antioxidant assays, including radical scavenging activity (that is, 1, 1-diphenyl-2-picrylhydrazyl, H2O2, and NO radical scavenging assay) and total antioxidant capacity (that is, ferric reducing antioxidant power and molybdenum assay). High-performance liquid chromatography (HPLC) fingerprints of the 90% gradient extract visually showed few specific peaks, which on further analysis, using HPLC–DAD–ESI–MS, were identified as flavonoids and their derivatives. Despite commonly reported flavonoids, that is, kaempferol and quercetin, we report here for the 1st time the presence of multiflorin-B and apigenin in M. oleifera leaves. These findings might help researchers to further scrutinize this high activity exhibiting gradient extract and its bio-active candidates for fruitful clinical/translational investigations

In vitro anti-cancer effect of layered double hydroxide-chlorogenic acid nanoparticles as drug delivery system

Layered double hydroxides (LDHs) have obtained significant attention as nano-sized carriers for therapeutic and bio-active molecules. LDH nanoparticles are competent for drug delivery purposes due to their numerous advantageous properties such as unique structure, high anionic exchangeability and solubility in acidic media which give rise to the controlled release of intercalated molecules. Hence, the aim of this study is to investigate the properties of newly constructed drug delivery system consisting a natural compound, chlorogenic acid (CA) intercalated into Zn/Al-LDH interlayers for the formation of the nanocomposite. Structural and physical properties of chlorogenic acid intercalated into Zn/Al-LDH (CA-Zn/Al-LDH) were determined by X-ray diffraction, field emission scanning and transmission electron microscope. Loading efficiency of CA in between the interlayers of Zn/Al-LDH was investigated using a UV-Vis spectrophotometer. Subsequently for in vitro work, the anti-cancer properties of CA-Zn/Al-LDH nanocomposite on various cancer and normal cell lines were carried out using 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyl bromide (MTT) reduction assay. Half-maximal inhibitory concentrations of CA-Zn/Al-LDH in all the cell lines was found to be ranged from 0-50 μg/L, determined after 24, 48 and 72 h. To justify their efficacy, apoptosis induction and clonogenic inhibition of chlorogenic acid-LDH nanocomposite were observed and analyzed microscopically. The preliminary result of this study may offer valuable primary information towards the development of potential nanodrugs for cancer therapy

Mangiferin from Salacia chinensis prevents oxidative stress and protects pancreatic β-cells in streptozotocin-induced diabetic rats

Oxidative stress in diabetic tissues is a consequence of free radical accumulation with concurrently impaired natural antioxidants status and results in oxidative tissue damage. The present study investigated the protective effects of mangiferin against pancreatic β-cell damage and on the antioxidant defense systems in streptozotocin (STZ)-induced diabetic rats. Diabetes was experimentally induced by a single intraperitoneal injection of STZ. Oxidative stress biomarkers such as tissue malondialdehyde, hydroperoxides, reduced glutathione (GSH) content, and nonenzymatic antioxidants were measured. Biochemical observations were further substantiated with histological examination and ultrastructural studies in the pancreas of diabetic, glibenclamide and mangiferin-treated diabetic rats (dosage of 40 mg/kg body weight daily for 30 days). Oral administration of mangiferin and glibenclamide to diabetic rats significantly decreased the level of blood glucose and increased levels of insulin. Additionally, mangiferin treatment significantly modulated the pancreatic nonenzymatic antioxidants status (vitamin C, vitamin E, ceruloplasmin, and reduced GSH content) and other oxidative stress biomarkers. The histoarchitecture of diabetic rats showed degenerated pancreas with lower β-cell counts, but mangiferin treatment effectively regenerated insulin secreting islet cells. The electron microscopic study revealed damaged nuclear envelope and mitochondria and fewer secretory granules in pancreas of diabetic rats; however, mangiferin treatment nearly normalized pancreatic architecture. The present findings suggest that mangiferin treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress and protecting against pancreatic β-cell damage, which may be attributable to its antioxidative properties

Topical treatments with blue-green algae aqueous extract promote healing of diabetic wound

Blue-green algae or scientifically known as Spirulinaplatensis, is gaining more attention and becoming a health food worldwide due to its nutritional and medicinal properties. Their roles as antioxidant, antiviral, anticancer and antidiabetic have been well established. The aim of this study is to examine the efficacy of aqueous extract of Spirulinaplatensis on wound repair in streptozotocin–nicotinamide-induced diabetic rats. Open excision wounds were made on the back of rats 5 days after diabetes induction. Aqueous extract at a dosage of 100 and 200 mg/kg body weight was reconstituted in 100 μl of phosphate buffered saline and applied topically once every 2 days up to 14 days for the treated wounds. Animals in normal and diabetic control groups were left untreated. Wound areas were measured on day 0, 7 and 14 post-wounding. Wound size and percentage wound contraction were observed to heal much faster on diabetic wounds which received treatment of the extract. The findings demonstrate the beneficial effects of the topical application of blue-green-algae aqueous extract in the acceleration of diabetic wound healing in animal model

Arginine–chitosan- and arginine–polyethylene glycol-conjugated superparamagnetic nanoparticles: preparation, cytotoxicity and controlled-release

Iron oxide magnetic nanoparticles (MNPs) can be used in targeted drug delivery systems for localized cancer treatment. MNPs coated with biocompatible polymers are useful for delivering anticancer drugs. Iron oxide MNPs were synthesized via co-precipitation method then coated with either chitosan (CS) or polyethylene glycol (PEG) to form CS–MNPs and PEG–MNPs, respectively. Arginine (Arg) was loaded onto both coated nanoparticles to form Arg–CS–MNP and Arg–PEG–MNP nanocomposites. The X-ray diffraction results for the MNPs and the Arg–CS–MNP and Arg–PEG–MNPs nanocomposites indicated that the iron oxide contained pure magnetite. The amount of CS and PEG bound to the MNPs were estimated via thermogravimetric analysis and confirmed via Fourier transform infrared spectroscopy analysis. Arg loading was estimated using UV–vis measurements, which yielded values of 5.5% and 11% for the Arg–CS–MNP and Arg–PEG–MNP nanocomposites, respectively. The release profile of Arg from the nanocomposites followed a pseudo-second-order kinetic model. The cytotoxic effects of the MNPs, Arg–CS–MNPs, and Arg–PEG–MNPs were evaluated in human cervical carcinoma cells (HeLa), mouse embryonic fibroblast cells (3T3) and breast adenocarcinoma cells (MCF-7). The results indicate that the MNPs, Arg–CS–MNPs, and Arg–PEG–MNPs do not exhibit cytotoxicity toward 3T3 and HeLa cells. However, treatment of the MCF-7 cells with the Arg–CS–MNP and Arg–PEG–MNP nanocomposites reduced the cancer cell viability with IC50 values of 48.6 and 42.6 µg/mL, respectively, whereas the MNPs and free Arg did not affect the viability of the MCF-7 cells

Development of a controlled-release anti-parkinsonian nanodelivery system using levodopa as the active agent.

A new layered organic-inorganic nanocomposite material with an anti-parkinsonian active compound, L-3-(3,4-dihydroxyphenyl) alanine (levodopa), intercalated into the inorganic interlayers of a Zn/Al-layered double hydroxide (LDH) was synthesized using a direct coprecipitation method. The resulting nanocomposite was composed of the organic moiety, levodopa, sandwiched between Zn/Al-LDH inorganic interlayers. The basal spacing of the resulting nano-composite was 10.9 Å. The estimated loading of levodopa in the nanocomposite was approximately 16% (w/w). A Fourier transform infrared study showed that the absorption bands of the nanocomposite were characteristic of both levodopa and Zn/Al-LDH, which further confirmed intercalation, and that the intercalated organic moiety in the nanocomposite was more thermally stable than free levodopa. The resulting nanocomposite showed sustained-release properties, so can be used in a controlled-release formulation. Cytotoxicity analysis using an MTT assay also showed increased cell viability of 3T3 cells exposed to the newly synthesized nanocomposite compared with those exposed to pure levodopa after 72 hours of exposure