ABSTRACT
Biocompatible gold nanoparticles were synthesized by using a naturally occurring gum--Gellan Gum--as a capping and reducing agent. These were further conjugated with sophorolipids which again were accessed through a biochemical transformation of a fatty acid. The cellular uptake of sophorolipid-conjugated gellan gum reduced gold nanoparticles and their cytotoxicity on human glioma cell line LN-229 and human glioma stem cell line HNGC-2 were investigated. Quite surprisingly even the simple sophorolipid-conjugated gellan gum reduced/capped gold nanoparticles showed greater efficacy in killing the glioma cell lines and, gratifyingly, the glioma stem cell lines also. The cytotoxic effects became more prominent once the anti cancer drug doxorubicin hydrochloride was also conjugated to these gold nanoparticles.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Doxorubicin/administration & dosage , Glioma/drug therapy , Gold/chemistry , Metal Nanoparticles/chemistry , Polysaccharides, Bacterial/chemistry , Apoptosis , Cell Line, Tumor , Drug Carriers/chemistry , Humans , Polysaccharides, Bacterial/toxicityABSTRACT
Currently gold nanoparticles are being explored for drug delivery and other biomedical applications; therefore it is necessary to study the fate of such nanoparticles inside the body. The objective of the present study was to investigate the cellular uptake and toxicity of the gold nanoparticles synthesized using a microbial polysaccharide, gellan gum, as a capping and reducing agent. The cellular uptake of gold nanoparticles was studied on mouse embryonic fibroblast cells, NIH3T3 and human glioma cell line, LN-229. The cellular uptake study indicated that the gellan gum-reduced gold nanoparticles were located in cancer cells (LN-229) while no uptake was observed in normal mouse embryonic fibroblast cells (NIH3T3). The toxicity of the gold nanoparticles was evaluated by carrying out subacute 28 day oral toxicity studies in rats. Subacute administration of gum-reduced gold nanoparticles to the rats did not show any hematological or biochemical abnormalities. The weight and normal architecture of various organs did not change compared with control. The current findings, while establishing the specific uptake of nanoparticles into cancerous cells, also demonstrates that the gellan gum-reduced gold nanoparticles are devoid of toxicity in animals following oral administration.
Subject(s)
Gold Compounds/toxicity , Metal Nanoparticles/toxicity , Administration, Oral , Animals , Biocompatible Materials , Body Weight/drug effects , Cell Line, Tumor , Clinical Chemistry Tests , Culture Media/chemistry , Eating/drug effects , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Glioma/drug therapy , Glioma/metabolism , Gold Compounds/chemistry , Gold Compounds/metabolism , Hematologic Tests , Humans , Male , Metal Nanoparticles/ultrastructure , Mice , NIH 3T3 Cells , Oxidation-Reduction , Polysaccharides, Bacterial/chemistry , Rats , Rats, Wistar , Toxicity TestsABSTRACT
To overcome many challenges associated with antiretroviral drug therapy, novel drug delivery systems present an opportunity for formulation scientists to improve the management of patients with HIV/AIDS. The purpose of this study was to prepare a transdermal delivery system for zidovudine using different penetration enhancers incorporated in carbopol 971P gel and to evaluate the same for rheology, percent drug content, drug deposition, in vitro, ex vivo, and in vivo permeation across rat skin. The rheology studies indicated that 1% w/w carbopol gel had a higher linear viscoelastic region, good creep recovery, and desirable viscosity. Among all gel formulations, gel containing cineole and menthol as penetration enhancers attained a steady-state flux of 5.9 mg/cm(2)/h and 5.4 mg/cm(2)/h of zidovudine, respectively, leading to plasma concentration in the therapeutic range. The drug deposition was also found to be highest in the case of gel containing cineole and menthol as penetration enhancers. The results indicated a linear relationship between in vitro flux and in vivo bioavailability of zidovudine transdermal gel.
Subject(s)
Skin Absorption , Zidovudine , Administration, Cutaneous , Animals , Chemistry, Pharmaceutical , Gels/metabolism , Humans , Skin/drug effects , Zidovudine/metabolismABSTRACT
The purpose of this study was to improve the solubility and dissolution rate of carvedilol by forming a ternary complex with beta-cyclodextrin and citric acid and to formulate its mouth-dissolving tablets. The rationale for preparing mouth-dissolving tablet of carvedilol was to make the drug available in a soluble form in the mouth, which would facilitate its absorption from the buccal cavity. This would help to overcome its first-pass metabolism and thereby improve bioavailability. Phase solubility studies revealed the ability of beta-cyclodextrin and citric acid to complex with carvedilol and significantly increase its solubility. Ternary complexation of carvedilol was carried out with beta-cyclodextrin and citric acid by physical mixing, kneading and spray drying methods and the prepared complexes were characterized by Fourier transform infra red spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and complexation efficiency. The complex obtained by the spray drying method resulted in highest complexation efficiency and a 110-fold increase in the solubility of carvedilol. The mouth-dissolving tablets formulated using the spray dried complex with suitable excipients showed 100 % dissolution within five minutes. Accelerated stability studies of mouth-dissolving tablets carried out as per ICH guidelines revealed that the tablets were stable.
Subject(s)
Adrenergic beta-Antagonists/chemistry , Carbazoles/chemistry , Citric Acid/chemistry , Excipients/chemistry , Propanolamines/chemistry , beta-Cyclodextrins/chemistry , Administration, Buccal , Adrenergic beta-Antagonists/administration & dosage , Calorimetry, Differential Scanning , Carbazoles/administration & dosage , Carvedilol , Chemistry, Pharmaceutical , Crystallography, X-Ray , Drug Stability , Kinetics , Microscopy, Electron, Scanning , Powder Diffraction , Propanolamines/administration & dosage , Solubility , Spectroscopy, Fourier Transform Infrared , Tablets , Technology, Pharmaceutical/methodsABSTRACT
The objective of the present study was to evaluate the oral toxicity of chitosan reduced gold nanoparticles so as to demonstrate its applicability for drug delivery application. Acute oral toxicity studies in female rats documented no deaths or treatment related complications. The LD50 value of gold nanoparticles was found to be greater than 2000 mg/kg. In case of sub-acute oral toxicity studies, gold nanoparticles were administered orally to male and female rats for a period of 28-days. At the end of study blood samples were collected for haematology and biochemical analysis. For histopathological analysis, organs of animals were weighed and processed for examination. All animals survived the duration of the study, with no significant changes in clinical signs, body weight, food consumption, hematological parameters, organ weights and histopathological findings. These studies establish that chitosan reduced gold nanoparticles produced no treatment related toxicity in rats following oral administration, thus can be exploited for potential therapeutic applications.
Subject(s)
Chitosan/toxicity , Drug Carriers/toxicity , Drug-Related Side Effects and Adverse Reactions/chemically induced , Gold/toxicity , Nanoparticles/toxicity , Animals , Dose-Response Relationship, Drug , Female , Lethal Dose 50 , Male , Materials Testing , Rats , Rats, Wistar , Survival RateABSTRACT
"Gellan Gum", widely used in food and confectionary industry as a thickening and gelling agent, has been employed as a reducing and stabilizing agent for the synthesis of gold nanoparticles. These nanoparticles display greater stability to electrolyte addition and pH changes relative to the traditional citrate and borohydride reduced nanoparticles. Subsequently these have been used to load anthracycline ring antibiotic doxorubicin hydrochloride. The drug loaded on these nanoparticles showed enhanced cytotoxic effects on human glioma cell lines LN-18 and LN-229.
Subject(s)
Gold/chemistry , Metal Nanoparticles/chemistry , Polysaccharides, Bacterial/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Chemistry, Pharmaceutical , Doxorubicin/pharmacology , Humans , Hydrogen-Ion Concentration , Metal Nanoparticles/ultrastructure , Microscopy, Electron, Transmission , Molecular Structure , SpectrophotometryABSTRACT
Carvedilol a poorly water soluble drug undergoes extensive first pass metabolism, which reduces its bioavailability to 25-30%. Mouth dissolving tablets of Carvedilol were prepared with the purpose of delivering the drug directly into the systemic circulation and bypassing the hepatic first pass metabolism with a concomitant increase in bioavailability. The solubility of Carvedilol was improved by forming inclusion complex with cyclodextrin which was then further used for the formulation of mouth dissolving tablet. Differential scanning calorimetry and Infrared spectroscopy results indicated no incompatibilities between drug-excipient mixtures. Effect of three different superdisintegrants on disintegration was studied. The formulations were evaluated for drug content, content uniformity, friability, disintegration time and in-vitro dissolution. Tablets containing Carvedilol-beta-cyclodextrin complex exhibited good tablet properties, with 90% drug dissolved within 5 min. This demonstrated the effectiveness of using various superdisintegrants and Carvedilol-beta-cyclodextrin complex in formulation of mouth dissolving tablet.
