ethyl-cellulose and Hemolysis

Amphotericin B is a gold standard drug used in various fungal and parasitic infection treatment. Most of the marketed formulations are administered intravenously, but show dose-dependent adverse effects i.e., nephrotoxicity and hemolysis. Oral route eliminates the toxic concern but exhibits poor bioavailability. Therefore, ethylcellulose nanoparticles (EC-NPs) have been used for magnified oral delivery of AmB, where EC provides gastrointestinal stability. These nanoparticles were synthesized by high-pressure emulsification solvent evaporation (HPESE) method and evaluated for in vitro and in vivo studies. This method yields small, monodisperse AmB-EC-NPs along with smooth surface morphology and improved encapsulation efficiency. The developed formulation showed a sustained release pattern following Higuchi diffusion kinetics along with gastric and storage stability. Aggregation study revealed that AmB was present in its monomeric form inside the biocompatible EC matrix. The antifungal result demonstrated that the MIC of AmB-EC-NPs was reduced ∼1/3rd than AmB and Fungizone® at 24 h whereas it was observed ∼1/8th at 48 h. in vivo pharmacokinetic analysis demonstrated 1.3-fold higher AUC than Fungizone® even at a 4.5-time lesser dose via the oral route and a ∼15-fold rise in the bioavailability in contrast to the native AmB. The hemolytic study revealed that the developed formulation exhibited 8-fold lesser hemolysis than Fungizone®. Furthermore, the biosafety profile of AmB-EC-NPs was ensured by the significantly lesser level of blood urea nitrogen and plasma creatinine along with the normal pattern of renal tubules in comparison to AmB and Fungizone®. In conclusion, the results stipulated that the AmB-EC-NPs could be effective, viable and a better alternative to currently existing iv formulations, for magnified oral delivery of AmB in the treatment of fungal infection without associated adverse effects.

Topics: Administration, Oral; Amphotericin B; Animals; Antifungal Agents; Biological Availability; Candida albicans; Cellulose; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Liberation; Drug Stability; Hemolysis; Kidney Tubules; Male; Nanoparticles; Rats, Wistar

To our knowledge, no such polymeric nanoparticle formulation toxicity study has been reported for oral use. The oral route of drug administration is generally preferred because of its versatility, safety and relative patient comfort. Hence, there is an outstanding need of research for polymeric nanoparticles to find whether they are stable for prolonged shelf life, and yet have no toxicity when administered orally. The main objective of this study is to assess the safety of Glipizide (GZ) loaded polymeric nanoparticle systematically and to observe the toxic effects of nanoparticles on the functions of various tissues and organs in rats. The rats were randomly divided into 7 groups (6 in each group); viz. one normal control group (received saline), two groups (1:2 and 1:5 ratio of GZ-Chitosan nanoparticle), two groups (1:2 and 1:5 ratio of GZ-Poly(methyl methacrylate) nanoparticle) and two groups (1:2 and 1:5 ratio of GZ-Ethyl Cellulose nanoparticle). After 30 days of nanoparticle administration, the blood haematology and biochemistry were investigated, along with the histopathological examination. The rats did not show any significant changes in all the parameters studied and the results clearly evidenced its safety. All formulations showed in vitro haemolytic activity less than 5%. Conclusion drawn from the present study is that the polymeric nanoparticles may be a suitable device for safe oral administration. A rigorous safety of these nanoparticles would enable their use in the field of diabetic therapy.

Topics: Administration, Oral; Animals; Cellulose; Chitosan; Female; Glipizide; Hemolysis; Hypoglycemic Agents; Microscopy, Electron, Scanning; Nanocapsules; Nanotechnology; Particle Size; Polymethyl Methacrylate; Rats; Rats, Wistar

The present study was designed to assess and compare with a range of surfactant-coated, nimesulide-free, and nimesulide-loaded ethylcellulose/methylcellulose (EC/MC) nanoparticles that were prepared by varying drug concentration (ED/MD), polymer concentration (EP/MP), and surfactant concentration (ES/MS). EC/MC nanoparticles prepared by desolvation method produced discrete particles and they were characterized by SEM, AFM, and FTIR studies. The particles mean size diameter (nm) ranged from 244 to 1056 nm and 1065 to 1710 nm for EC and MC nanoparticles, respectively. Studies on drug: polymer ratio showed a linear relationship between drug concentration and percentage of loading in nanoparticles. The encapsulation efficiency decreased with the increase of nimesulide concentration with respect to polymer concentration. Encapsulation efficiency of drug-loaded nanoparticles was varied between 32.8% and 64.9%. The in vitro release of drug-loaded nanoparticles was found to be a first order. This was significantly increased in EC nanoparticles (95.50%) in comparison with MC nanoparticles (95.12%) after 12 h in 24 h long study. Nimesulide release from EC nanoparticles was much slower at slightly alkaline pH 7.4. The in vitro hemolysis tests of nanoparticles were carried out to ascertain the hemocompatibility and shown to be insignificant for EC nanoparticles. In comparison, ES4 from EC formulations with nimesulide was found to be promising with slow and sustained drug release.

Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Cellulose; Drug Carriers; Hemolysis; Humans; Methylcellulose; Microscopy, Atomic Force; Nanoparticles; Particle Size; Spectroscopy, Fourier Transform Infrared; Sulfonamides