ABSTRACT
Mycobacterium tuberculosis, being the causative infectious agent, is the leading cause of death worldwide amongst the infectious disease. The low bioavailability of rifampicin (RIF), one of the vital constituent of antitubercular therapy, instigates an urge to develop nanocarrier, which can prevent its degradation in the acidic pH of the stomach. Solid lipid nanoparticles (SLNs) have been proven to be promising versatile platform for oral delivery of lipophilic drugs. Therefore, the current investigation demonstrates development of RIF-loaded solid lipid nanoparticles (RIF-SLNs) using high-pressure homogenization technique by employing a three-level, three-factor Box-Behnken design. Concentration of drug, concentration of emulsifier, and homogenization pressure were selected as an independent variables, and %drug loading (%DL), %entrapment efficiency (%EE), and particle size were selected as dependent variables. The developed RIF-SLNs were characterized for particle size, polydispersity index, zeta potential, %EE, %DL, differential scanning calorimetry, X-ray diffraction, and TEM analysis. The mean diameter of RIF-SLNs was found to be 456 ± 11 nm, %EE of 84.12 ± 2.78%, and %DL of 15.68 ± 1.52%. The in vitro lipolysis experiments revealed that RIF-SLNs stabilized using poloxamer 188, exhibited antilipolytic effect. Furthermore, the in vitro GI stability studies (at pH 1.2, pH 4.5, pH 6.8, and pH 7.4) revealed that the developed system could withstand various gastrointestinal tract media. The in vitro dissolution studies depicted biphasic drug release profile for drug-loaded SLNs revealing best fit with Weibull model. The accelerated stability studies for 6 months does not revealed any significant change in characteristics of developed RIF-SLNs.
Subject(s)
Antitubercular Agents/administration & dosage , Drug Carriers/chemistry , Nanoparticles/chemistry , Rifampin/administration & dosage , Tuberculosis/drug therapy , Antitubercular Agents/chemistry , Biological Availability , Chemistry, Pharmaceutical , Drug Compounding , Drug Liberation , Drug Stability , Humans , Lipids/chemistry , Particle Size , Rifampin/chemistry , X-Ray DiffractionABSTRACT
The major challenge for the treatment of inflammatory bowel disease (IBD) is the incompetence to deliver the drug molecule selectively at the site of inflammation. Taking this into consideration, we proposed development of mannosylated nanostructured lipid carrier system (Mn-NLCs) for active targeting and site-specific delivery of budesonide to the inflamed tissues. The developed Mn-NLCs were characterized for particle size and size distribution, zeta potential, %entrapment efficiency, FTIR and TEM analysis. Furthermore, to ensure delivery of developed cargo to the colonic region, the Mn-NLCs were encapsulated using Eudragit® S100 coated pellets. The in vivo evaluation of developed system was performed by employing oxazolone colitis rat model. The average particle size of Mn-NLCs (301.7 ± 2.88 nm) was found to be more than that of unconjugated NLCs (284.0 ± 4.53 nm) with marginally reduced % entrapment efficiency (90.88 ± 3.86%). The in vitro cytotoxicity studies using J774A.1 cell line revealed that Mn-NLCs were non-toxic as compared to pure drug. The in vivo evaluation depicted that Mn-NLCs showed significant reduction in clinical activity scoring, macroscopic and microscopic indexing, colonic myeloperoxidase activity and inflammatory cytokines. In conclusion, the developed Mn-NLCs appear to be promising for the treatment of IBD by selectively targeting inflamed colonic region as compared to unconjugated nanoparticulate system.
Subject(s)
Drug Carriers/chemistry , Engineering , Inflammatory Bowel Diseases/drug therapy , Lipids/chemistry , Nanoparticles/chemistry , Body Weight/drug effects , Budesonide/chemistry , Budesonide/pharmacology , Budesonide/therapeutic use , Cell Line , Cell Survival/drug effects , Colon/drug effects , Colon/pathology , Drug Carriers/pharmacology , Drug Liberation , Humans , Inflammatory Bowel Diseases/pathology , Kinetics , Lipids/pharmacology , Mannose/chemistry , Organ Size/drug effects , Surface PropertiesABSTRACT
The major challenge involved in the treatment of inflammatory bowel disease is targeted delivery of the drug at the site of inflammation. As nanoparticles possess the ability to accumulate at the site of inflammation, present investigation aims at development of Budesonide-loaded nanostructured lipid carrier systems (BDS-NLCs) for the treatment of inflammatory bowel disease. BDS-NLCs were prepared by employing a high pressure homogenization technique. Various preliminary trials were performed for optimization of the NLCs in which different processes, as well as formulation parameters, were studied. The BDS-NLCs was optimized statistically by applying a 3-factor/3-level Box-Behnken design. Drug concentration, surfactant concentration, and emulsifier concentration were selected as independent variables, and % entrapment efficiency and particle size were selected as dependent variables. The best batch comprises of 10%, 7%, and 20% w/w concentration of drug, surfactant, and emulsifier, respectively, with % entrapment efficiency of 92.66 ± 3.42% and particle size of 284.0 ± 4.53 nm. Further, in order to achieve effective delivery of nanoparticulate system to colonic region, the developed BDS-NLCs were encapsulated in Eudragit® S100-coated pellets. The drug release studies of pellets depict intactness of BDS-NLCs during palletization process, with f2 value of 75.879. The in vitro evaluation of enteric-coated pellets revealed that a coating level of 15% weight gain is needed in order to impart lag time of 5 h (transit time to reach colon). The results of the study demonstrate that the developed BDS-NLCs could be used as a promising tool for the treatment of inflammatory bowel disease.