Lipid nano-carriers loaded with Cannabis sativa extract for epilepsy treatment - in vitro characterization and in vivo efficacy studies.

Taking into consideration the latest reported beneficial anticolvusant effects of cannabidiol (CBD) and cannabiodiolic acid (CBDA) for clinical applications and the advantages of lipid nano-systems as carriers for targeted brain delivery, the aim of this study was set in direction of in vitro physico-chemical and biopharmaceutical characterization and in vivo evaluation of nanoliposomes and nanostructured lipid carriers loaded with Cannabis sativa extract intended for safe and efficient transport via blood-brain barrier and treatment of epilepsy. These nanoliposomes and nanostructured lipid formulations were characterized with z-average diameter <200 nm, following unimodal particle size distribution, negative values for Z-potential, high drug encapsulation efficiency and prolonged release during 24h (38.84-60.91 %). Prepared formulations showed statistically significant higher antioxidant capacity compared to the extract. The results from in vivo studies of the anticonvulsant activity demonstrated that all formulations significantly elevated the latencies for myoclonic, clonic and tonic seizures and, therefore, could be used in preventing different types of seizures. A distinction in the potential of the nano-systems was noted, which was probably anticipated by the type and the characteristics of the prepared formulations.

Design and evaluation of nanostructured lipid carriers loaded with Salvia officinalis extract for Alzheimer's disease treatment.

Considering the potential of Salvia officinalis in prevention and treatment of Alzheimer's disease (AD), as well as the ability of nanostructured lipid carriers (NLC) to successfully deliver drug molecules across blood-brain barrier (BBB), the objective of this study was design, development, optimization and characterization of freeze-dried salvia officinalis extract (FSE) loaded NLC intended for intranasal administration. NLC were prepared by solvent evaporation method and the optimization was carried out using central composite design (CCD) of experiments. Further, the optimized formulation (NLCo) was coated either with chitosan (NLCc) or poloxamer (NLCp). Surface characterization of the particles demonstrated a spherical shape with smooth exterior. Particle size of optimal formulations after 0.45 µm pore size filtration ranged from 127 ± 0.68 nm to 140 ± 0.74 nm. The zeta potential was -25.6 ± 0.404 mV; 22.4 ± 1.106 mV and - 6.74 ± 0.609 mV for NLCo, NLCc, and NLCp, respectively. Differential scanning calorimetry (DSC) confirmed the formation of NLC whereas Fourier-transform infrared spectroscopy confirmed the FSE encapsulation into particles. All formulations showcased relatively high drug loading (>86.74 mcg FSE/mg solid lipid) and were characterized by prolonged and controlled release that followed Peppas-Sahlin in vitro release kinetic model. Protein adsorption studies revealed the lowest adsorption of the proteins onto NLCp (43.53 ± 0.07%) and highest protein adsorption onto NLCc (55.97 ± 0.75%) surface. The modified ORAC assay demonstrated higher antioxidative activity for NLCo (95.31 ± 1.86%) and NLCc (97.76 ± 4.00%) as compared to FSE (90.30 ± 1.53%). Results obtained from cell cultures tests pointed to the potential of prepared NLCs for FSE brain targeting and controlled release.

5-Fluorouracil in topical liposome gels for anticancer treatment--formulation and evaluation.

Liposome gels bearing an antineoplastic agent, 5-fluorouracil, intended for topical application have been prepared and drug release properties in vitro have been evaluated. Different formulations of liposomes were prepared by the film hydration method by varying the lipid phase composition (PL 90H/cholesterol mass ratio) and hydration conditions of dry lipid film (drug/aqueous phase mass ratio). Topical liposome gels were prepared by incorporation of lyophilized liposomes into a structured vehicle (1%, m/m, chitosan gel base). Also, hydrogels containing different concentrations of 5-fluorouracil were prepared and drug release properties were investigated. The rate of drug release from liposome gels was found to be dependent on the bilayer composition and the dry lipid film hydration conditions. Also, liposomes embedded into a structured vehicle of chitosan showed significantly slower release than hydrogels. The drug release obeyed the Higuchi diffusion model, while liposomes acted as reservoir systems for continuous delivery of the encapsulated drug.