Encapsulation of Polyphenols from Lycium barbarum Leaves into Liposomes as a Strategy to Improve Their Delivery

This study is focused on the encapsulation of polyphenols from Lycium barbarum leaves into liposomes as a strategy to improve their delivery. Liposomes loaded with Lycium barbarum leaves extract were obtained and characterized for particle size, polydispersity, entrapment efficiency, and stability. Liposomes presented entrapment efficiency higher than 75%, nanometric particle size, narrow polydispersity, and good stability over three months at 4 °C. The liposomes containing Lycium barbarum offered a slower release of polyphenols with attenuated burst effect compared with the dissolution of free Lycium barbarum extract in phosphate buffer solution at pH 7.4. Moreover, an in vitro pretreatment of 24 h with loaded liposomes showed a cytoprotective effect against H2O2-induced cytotoxicity on L-929 mouse fibroblasts cells. These preliminary findings imply that liposomes could be successfully employed as carriers for polyphenols in pharmaceutical applications.

Model load in case of an internal explosion

Introduction. Presently, there are no model loads that describe the burst effect of an internal explosion. The goal of the article is to design a model load that characterizes an internal explosion with regard for the effect of inertial safety structures. The author provides relevant examples.Methods. The experiment and the numerical modeling identify the characteristics of an internal explosion, primarily, its destructive effect. First of all, these characteristics include the pressure value and rate in the process of the first peak formation. A drop follows the first peak. Another rise to the second peak is followed by the final pressure drop. The rise to the first peak is described by a cubic parabola. The constant value of pressure is equal to the highest value of the two peaks. It replaces the drop and rise between the peaks. The linear dependence describes the area of the final pressure drop, so that the deformation is completed at the end point. The time of the pressure rise is determined by breakup, and it takes account of the characteristics of safety structures. The time of the second peak is the time when the flame area is maximal.Results and discussion. The deformation that may occur before the first peak represents a solution to the equation, describing the beam motion. This equation is provided in the article. The deformation between the peaks is determined by the balance of energy. The deformation, that occurs when the pressure drops, is identified by the solution to the motion equation. The solution is subject to the deformation completion condition.Conclusions. The results show that the time between the peaks is important when the pressure is close to maximal. The analysis identifies the conditions under which deformation remains elastic. These results can be contributed to the assessment of the bearing capacity of buildings that accommodate explosive production facilities. This approach ensures conservative results.

Pharmacokinetic Appraisal of Carprofen Delivery from Intra-Articular Nanoparticles: A Population Modeling Approach in Rabbits

Osteoarthritis is frequently treated in veterinary settings with non-steroidal anti-inflammatory drugs (NSAID) such as carprofen (CP). Its action over the articular cartilage can be enhanced by increasing drug uptake into the cartilage, alongside its site of action, and anticipating its rapid distribution towards the bloodstream. A pharmacokinetic study to evaluate carprofen nanoparticles (NP) after intraarticular administration (IA) in rabbits was performed through a modeling allometric approach. The pharmacokinetic analysis of plasma profiles showed a rapid CP distribution outwards the synovial chamber but mainly remaining in plasma (Vc = 0.14 L/5 Kg), according to its high protein-binding. The absorption data modeling showed the occurrence of two different release–absorption rate processes after nanoparticle administration in the synovial space, i.e., a fast rate process causing a burst effect and involving the 59.5% of the total CP absorbed amount and a slow rate process, involving 40.5%. Interestingly, the CP burst effect inside the joint space enhances its diffusion towards cartilage resulting in CP accumulation in about three times higher concentrations than in plasma. In line with these results, the normalized-by-dose area under the concentration vs. time curve (AUC) values after IA were 80% lower than those observed after the intravenous. Moreover, the slower slope of the concentration–time terminal phase after IA administration vs. intravenous (IV) suggested a flip-flop phenomenon (0.35 h-1 vs. 0.19 h-1). Notably, CP clearances are predictive of the pharmacokinetic (PK) profile of CP in healthy humans (0.14 L/h/5 kg vs. 2.92 L/h/70 kg) although an over-estimation has been detected for cats or dogs (10 times and 4 times, respectively). This fact could probably be attributed to inter-species metabolic differences. In summary, despite the limited number of animals used, this study shows that the rabbit model could be suitable for a predictive evaluation of the release enhancement of CP-NP towards the biophase in arthritic diseases not due to sterical retention of the formulation.

The Correlation between Physical Crosslinking and Water-Soluble Drug Release from Chitosan-Based Microparticles

Microparticles containing water-soluble zidovudine were prepared by spray-drying using chitosan glutamate and beta-glycerophosphate as an ion crosslinker (CF). The Box–Behnken design was applied to optimize the microparticles in terms of their drug loading and release behavior. Physicochemical studies were undertaken to support the results from dissolution tests and to evaluate the impact of the crosslinking ratio on the microparticles’ characteristics. The zidovudine dissolution behavior had a complex nature which comprised two phases: an initial burst effect followed with a prolonged release stage. The initial drug release, which can be modulated by the crosslinking degree, was primarily governed by the dissolution of the drug crystals located on the microparticles’ surfaces. In turn, the further dissolution stage was related to the drug diffusion from the swollen polymer matrix and was found to correlate with the drug loading. Differential Scanning Calorimetry (DSC) studies revealed the partial incorporation of a non-crystallized drug within the polymer matrix, which correlated with the amount of CF. Although CF influenced the swelling capacity of chitosan glutamate microparticles, surprisingly a higher amount of CF did not impact the time required for 80% of the drug to be released markedly. The formulation with the lowest polymer:CF ratio, 3:1, was selected as optimal, providing satisfactory drug loading and displaying a moderate burst effect within the first 30 min of the study, followed with a prolonged drug release of up to 210 min.

Magnetite mesoporous silica nanoparticles embedded in carboxybetaine methacrylate for application in hyperthermia and drug delivery

Magnetite mesoporous silica nanoparticles (MMSNs) are biocompatible and can easily deliver a drug to the target tissue, but there are two challenges: burst effect and protein corona.

Design and Evaluation of a Delivery System Based on Liposomes for Armoracia rusticana Extract

The aim of this paper was the design and evaluation of delivery system for Armoracia rusticana leaves extract with the purpose to use such systems in food or cosmetic field. Liposomes loaded with Armoracia rusticana were prepared by film hydration method and presented good entrapment efficiency, nano-sizes ([150 nm), low polydispersity index and good stability over 90 days at 4oC. In vitro drug release study showed the ability of liposomes to provide slow release of extract with reduced burst effect compared to free extract. These promising results suggest that liposomes could be exploited as carriers for herbal ingredients.

Highly Soluble Drugs Directly Granulated by Water Dispersions of Insoluble Eudragit® Polymers as a Part of Hypromellose K100M Matrix Systems

The aim of the present study was to investigate the suitability of insoluble Eudragit® water dispersions (NE, NM, RL, and RS) for direct high-shear granulation of very soluble levetiracetam in order to decrease its burst effect from HPMC K100M matrices. The process characteristics, ss-NMR analysis, in vitro dissolution behavior, drug release mechanism and kinetics, texture profile analysis of the gel layer, and PCA analysis were explored. An application of water dispersions directly on levetiracetam was feasible only in a multistep process. All prepared formulations exhibited a 12-hour sustained release profile characterized by a reduced burst effect in a concentration-dependent manner. No effect on swelling extent of HPMC K100M was observed in the presence of Eudragit®. Contrary, higher rigidity of formed gel layer was observed using combination of HPMC and Eudragit®. Not only the type and concentration of Eudragit®, but also the presence of the surfactant in water dispersions played a key role in the dissolution characteristics. The dissolution profile close to zero-order kinetic was achieved from the sample containing levetiracetam directly granulated by the water dispersion of Eudragit® NE (5% of solid polymer per tablet) with a relatively high amount of surfactant nonoxynol 100 (1.5%). The initial burst release of drug was reduced to 8.04% in 30 min (a 64.2% decrease) while the total amount of the released drug was retained (97.02%).