Chitosan-coated Nanoliposomes Research Articles

Chitosan-coated nanoliposome: An approach for simultaneous encapsulation of caffeine and roselle-anthocyanin in beverages

The objective of the present research was to develop chitosan-coated nanoliposomes using a modified heating method as a delivery system for simultaneous encapsulation of caffeine and roselle anthocyanin to fortify beverage. Response surface methodology was used to ascertain the optimized formulation, aiming to maximize the encapsulation efficiency, minimize the particle size, and maximize the zeta potential. The liposomes fabricated under the optimized conditions (lecithin to cholesterol ratio of 13 and wall to core ratio of 2.16) showed encapsulation efficiency values of 66.73 % for caffeine and 97.03 % for anthocyanin, with a size of 268.1 nm and a zeta potential of −39.11 mV. Fourier transform infrared spectroscopy confirmed the formation of hydrogen bonds between the polar sites of lecithin and the loaded core compounds. Thermal analysis suggested the successful encapsulation of the caffeine and anthocyanin. Transmission and scanning electron microscopy images confirmed a uniform spherical shape with a smooth surface. Fortifying the model beverage with the liposome and the chitosan-coated nanoliposome revealed higher values of encapsulation efficiency of anthocyanin (70.33 ± 3.11 %), caffeine (86.37 ± 2.17 %) and smaller size (280.5 ± 0.74 nm) of the chitosan-coated nanoliposomes at the end of 60the days. A hedonic sensory test of the fortified beverage with chitosan-coated nanoliposomes confirmed an improvement in the organoleptic properties of the beverage by masking its bitterness (receiving three more sensory scores in perceiving the bitterness intensity). Overall, our study indicates that the high potential of the chitosan-coated nanoliposomes for the simultaneous loading of the caffeine and anthocyanin, as well as their possible application in food and beverage formulations.

Chitosan-Coated Nanoliposomes: Exploring the Impact on Physicochemical Properties, Stability, Antioxidant Activity, and Molecular Characterization of Chlorella-Peptide Fractions

Chitosan-Coated Nanoliposomes: Exploring the Impact on Physicochemical Properties, Stability, Antioxidant Activity, and Molecular Characterization of Chlorella-Peptide Fractions

Novel Chitosan-Coated Liposomes Coloaded with Exemestane and Genistein for an Effective Breast Cancer Therapy.

For achieving high effectiveness in the management of breast cancer, coadministration of drugs has attracted a lot of interest as a mode of therapy when compared to a single chemotherapeutic agent that often results in reduced therapeutic end results. Owing to their proven effectiveness, good patient compliance, and lower costs, oral anticancer drugs have received much attention. In the present work, we formulated the chitosan-coated nanoliposomes loaded with two lipophilic agents, namely, exemestane (EXE) and genistein (GEN). The formulation was prepared using the ethanol injection method, which is considered a simple method for getting the nanoliposomes. The formulation was optimized using Box-Behnken design (BBD) and was extensively characterized for particle size, ζ-potential, Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. The sizes of conventional and coated liposomes were found to be 104.6 ± 3.8 and 120.3 ± 6.4 nm with a low polydispersity index of 0.399 and 0.381, respectively. The ζ-potential of the liposomes was observed to be -16.56 mV, which changed to a positive value of +22.4 mV, clearly indicating the complete coating of the nanoliposomes by the chitosan. The average encapsulation efficiency was found to be between 70 and 80% for all prepared formulations. The compatibility of the drug with excipients and complete dispersion of the drug inside the system were verified by FTIR, XRD, and DSC studies. Furthermore, the in vitro release studies concluded the sustained release pattern following the Korsmeyer-Peppas model as the best-fitting model with Fickian diffusion. Ex vivo studies showed better permeation of the chitosan-coated liposomes, which was further confirmed by confocal studies. The prepared chitosan-coated liposomes showed superior antioxidant activity (94.56%) and enhanced % cytotoxicity (IC50 7.253 ± 0.34 μM) compared to the uncoated liposomes. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay displayed better cytotoxicity of the chitosan-coated nanoliposomes compared to the plain drug, showing the better penetration and enhanced bioavailability of drugs inside the cells. The formulation was found to be safe for administration, which was confirmed using the toxicity studies performed on an animal model. The above data suggested that poorly soluble lipophilic drugs could be successfully delivered via chitosan-coated liposomes for their effective delivery in breast cancer.

Effect of temperature and shear stress on properties of nanovesicles carrying hydrolyzed pollen protein

In this study, the effect of storage (65 °C, 24 h) and shear rates (2-100 s−1, 10 min) on the particle size, poly-dispersity index (PDI), encapsulation efficiency (EE), Angiotensin-converting enzyme (ACE) and DPPH radical inhibition, iron ion reduction ability and flow behavior of nanovesicles containing hydrolyzed bee pollen (produced by alcalase and pepsin) were evaluated. Nanoliposomes were coated by chitosan (0.2 % w/w). After storage at 65 °C, the size of the nanovesicles raised 2–2.5 folds while EE showed 5–8 % decline. ACE and DPPH radical inhibition activity were also decreased. After applying the shear stress, PDI was increased significantly (P<0.05), while EE of the nanoniosomes showed a drastic decline (P<0.05). Nanoliposomes and nanoniosomes exhibited decline in the ACE inhibitory and antioxidant activity. At low shear rates Newtonian-like and weak pseudo-plastic behavior of the chitosan-coated nanoliposomes were observed. The flow index (n), (k) and (R2) indicated the suitability of power law model for describing the flow characteristics.

Encapsulation of caffeine in chitosan-coated nanoliposomes and its application in drink formulation

In this study, chitosan-coated nanoliposomes in ratios of 9:1, 8:2, 7:3 and 6:4 lecithin-cholesterol were created via the thin-film hydration method, as a practical vehicle for encapsulation of caffeine. Then, the effect of lecithin -cholesterol concentrations on particle size, particle size distribution, zeta potential and encapsulation efficiency (EE) were evaluated. FTIR was performed to investigate possible reactions between caffeine and nano-chitosomes wall materials. Subsequently, the morphology of nano-chitosome with 9:1 ratio of lecithin-cholesterol loaded with caffeine, was shown by Field emission scanning electron microscopy (FE-SEM). Nano-chitosomes with a ratio of 9:1 lecithin-cholesterol were used in the formulation of drinks. The sensory properties, as well as physical and chemical characteristics such as acidity, pH, and Brix degree, were evaluated for the prepared drinks. Average particle size and particle size distribution for different lecithin-cholesterol ratios were in the range of 135.5–533.5 nm and 0.31–0.41, respectively. Zeta potential values were also obtained in the range of +40.96 to +50.5. The values of encapsulation efficiency for different lecithin -cholesterol ratios were measured in the range of 70.71–91.20%. The results of FTIR confirmed the successful loading of caffeine in nano-chitosomes. The sensory evaluation of the beverages indicated that the taste of the samples contained caffeine nano-chitosome was more acceptable than those that contained free caffeine. The findings of this study demonstrate that nano-chitosome is an effective system for masking the bitter taste of caffeine.

Chitosan‐coated nanoliposomes for the enhanced stability of walnut angiotensin‐converting enzyme (ACE) inhibitory peptide

This study encapsulated walnut angiotensin-converting enzyme (ACE) inhibitory peptides within nanoliposomes and then modified them with chitosan. The resulting effect of the nanoliposome loading and chitosan coating on physicochemical characteristics, stability, bioactivity, chemical structure, and morphology of the encapsulated peptides was assessed. The resulting particle size and polymer dispersity index revealed that the chitosan-coated nanoliposomes loaded with walnut ACE inhibitory peptides (WAIP) (CL-P) exhibited higher physical stability compared with the nanoliposomes loaded with WAIP (L-P). The encapsulation efficiency (EE) of CL-P increased from 73.32% to 76.13% after chitosan modification, and the EE of L-P and CL-P could be maintained by storage at 4°C. In addition, the antioxidant activity and ACE inhibitory activity of the peptides were effectively protected by L-P and CL-P during storage. Fourier transform infrared spectroscopy showed that the nanoliposomes were bound in ionic form with both the peptides and chitosan. Transmission electron micrographs indicated the presence of vesicle-like carriers with a reservoir-type structure. This study highlights the potential of nanoliposomes and their modification with chitosan to increase the stability and bioactivity retention of ACE inhibitory peptides. PRACTICAL APPLICATION: Chitosan-coated nanoliposomes loaded with walnut ACE inhibitory peptides were prepared in this study. Chitosan coating increased nanoliposomes' encapsulation efficiency and provided higher physical stability. In addition, the bioactivity of the walnut ACE peptides was effectively protected during storage. This study was relevant for improving the storage and transportation used for nanoliposome systems applied in the food and health product industry.

Design of experiment based formulation optimization of chitosan-coated nano-liposomes of progesterone for effective oral delivery

Design of experiment based formulation optimization of chitosan-coated nano-liposomes of progesterone for effective oral delivery

Liposome System for Encapsulation of Spirulina platensis Protein Hydrolysates: Controlled-Release in Simulated Gastrointestinal Conditions, Structural and Functional Properties

This study aimed to evaluate the physicochemical, structural, antioxidant and antibacterial properties of chitosan-coated (0.5 and 1% CH) nanoliposomes containing hydrolyzed protein of Spirulina platensis and its stability in simulated gastric and intestine fluids. The chitosan coating of nanoliposomes containing Spirulina platensis hydrolyzed proteins increased their size and zeta potential. The fourier transform infrared spectroscopy (FT-IR) test showed an effective interaction between the hydrolyzed protein, the nanoliposome, and the chitosan coating. Increasing the concentration of hydrolyzed protein and the percentage of chitosan coating neutralized the decreasing effect of microencapsulation on the antioxidant activity of peptides. Chitosan coating (1%) resulted in improved stability of size, zeta potential, and poly dispersity index (PDI) of nanoliposomes, and lowered the release of the hydrolyzed Spirulina platensis protein from nanoliposomes. Increasing the percentage of chitosan coating neutralized the decrease in antibacterial properties of nanoliposomes containing hydrolyzed proteins. This study showed that 1% chitosan-coated nanoliposomes can protect Spirulina platensis hydrolyzed proteins and maintain their antioxidant and antibacterial activities.

Chitosan-coated nanoliposomes for efficient delivery of betanin with enhanced stability and bioavailability

Betanin is a high-value health-promoting food ingredient. However, the bioavailability of betanin is constrained by its low stability. In this study, for the first time, betanin was stabilized and delivered using chitosan-coated nanoliposomes (CC-NLs). The CC-NLs were firstly synthesized and characterized. The results showed that increasing chitosan concentration from 0% to 1.0% increased particle size of CC-NLs from 156.4 nm to 217.2 nm. With the use of CC-NLs prepared with 0.6% chitosan, it was found that increasing pH from 1.5 to 9.0 reduced zeta potential of CC-NLs from 8.62 mv to-9.65 mv while the average size of CC-NLs of 221.40 nm peaked at pH 5.5. In aqueous solution, 29.0% of loaded betanin was released from NLs compared to 15.8% from CC-NLs. The in vitro digestion analysis indicated that uncoated NLs and CC-NLs had similar stabilities and relatively stable in oral and gastric fluids. However, in intestinal fluid, the average size of both NLs and CC-NLs were significantly reduced due to bile salt and trypsin. Furthermore, in vitro antioxidant activity assay results showed that betanin delivered by CC-NLs had the highest ORAC and PSC values. This study demonstrated that betanin could be efficiently delivered by CC-NLs with improved stability and bioavailability. The information generated from this study is very useful for the applications of betanin in functional food, pharmaceutical and cosmetics industry. • Betanin was succussfully loaded on chitosan-coated nanoliposomes (CC-NLs). • Controlled release of betanin from CC-NLs was achieved. • CC-NLs were stable in simulated salivary and gastric fluids and were digested in simulated intestinal fluid. • Betanin delivered by CC-NLs had the highest in vitro and cellular antioxidant activities.

Effect of chitosan coating on the properties of nanoliposomes loaded with oyster protein hydrolysates: Stability during spray-drying and freeze-drying

Oyster protein hydrolysate (OPH) has high bioactivity and excellent performance, but its application in food formulation is still limited due to poor flavor and instability. In the present study, OPH was prepared by enzymatic hydrolysis and loaded into nanoliposomes. Then, the effects of chitosan coating (0, 0.25, 0.5, and 1.0%) on the physical properties, stability, and antioxidant activity were evaluated. The results showed that 1% chitosan-coated nanoliposomes had high encapsulation efficiency (EE) and physical stability. Additionally, chitosan coating slowed the release rate of nanoliposomes and increased the retention rate of antioxidant activity of OPH. The stability of the uncoated/coated nanoliposomes in a maltodextrin matrix by spray/freeze drying was evaluated. FTIR spectrum showed that hydrogen bonds, hydrophobic, and electrostatic interactions had been formed between chitosan-coated nanoliposomes and maltodextrin. Chitosan coating significantly improved the physical stability and antioxidant activity retention of nanoliposomes during powder reconstitution.

Application of Nanoliposomes Containing Nisin and Crocin in Milk.

Purpose: This study aimed to investigate the effects of nanoliposomes containing crocin and nisin in milk samples as a food model. Therefore, three formulations were prepared and compared, including (1) milk samples containing free nisin and crocin, (2) samples with nanoliposomes containing nisin and crocin, and (3) nisin and crocin-loaded nanoliposomes coated with chitosan. Methods: In order to find the optimum amount of both bioactives within nanoliposomes, analyses of size, polydispersity index (PDI), zeta potential, and encapsulation efficiency were accomplished. Then, the best formulated nanoliposome was evaluated and compared with a solution containing free bioactives and nanoliposomes coated with chitosan using other experiments, including antioxidant and antibacterial activities, viscosity, colorimetric and bacterial growth. Results: The best nanoliposomal system based on the factors of size, PDI, zeta potential, and encapsulation efficiency was related for the nanocarrier with 4 mg crocin, 4.5 mg nisin, and 40 mg lecithin. Based on the results obtained, both nanoliposome (a*=5.41) and chitosancoated nanoliposome (a*=5.09) solutions could significantly (P<0.05) reduce the redness of milk induced by free bioactives (a*=12.32). However, viscosity of milk in chitosan-coated nanoliposome solution was found to be higher (3.42 cP) than other formulations (viscosity of samples with free bioactives was 1.65 cP and viscosity of samples containing nanoliposome was 1.71 cP). In addition, chitosan-coated nanoliposomes could inhibit the growth of Listeria monocytogenes stronger than other samples. Conclusion: Encapsulation of nisin and crocin in nanoliposomes showed promising results for preserving food safety and quality.

Formulation of chitosan coated nanoliposomes for the oral delivery of colistin sulfate: in vitro characterization, 99mTc-radiolabeling and in vivo biodistribution studies

Colistin sulfate is a very important antibiotic for the treatment of multidrug-resistant Gram-negative infections. Unfortunately, it has low oral bioavailability and several side effects following parenteral administration. The present study aims to develop chitosan-coated colistin nanoliposomes to improve the stability in the gastrointestinal tract and to enhance the oral delivery of colistin. The chitosan-coated colistin nanoliposomes were obtained via thin-film evaporation and electrostatic deposition methods using either Span 60, Tween 65 or Tween 80 as surfactants with different cholesterol: surfactant: soya lecithin ratios. The influence of systems variables was further characterized by vesicle size analysis, zeta potential (ZP), poly dispersibility index (PDI), and also their entrapment efficiency percentage (EE %) was evaluated. Various systems were formed with vesicle sizes in the nano-range, 155.64 ± 12.53 nm to 315.64 ± 15.90 nm, and EE % of 45.2 ± 2.9% to 81.8 ± 2.9%. Moreover, the ZP value of the prepared nanoliposomes switched from a negative to a positive value after chitosan coating. To track the released colistin in vivo, technetium 99m (99mTc) was incorporated into the optimum system (S-3) system via direct coupling with colistin. Chitosan-coated 99mTc-colistin nanoliposome, 99mTc-colistin suspension, and 99mTc-chitosan-coated nanoliposomes (placebo) were administered orally into bacterial infection (Escherichia coli) bearing mice. The biodistribution results showed that chitosan-coated nanoliposome significantly enhanced the bioavailability of colistin compared to colistin suspension (the commercially available). Moreover, the system effectively improved the localization of colistin at the infected muscle. In conclusion, this approach offers a promising tool for enhanced oral delivery of colistin.

Preparation, characterization and release behavior of chitosan-coated nanoliposomes (chitosomes) containing olive leaf extract optimized by response surface methodology

The online version contains supplementary material available at (10.1007/s13197-021-04972-2).

Development and characterization of chitosan-coated nanoliposomes for encapsulation of caffeine

In the present study, chitosan-coated nanoliposomes were prepared using thin-film hydration method, as a practical delivery system for encapsulation of caffeine. Response surface methodology (RSM) was applied to determine the optimum conditions for preparation of nanoliposomes based on the encapsulation efficiency, lightness (L*), electrical conductivity and stability. The morphological analysis demonstrated that the developed nanoliposomes were spherical particles with a homogenous distribution and smooth surfaces. The particle size of the samples determined by dynamic light scattering was higher than that observed by field emission scanning electron microscopy (FESEM). The surface charges of nanoliposome and chitosome were −25 and 31.9 mV, respectively, exhibiting a relatively stable nanostructure. Differential scanning calorimetry (DSC) revealed that there existed a broad peak at 226.74 °C. On the basis of the release profile of the developed nanostructured vehicles, most of caffeine released in the small intestine and chitosan-coated nanoliposomes presented a slower release rate compared to the nanoliposomal system. Kopcha model could describe the release behavior of cafeine from fabricated carriers. Overall, the results showed the potential of chitosomes for caffeine retention and sustained release in the digestive system, bearing more advantages compared to nanoliposomes.

Growth-Inhibitory Effect of Chitosan-Coated Liposomes Encapsulating Curcumin on MCF-7 Breast Cancer Cells.

Current anticancer drugs exhibit limited efficacy and initiate severe side effects. As such, identifying bioactive anticancer agents that can surpass these limitations is a necessity. One such agent, curcumin, is a polyphenolic compound derived from turmeric, and has been widely investigated for its potential anti-inflammatory and anticancer effects over the last 40 years. However, the poor bioavailability of curcumin, caused by its low absorption, limits its clinical use. In order to solve this issue, in this study, curcumin was encapsulated in chitosan-coated nanoliposomes derived from three natural lecithin sources. Liposomal formulations were all in the nanometric scale (around 120 nm) and negatively charged (around −40 mV). Among the three lecithins, salmon lecithin presented the highest growth-inhibitory effect on MCF-7 cells (two times lower growth than the control group for 12 µM of curcumin and four times lower for 20 µM of curcumin). The soya and rapeseed lecithins showed a similar growth-inhibitory effect on the tumor cells. Moreover, coating nanoliposomes with chitosan enabled a higher loading efficiency of curcumin (88% for coated liposomes compared to 65% for the non-coated liposomes) and a stronger growth-inhibitory effect on MCF-7 breast cancer cells.

Preparation, Characterization, and Release Kinetics of Chitosan-Coated Nanoliposomes Encapsulating Curcumin in Simulated Environments.

Curcumin, a natural polyphenol, has many biological properties, such as anti-inflammatory, antioxidant, and anti-carcinogenic properties, yet, its sensitivity to light, oxygen, and heat, and its low solubility in water renders its preservation and bioavailability challenging. To increase its bioaccessibility, we fabricated nanoliposomes and chitosan-coated nanoliposomes encapsulating curcumin, and we evaluated the systems in terms of their physicochemical characteristics and release profiles in simulated gastrointestinal mediums. Chitosan-coating enhanced the stability of nanoliposomes and slowed the release of curcumin in the simulated gastrointestinal (GI) environment. This study demonstrates that nanoliposomes and chitosan-coated nanoliposomes are promising carriers for poorly soluble lipophilic compounds with low oral bioavailability, such as curcumin.

Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems

Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity.Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods.The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin.Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing.

Encapsulation of the flavonoid quercetin with chitosan-coated nano-liposomes

A facile electrostatic deposition method was proposed to encapsulate quercetin within chitosan/lecithin polymeric nanocapsules, with the aim to protect quercetin against degradation and enhance its biocompatibility. Quercetin loaded polymeric nanocapsules (Q-NPs) were characterized in terms of size, morphology, encapsulation efficiency, storage stability, anti-oxidant and anti-proliferative activities. The obtained homogeneous and spherical Q-NPs have small particle size and high encapsulation efficiency (71.14%). The storage stability and antioxidant activity was improved compared with native quercetin. MTT assay and trypan blue exclusion assay showed the inhibitory effect of Q-NPs on HepG2 cells were comparable with that of free quercetin. This novel nanocapsule may provide a new system for the protection and delivery of a range of hydrophobic chemicals in vivo and food products.

Biopolymer-coated nanoliposomes as carriers of rainbow trout skin-derived antioxidant peptides

In this study, an antioxidant peptide fraction with a molecular mass<30kDa (PF30) isolated from rainbow trout (Oncorhynchus mykiss) skin gelatin hydrolysates was encapsulated in chitosan-coated nanoliposomes. The mean particle size of liposomal nanovesicles containing PF30 was found to be in the range 163.4–234nm with a low polydispersity index (PDI<0.5); furthermore, the ζ-potential changed from +3.9mV in uncoated liposomes to +45.5mV in biopolymer-coated liposomes. FTIR spectra showed electrostatic interactions as well as hydrogen bonding between phospholipid head groups and amine groups of chitosan. The entrapment efficiency of PF30 (2mg/ml) was found to be highest in nanoliposomes coated with 0.4% (w/v) chitosan. Biopolymer-coated liposomes demonstrated more sustained peptide release behavior in vitro. Moreover, the chitosan-coated nanoliposomes maintained the antioxidant activity of the PF30 and could be considered a potential candidate for efficient delivery of bioactive compounds in nutraceutical and functional foods.

Chitosan-coated nano-liposomes for the oral delivery of berberine hydrochloride.

Berberine hydrochloride (BH) possesses various pharmacological properties including anticancer; unfortunately, it has low oral bioavailability and potential side effects for its parenteral administration. Nanoscale delivery carriers can increase the oral bioavailability of BH. Chitosan has interesting biopharmaceutical properties such as nontoxicity, biocompatibility, biodegradability, and mucoadhesiveness, and the ability to open epithelial tight junctions. This study aims to engineer a chitosan-coated nano-liposomal carrier for the oral delivery of BH. The engineered formulation had a size in the nanoscale range. Chitosan-coated nano-liposomes displayed better stability and slower BH release in the simulated gastrointestinal (GI) environment as compared to the uncoated ones. All values of pharmacokinetic analysis for chitosan-coated nano-liposomes were higher than for uncoated ones. These findings demonstrate that chitosan-coated nano-liposomes are more efficient than uncoated ones for the oral delivery of BH. It can be concluded that the stability and delayed BH release in the simulated GI environment were improved with engineered chitosan-coated nano-liposomes. Moreover, since desirable in vitro and in vivo characteristics were achieved, they are promising release devices for the oral delivery of BH increasing the bioavailability of the drug.