Preparation and In Vitro/In Vivo Evaluation of Gliclazide Loaded Eudragit Nanoparticles as a Sustained Release Carriers

ABSTRACT

The aim of this study was to formulate and optimize gliclazide-loaded Eudragit nanoparticles (Eudragit L100 and Eudragit RS) as a sustained release carrier with enhanced efficacy. Eudragit L 100 nanoparticles (ELNP) were prepared by controlled precipitation method whereas Eudragit RSPO nanoparticles (ERSNP) were prepared by solvent evaporation method. The influence of various formulation factors (stirring speed, drug:polymer ratio, homogenization, and addition of surfactants) on particle size, drug loading, and encapsulation efficiency were investigated. The developed Eudragit nanoparticles (L100 and RS) showed high drug loading and encapsulation efficiencies with nanosize. Mean particle size altered by changing the drug:polymer ratio and stirring speed. Addition of surfactants showed a promise to increase drug loading, encapsulation efficiency, and decreased particle size of ELNP as well as ERSNP. Dissolution study revealed sustained release of gliclazide from Eudragit L100 as well as Eudragit RSPO NP. SEM study revealed spherical morphology of the developed Eudragit (L100 and RS) NP. FT-IR and DSC studies showed no interaction of gliclazide with polymers. Stability studies revealed that the gliclazide-loaded nanoparticles were stable at the end of 6 months. Developed Eudragit NPs revealed a decreased t_min (ELNP), and enhanced bioavailability and sustained activity (ELNP and ERSNP) and hence superior activity as compared to plain gliclazide in streptozotocin induced diabetic rat model and glucose-loaded diabetic rat model. The developed Eudragit (L100 and RSPO) NP could reduce dose frequency, decrease side effects, and improve patient compliance.     

Preparation and in vitro/in vivo evaluation of a ketoprofen orally disintegrating/sustained release tablet

Context: Orally disintegrating tablets (ODTs) with sustained release profiles are a new generation of ODTs called orally disintegrating/sustained release tablets (ODSRTs), which are convenient in use and able to slowly release drugs to maintain effective blood concentrations over a prolonged period of time. Ketoprofen, one of non-steroidal anti-inflammatory drugs, is an ideal model drug for ODSRTs.

Methods: We designed a simple two-step process to develop novel ketoprofen orally disintegrating/sustained release tablets (KODSRTs). Firstly, sustained release ketoprofen fine granules were developed by spray drying the aqueous dispersions composed of Eudragit RS-30D, Starch 1500 and PEG 6000. The optimal parameters of spray drying were 100°C for inlet air temperature and 1.5 mL/min for feed rate. Subsequently, the obtained granules were directly compressed into KODSRTs after mixing with lactose, mannitol and a superdisintegrant, crosslinked polyvinylpyrrolidone (PVPP). The characteristics of KODSRTs, especially their potential for extended drug release, were evaluated.

Results: Results of an in vitro release test demonstrated that KODSRTs could slowly release ketoprofen for 24 h after disintegrating within 30 s. Extended release properties of KODSRTs were decided by the ketoprofen sustained release fine granules in tablets. Besides, the disintegration time of KODSRTs depended on the percentage of PVPP in tablets. In vivo pharmacokinetic studies in beagles also showed that KODSRTs possessed a significantly extended release profile compared with ketoprofen normal capsules.

Conclusion: KODSRTs were successfully prepared using a simple two-step process: spray drying and direct compression.     

A chitosan lactate/poloxamer 407-based matrix containing Eudragit RS microparticles for vaginal delivery of econazole: design and in vitro evaluation

A matrix based on chitosan lactate and poloxamer 407 was evaluated as a delivery system for the vaginal administration of the antifungal drug econazole. The matrix was investigated both containing the pure drug and after introducing microparticles of Eudragit RS 100 containing econazole. Eudragit RS 100 microparticles were prepared using an emulsion-extraction method and dispersed in a solution containing chitosan lactate (2% w/w) and poloxamer 407 (1.7% w/w). The microparticles, obtained with a yield of 64% w/w and an encapsulation efficiency of 42% w/w, had a diameter of less than 2 μm and a drug loading of 13% w/w. The compressed matrices, characterized by DSC, swelling, erosion, release and mucoadhesion studies, had behaviours dependent on the relative amounts of the contained microparticles. The matrix without microparticles (MECN) showed zero-order release kinetics, with a maximum drug-release of 60% w/w, while those containing 50 or 75% w/w microparticles showed a diffusion controlled release up to 8 and 16 h, respectively, and a linear trend after those time intervals, caused by the erosion process, which allowed reaching a drug-release of approximately 100% w/w at 22 h. In in vitro experiments, the matrices were mucoadhesive and active in inhibiting the growth of Candida albicans 796.     

Eudragit coating of chitosan-prednisolone conjugate microspheres and in vitro evaluation of coated microspheres

Chitosan-prednisolone conjugate microspheres (Ch-SP-MS) were prepared, and Eudragit coating was applied in order to efficiently deliver the microspheres and drug to the intestinal disease sites. The Eudragit L100-coated microspheres (Ch-SP-MS/EuL100) were examined for particle characteristics and the release of drug and Ch-SP-MS in different pH media at 37°C. Ch-SP-MS were spherical, with a mean size of 4.5 μm and prednisolone content of 3.3% (w/w). Ch-SP-MS/EuL100 were fairly spherical, with a mean size of 22. 5 μm and drug content of 0.32% (w/w). At pH 1.2, the release extent was less than 5% even at 48 h, and Eudragit coating tended to suppress the release. In contrast, at pH 6.8 and 7.4, Ch-SP-MS/EuL100 tended to show somewhat faster drug release than Ch-SP-MS. Ch-SP-MS/EuL100 displayed a release extent of 23 and 27% at pH 6.8 and 7.4, respectively. Ch-SP-MS aggregated at pH 1.2, but almost kept their initial size and shape at pH 6.8 and 7.4. Ch-SP-MS/EuL100 almost maintained their original shape and size at pH 1.2, and gradually released Ch-SP-MS at pH 6.8 and 7.4 due to dissolution of the Eudragit layer. Eudragit coating is suggested to be useful to efficiently deliver Ch-SP-MS to the intestinal disease sites.     

Comparison of simple Eudragit microparticles loaded with prednisolone and Eudragit-coated chitosan-succinyl-prednisolone conjugate microparticles: Part I. Particle characteristics and in vitro evaluation as a colonic delivery system

Objective: Simple Eudragit microparticles loaded with prednisolone and chitosan-succinyl-prednisolone conjugate microparticles coated with Eudragit were prepared and characterized in vitro in order to obtain their basic features as a colonic delivery system.

Materials and methods: Both types of microparticles were prepared by the emulsification-solvent evaporation modified somewhat from the previous one. Their particle size, shape and their drug content were investigated, and in vitro release profiles were examined using JP-15 1st fluid (pH 1.2), JP-15 2nd fluid (pH 6.8) and PBS (pH 7.4) as release media. Furthermore, the regeneration of conjugate microparticles from Eudragit-coated microparticles was investigated under the same incubation conditions.

Results: Simple Eudragit S100 (EuS) microparticles (ES-M) were almost spherical, ca. 1.2 μm diameter, and PD content ca. 3.7% (w/w). Conjugate microparticles (CS-M1) and EuS-coated conjugate microparticles (CS-M1/S) had particle sizes of ca. 2.8 and 15.3 μm, respectively, and PD contents of 5.4 and 2.1% (w/w), respectively. ES-M exhibited suppressed release at pH 1.2, gradual release at pH 6.8 and rapid release at pH 7.4. CS-M1 showed no release at pH 1.2, and very slow release at pH 6.8 and 7.4. CS-M1 regenerated poorly from CS-M1/S at pH 6.8.

Conclusions: Simple Eudragit micrparticles and Eudragit-caoted conjugate microparticles, prepared by the present methods, were found in vitro to be possibly useful as the delivery systems of PD to the lower intestine, although there were differences in their release rate and morphological features.     

Tableting of Eudragit RS and propranolol hydrochloride solid dispersion: effect of particle size, compaction force, and plasticizer addition on drug release

The application of a solid dispersion (SD) system of propranolol HCl and Eudragit RS was evaluated in the preparation of prolonged release tablets. The effects of SD size fraction, compaction force, and inclusion of plasticizers [namely diethylphtalate (DEP) and triethylcitrate (TEC)] on crushing strengths of matrices and release profile of drug were also investigated. The results showed that when compressed as a tablet, the SD system was more efficient in prolonging drug release than physical mixture. This effect was due to formation of much harder tablets of the SD system (crushing strength 8.5 kg) compared with those of physical mixtures (crushing strength 2.7 kg). All matrices of the SD system showed release rate patterns that were best described by the Higuchi equation. It was also shown that the rate of drug release decreased from 19.8% to 9.13% min^- 1/2 as the SD size fraction decreased from 300-350 to 125-250 µm. However, further reduction of size fraction did not significantly affect tablet crushing strength and drug release rate. Increase in compaction force from 5 to 30 kN increased the crushing strength of matrices from 2.9 to 13.6 kg. However, the rate of drug release remained nearly unchanged beyond compaction pressure of 10 kN, indicating that crushing strength of matrices in the range of 8.5-13.6 kg did not affect drug release rate. The addition of 5% or 10% of either plasticizer (DEP or TEC) led to an increase in crushing strength of matrices and more retardation of drug release. This effect was more pronounced for higher concentrations of plasticizers. This effect was probably due to more plastic deformation of matrices under the compaction force, which helped matrices to retain their shape throughout the dissolution test.     

Preparation of DHAQ-loaded mPEG-PLGA-mPEG nanoparticles and evaluation of drug release behaviors in vitro/in vivo

This study describes the preparation and the evaluation of biodegradation monomethoxy (polyethylene glycol)-poly (lactide-co-glycolide)-monomethoxy (polyethyleneglycol) (mPEG-PLGA-mPEG, PELGE) nanoparticles (PELGE-NP) containing mitoxantrone (DHAQ) as a model drug. PELGE copolymers with various molar ratios of lactic to glycolic acid and different molecular weights and various content mPEG were synthesized by ring-opening polymerization. mPEG with weight-average molecular weight (Mw) 2000 or 5000 was introduced as a hydrophilic segment into a hydrophobic PLGA. A double emulsion method with dextran70 as stabilizer in the external aqueous phase was used to prepare the nanoparticles. The drug entrapment efficiencies were more than 80% and the mean diameters of the nanoparticles were less than 200 nm. Various PELGE was studied as biodegradable drug carriers and there in vitro/in vivo release profiles were examined. It was found that drug loading, polymer molecular weight, copolymer composition and end group modifications were critical factors affecting the in vitro/in vivo release properties. The amount of drug released increased as the mPEG contents increased and the molar ratios of lactic acid decreased in vitro. The intravenous (i.v.) administration of mPEG-PLGA–mPEG nanoparticles of DHAQ in mice resulted in prolonged DHAQ residence in systemic blood circulation compared to the intravenous administration of PLGA nanoparticles.     

Directly compressed mini matrix tablets containing ibuprofen: preparation and evaluation of sustained release

Directly compressed mini tablets were produced containing either hydroxypropylmethylcellulose (HPMC) or ethylcellulose (EC) as release controlling agent. The dynamics of water uptake and erosion degree of polymer were investigated. By changing the polymer concentration, the ibuprofen release was modified. In identical quantities, EC produced a greater sustaining release effect than HPMC. Different grades of viscosity of HPMC did not modify ibuprofen release. For EC formulations, the contribution of diffusion was predominant in the ibuprofen release process. For HPMC preparations, the drug release approached zero-order during a period of 8 h. For comparative purposes, tablets with 10 mm diameter were produced.     

Anti-tumor activity of paclitaxel-loaded chitosan nanoparticles: An in vitro study

Chitosan nanoparticles containing the anticancer drug paclitaxel were prepared by a solvent evaporation and emulsification crosslinking method. The physicochemical properties of the nanoparticles were characterized by various techniques, and uniform nanoparticles with an average particle size of 116 ± 15 nm with high encapsulation efficiencies (EE) were obtained. Additionally, a sustained release of paclitaxel from paclitaxel-loaded chitosan nanoparticles was successful. Using different ratios of paclitaxel-to-chitosan, the EE ranged from 32.2 ± 8.21% to 94.0 ± 16.73 %. The drug release rates of paclitaxel from the nanoparticles were approximately, 26.55 ± 2.11% and 93.44 ± 10.96% after 1 day and 13 days, respectively, suggesting the potential of the chitosan nanoparticles as a sustained drug delivery system. Cytotoxicity tests showed that the paclitaxel-loaded chitosan had higher cell toxicity than the individual paclitaxel and confocal microscopy analysis confirmed excellent cellular uptake efficiency. TEM images showed the ultrastructure changes of A2780 cells incubated with paclitaxel-loaded nanoparticles. Flow cytometric analysis revealed two subdiploid peaks for the cells in the paclitaxel-loaded nanoparticles and paclitaxel treated groups, respectively, with the intensity of the former higher than that of the latter. Moreover, the cell cycle was arrested in the G₂-M phase, which was consistent with the action mechanism of the direct administration of paclitaxel. These results indicate that chitosan nanoparticles have potential uses as anticancer drug carriers and also have an enhanced anticancer effect.     

不同载体系统黄连素纤维膜的制备及体外释放行为

利用静电纺丝技术制备了质量分数为10%的黄连素/聚乙烯醇(PVA)和黄连素/聚乙烯吡咯烷酮(PVP)超细纤维,通过红外光谱及扫描电镜照片进行了结构和性能的表征,紫外-可见光分光度计测试了载药超细纤维在人工肠液和人工胃液的体外释药行为。PVP载药纤维膜的累计释药率明显高于PVA载药纤维膜。PVA载药纤维具有较好的缓释效果,有一定的靶向药位;PVP超细纤维膜能够将难溶药物黄连素速溶于体液中,达到提高难溶药物生物利用度的目的。     

Development and in vitro/in vivo evaluation of HPMC/chitosan gel containing simvastatin loaded self-assembled nanomicelles as a potent wound healing agent

The aim of this study was to develop hydroxypropyl methyl cellulose (HPMC)/chitosan gel containing polymeric micelles loaded with simvastatin (Sim) and evaluates its wound healing properties in rats. An irregular full factorial design was employed to evaluate the effects of various formulation variables including polymer/drug ratio, hydration temperature, hydration time, and organic solvent type on the physicochemical characteristics of pluronic F127-cholesterol nanomicelles prepared using the film hydration method. Among single studied factors, solvent type had the most impact on the amount of drug loading and zeta potential. Particle size and release efficiency was more affected by hydration temperature. The optimized formulation suggested by desirability of 93.5% was prepared using 1?mg of Sim, 10?mg of copolymer, dichloromethane as the organic solvent, hydration time of 45?min and hydration temperature of 25?°C. The release of the drug from nanomicelles was found to be biphasic and showed a rapid release in the first stage followed by a sustained release for 96?h. The gel-contained nanomicelles exhibited pseudo-plastic flow and more sustained drug release profile compared to nanomicelles. In excision wound model on normal rats, the wound closure of the group treated by Sim loaded micelles-gel was superior to other groups. Taken together, Sim loaded micelles-gel may represent a novel topical formulation for wound healing.     

Tableting of Eudragit RS and Propranolol Hydrochloride Solid Dispersion: Effect of Particle Size,Compaction Force,and Plasticizer Addition on Drug Release

The application of a solid dispersion (SD) system of propranolol HCl and Eudragit RS was evaluated in the preparation of prolonged release tablets. The effects of SD size fraction, compaction force, and inclusion of plasticizers [namely diethylphtalate (DEP) and triethylcitrate (TEC)] on crushing strengths of matrices and release profile of drug were also investigated. The results showed that when compressed as a tablet, the SD system was more efficient in prolonging drug release than physical mixture. This effect was due to formation of much harder tablets of the SD system (crushing strength 8.5 kg) compared with those of physical mixtures (crushing strength 2.7 kg). All matrices of the SD system showed release rate patterns that were best described by the Higuchi equation. It was also shown that the rate of drug release decreased from 19.8% to 9.13% min^??1/2 as the SD size fraction decreased from 300–350 to 125–250 µm. However, further reduction of size fraction did not significantly affect tablet crushing strength and drug release rate. Increase in compaction force from 5 to 30 kN increased the crushing strength of matrices from 2.9 to 13.6 kg. However, the rate of drug release remained nearly unchanged beyond compaction pressure of 10 kN, indicating that crushing strength of matrices in the range of 8.5–13.6 kg did not affect drug release rate. The addition of 5% or 10% of either plasticizer (DEP or TEC) led to an increase in crushing strength of matrices and more retardation of drug release. This effect was more pronounced for higher concentrations of plasticizers. This effect was probably due to more plastic deformation of matrices under the compaction force, which helped matrices to retain their shape throughout the dissolution test.     

Physicochemical properties and mechanisms of drug release from melt-extruded granules consisting of chlorpheniramine maleate and Eudragit FS

Abstract

The objective of this research project was to characterize the drug release profiles, physicochemical properties and drug–polymer interaction of melt-extruded granules consisting of chlorpheniramine maleate (CPM) and Eudragit® FS. Melt extrusion was performed using a single screw extruder at a processing temperature of 65–75?°C. The melt extrudate was milled, blended with lactose monohydrate and then filled into hard gelatin capsules. Each capsule contained 300?mg CPM granules. The release of CPM was determined with the United States Pharmacopeia dissolution apparatus II using a three-stage dissolution medium testing in order to simulate the pH conditions of the gastrointestinal tract. Pore structure, thermal properties and surface morphologies of CPM granules were studied using mercury and helium pycnometer, differential scanning calorimeter and scanning electron microscope. Sustained release of CPM over 10?h was achieved. The release of CPM was a function of drug loading and the size of the milled granules. The complexation between CPM and Eudragit® FS as the result of counterion condensation was observed, and the interaction was characterized using membrane dialysis and H¹ NMR techniques. In both 0.1?N HCl and phosphate buffer pH 6.8, CPM was released via a diffusion mechanism and the release rate was controlled by the pore structure of the melt-extruded granules. In phosphate buffer pH 7.4, CPM release was controlled by the low pH micro-environment created by CPM, the pore structure of the granules and the in situ complexation between CPM and Eudragit® FS.     

In vitro evaluation and in vivo performance of lyophilized gliclazide

Enhancement of the dissolution rate of the poorly water-soluble hypoglycemic agent, gliclazide, by the aid of lyophilization was investigated. Mannitol, sodium lauryl sulfate (SLS) and polyvinyl pyrrolidone (PVP-k-30) were employed in different weight ratios (43%, 56% and 64% w/w, respectively) as water-soluble excipients in the formulation. Lyophilized systems were found to exhibit extremely higher in vitro dissolution rate compared to the unprocessed drug powder. Solid state characterization of the lyophilized systems using X-ray powder diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry techniques revealed that dissolution enhancement was attributable to transformation of gliclazide from the crystalline to an amorphous state in the solid dispersion formed during the lyophilization process. The gastrointestinal absorption and hypoglycemic effect of the lyophilized gliclazide/SLS system were investigated following oral administration to Albino rabbits. C_max and area under the plasma concentration–time curve of gliclazide (AUC_0–12) after administration of the lyophilized formulations were significantly higher than those obtained after administration of the unprocessed gliclazide.     

Basic drug--enterosoluble polymer coevaporates: development of oral controlled release systems

Precipitation of basic drugs within oral prolonged release systems, at the higher pH values of the intestine, would affect drug release. Coevaporates of a model basic drug verapamil HCl, in single or mixed polymer systems, containing Eudragit L100 (L100) and ethyl cellulose or Eudragit RS100, were prepared from ethanolic solution. XRD and DSC indicated loss of crystallinity of the drug in the coevaporates. The presence of the enterosoluble polymer in the system was found to aid in faster dissolution of the drug at higher pH values. This was affected by the presence and type of retarding polymer present in the system. Compression of the coevaporates resulted in either very slow release of the drug or undesirable changes in the release profile. Pelletization of a coevaporate containing drug and L100 yielded systems, which released the drug uniformly when studied by the buffer change method in simulated gastric (SGF) and intestinal (SIF) fluids. The presence of L100 in intimate contact with the drug was found to be essential for the desirable drug release properties of the system. The drug release occurred predominantly by diffusion in SGF and by a combination of diffusion and polymer dissolution/erosion in SIF. Appropriate choice of release modifiers and formulation variables and development of suitable formulations can yield systems which compensate for the reduced solubility of the drug in the higher pH environments of the intestine.     

Emulsion/Solvent Evaporation as an Alternative Technique in Pellet Preparation

Paracetamol/Eudragit RS, paracetamol/ethylcellulose, and paracetamol/cellulose acetate pellets of different drug/polymer ratios (w/w) were prepared by the dissolution/solvent evaporation technique. These pellets were then characterized by particle size distribution analysis, ultraviolet (UV) spectroscopy, differential thermal analysis, and scanning electron microscopy (SEM). Hard gelatin capsules were filled with each particle size fraction of these pellets, and in vitro dissolution studies were performed to verify the capability of each series of pellets to control drug release. Pellets were spherical, presented a polynucleated microcapsule structure, and under certain experimental conditions, the yield of the preparation process reached very high values. The dissolution studies pointed out the slow paracetamol release from these pellets.     

Preparation and in vitro evaluation of meloxicam-loaded PLGA nanoparticles on HT-29 human colon adenocarcinoma cells

Context: The inhibitors of cyclooxygenase (COX)-2 play an important role in cancer chemoprevention. Certain COX-2 inhibitors exert antiproliferative and pro-apoptotic effects on cancer cells.

Objective: In this study, meloxicam, which is an enolic acid-type preferential COX-2 inhibitor, was encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) to maintain local high concentration, and its efficacy was determined.

Methods: NPs were prepared by using salting-out and emulsion-evaporation steps. Meloxicam-loaded NP formulations were evaluated with respect to the drug loading, particle size, polydispersity index, zeta potential, drug release rate, and residual poly(vinyl alcohol) (PVA) percentage. The effects of PLGA and PVA molecular weight variations on the physicochemical properties of NPs were investigated. Stability of meloxicam in NPs was assessed over 3 months. COX-2 expressing human colon adenocarcinoma cell line HT-29 was used in cellular uptake and viability assays.

Results: NPs had a spherical shape and a negative zeta potential, and their size ranged between 170–231?nm with a lower polydispersity index. NPs prepared with high molecular weight PLGA were shown to be physically stable over three months at 4°C. The increase in molecular weight of the polymer and emulsifier reduced the in vitro release rate of meloxicam from NPs. Meloxicam-loaded NPs showed cytotoxic effects on HT-29 cells markedly at 800 µM. Cancer cells had high uptake of coumarin-6-loaded NPs.

Conclusion: The PLGA NPs developed in this study can be a potentially effective drug delivery system of meloxicam for the treatment of colon cancer.     

Construction and in vitro/in vivo evaluation of 17-allylamino-17-demethoxygeldanamycin (17AAG)-loaded PEGylated nanostructured lipid carriers

In this study, the PEGylated nanostructured lipid carriers (PEG-NLC) were constructed for the intravenous delivery of 17-allylamino-17-demethoxygeldanamycin (17AAG). 17AAG-PEG-NLC was successfully prepared by the method of emulsion evaporation at a high temperature and solidification at a low temperature using a mixture of glycerol monostearate and PEG₂₀₀₀-stearate as solid lipids, and medium-chain triglyceride as the liquid lipid. The results revealed that the morphology of the NLC was spheroidal. The particle size, zeta potential and entrapment efficiency for 17AAG-PEG-NLC were observed as 189.4?nm, ?20.2 mV and 83.42%, respectively. X-ray diffraction analysis revealed that 17AAG existed as amorphous structures in the nanoparticles. In the in vitro release study, the 17AAG from 17AAG-PEG-NLC exhibited a biphasic release pattern with burst release initially and sustained release afterwards. In addition, 17AAG-PEG-NLC showed a significantly higher in vitro antitumor efficacy and longer retention time in vivo than 17AAG solution. These results indicated that 17AAG-PEG-NLC may offer a promising alternative to the current 17AAG formulations for the treatment of solid tumors.     

Preparation and evaluation of oleoyl-carboxymethy-chitosan (OCMCS) nanoparticles as oral protein carriers

Oleoyl-carboxymethy chitosan (OCMCS) nanoparticles based on chitosan with different molecular weights (50, 170 and 820 kDa) were prepared by self-assembled method. The nanoparticles had spherical shape, positive surface charges and the mean diameters were 157.4, 274.1 and 396.7 nm, respectively. FITC-labeled OCMCS nanoparticles were internalized via the intestinal mucosa and observed in liver, spleen, intestine and heart following oral deliverance to carps (Cyprinus carpio). Extracellular products (ECPs) of Aeromonas hydrophila as microbial antigen was efficiently loaded to form OCMCS–ECPs nanoparticles and shown to be sustained release in PBS. Significantly higher (P < 0.05) antigen-specific antibodies were detected in serum after orally immunized with OCMCS-ECPs nanoparticles than that immunized with ECPs alone and non-immunized in control group in carps. These results implied that amphiphilic modified chitosan nanoparticles had great potential to be applied as carriers for the oral administration of protein drugs.     

Stabilization and Target Delivery of Nattokinase Using Compression Coating

ABSTRACT

The aim of the work is to develop a new formulation in order to stabilize a nutraceutical enzyme Nattokinase (NKCP) in powders and to control its release rate when it passes through the gastrointestinal tract of human. NKCP powders were first compacted into a tablet, which was then coated with a mixture of an enteric material Eudragit® L100-55 (EL100-55) and Hydroxypropylcellulose (HPC) by direct compression. The activity of the enzyme was determined using amidolytic assay and its release rates in artificial gastric juice and an intestinal fluid were quantified using bicinchoninic acid assay. Results have shown that the activity of NKCP was pressure independent and the coated tablets protected NKCP from being denatured in the gastric juice, and realized its controlled release to the intestine based on in vitro experiments.