Release of Nestorone from Biodegradable Rods System in vitro

To study the controlled effect of poly （lactic acid） （PLA）, poly lactic-coglycolic （PLGA） and ethylenediamine （EDA）-maleic anhydride （MAH） modified PLA （EMPLA） for in vitro release of nestorone, rods were prepared using the solvent evaporation method. Amount of drug release in vitro was determined by UV spectrophotometry. Effects of rods diameter, the molecular weight of PLA, the drug percentage and the hydrophilicity of polymers on the release of biodegradable nestorone rods in vitro were investigated. It is indicated that the controlled effect of the biodegradable rods for the release of nestorone in vitro is good. The amount of drug released every week from rods in different diameter is similar to one another. The amount of drug released every week and the accumulative drug released during 12 week were almost in direct proportion with the drug percentage of the rods. The amount of drug released every week is increased as the decreasing of PLA molecular weight. As the hydrophlicity of polymer is improved, the rate of drug release every week is accelerated. The studies show that the plausibility of controlled release of nestorone from PLA, PLGA and EMPLA rods imply the possibility of their application as a controlled delivery system for nestorone. The results show that the greater the molecular weight of PLA is, the slower its degradation is and the slower the drug released; the greater the percentage of nestorone is, the more quickly the drug release. An increase of the hydrophilicity of the polymers will increase their degradation rate and leads to a fast drug release. Anyhow, these rods systems should be further evaluated in vivo.

Chlorogenic acid loaded chitosan nanoparticles with sustained release property,retained antioxidant activity and enhanced bioavailability

In this study,chlorogenic acid(CGA),a phenolic compound widely distributed in fruits and vegetables,was encapsulated into chitosan nanoparticles by ionic gelation method.The particles exhibited the size and zeta potential of 210 nm and 33 mV respectively.A regular,spherical shaped distribution of nanoparticles was observed through scanning electron microscopy(SEM)and the success of entrapment was confirmed by FTIR analysis.The encapsulation efficiency of CGA was at about 59%with the loading efficiency of 5.2%.In vitro ABTS assay indicated that the radical scavenging activity of CAG was retained in the nanostructure and further,the release kinetics study revealed the burst release of 69%CGA from nanoparticles at the end of 100th hours.Pharmacokinetic analysis in rats showed a lower level of Cmax,longer Tmax,longer MRT,larger AUC0et and AUC0e∞for the CGA nanoparticles compared to free CGA.Collectively,these results suggest that the synthesised nanoparticle with sustained release property can therefore ease the fortification of food-matrices targeted for health benefits through effective delivery of CGA in body.

Preparation and evaluation of nattokinaseloaded self-double-emulsifying drug delivery system

In the present study,we prepared nattokinase-loaded self-double-emulsifying drug delivery system(SDEDDS)and investigated its preliminary pharmacodynamics.The type and concentration of oil phase,inner aqueous phase and emulsifier were screened to prepare optimum nattokinase-loaded SDEDDS.Next,the optimum formulations were characterized based on microstructure,volume-weighted mean droplet size,self-emulsifying rate,yield,storage stability,in vitro release and in vivo pharmacodynamics studies.The water/oil/watermultiple emulsions exhibited typicalmultiple structure,with relatively small volumeweighted mean droplet size 6.0±0.7μm and high self-emulsifying ability(self-emulsifying time<2 min).Encapsulation of nattokinase was up to 86.8±8.2%.The cumulative release of nattokinase within 8 h was about 30%,exhibiting a sustained release effect.The pharmacodynamics study indicated that nattokinase-loaded SDEDDS could significantly prolong the whole blood clotting time in mouse and effectively improve the carrageenan-induced tail thrombosis compared with nattokinase solution.Moreover,we showed that SDEDDS could successfully self-emulsify into water/oil/water multiple emulsions upon dilution in dispersion medium with gentle stirring and effectively protect nattokinase activity in gastric environment.Our findings suggested that SDEDDS could be a promising strategy for peptide and protein drugs by oral administration.

Intercalation of Amido Cationic Drug with Montmorillonite

The intercalation of drug molecules with montmorillonit （MMT） using Acyclovir （ACV） as the model drug was focused on. The optimum conditions were studied based on orthogonal design, such as intercalation time and temperature. The intercalation composites were characterized by X-ray diffraction （XRD）, Fourier transformed infrared （FT-IR）, and thermogravimetric analysis （TGA）. The experimental results reveal that ACV is successfully intercalated into the interlayers of MMT, The in vitro release experiments reveal that ACV is released from MMT steadily and pH dependent.

Development and in vitro/in vivo evaluation of controlled release provesicles of a nateglinide–maltodextrin complex

The aim of this study was to characterize the provesicle formulation of nateglinide(NTG)to facilitate the development of a novel controlled release system of NTG with improved efficacy and oral bioavailability compared to the currently marketed NTG formulation(Glinate^(™)60).NTG provesicles were prepared by a slurry method using the non-ionic surfactant,Span 60(SP),and cholesterol(CH)as vesicle forming agents and maltodextrin as a coated carrier.Multilamellar niosomes with narrow size distribution were shown to be successfully prepared by means of dynamic laser scattering(DLS)and field emission scanning electron microscopy(FESEM).The absence of drug-excipient interactions was confirmed by Fourier transform infrared spectroscopy(FT-IR),differential scanning calorimetry(DSC)and X-ray diffraction(XRD)studies.In vitro release of NTG in different dissolution media was improved compared to pure drug.A goat intestinal permeation study revealed that the provesicular formulation(F4)with an SP:CH ratio of 5:5 gave higher cumulative amount of drug permeated at 48 h compared to Glinate^(™)60 and control.A pharmacodynamic study in streptozotocin-induced diabetic rats confirmed that formulation F4 significantly(P<0.05)reduced blood glucose levels in comparison to Glinate 60.Overall the results show that controlled release NTG provesicles offer a useful and promising oral delivery system for the treatment of type Ⅱ diabetes.

PLGA nanoparticle encapsulated paclitaxol for sustained release and its anticancer effect for HeLa cells in vitro

Poly (D,L-lactide-co-glycolide) (PLGA) is a biodegradable and biocompatible polymer material for drug deliver system. The aim of this study is to synthesize drug-loaded

Release behavior and kinetic evaluation of berberine hydrochloride from ethyl cellulose/chitosan microspheres

Novel ethyl cellulose/chitosan microspheres （ECCMs） were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger than 5 pm. The drug loading efficiency of berberine hydrochloride （BH） loaded in microspheres were affected by chitosan （CS） concentration, EC concentration and the volume ratio of V（CS）/V（EC）. ECCMs prepared had sustained release efficiency on BH which was changed with different preparation parameters. In addition, the pH value of release media had obvious effect on the release character of ECCMs. The release rate of BH from sample B was only a little more than 30% in diluted hydrochloric acid （dHCl） and that was almost 90% in PBS during 24 h. Furthermore, the drug release data were fitted to different kinetic models to analyze the release kinetics and the mechanism from the microspheres. The released results of BH indicated that ECCMs exhibited non-Fickian diffusion mechanism in dHCI and diffusion-controlled drug release based on Fickian diffusion in PBS. So the ECCMs might be an ideal sustained release system especially in dHCl and the drug release was governed by both diffusion of the drug and dissolution of the polymeric network.

Physicochemical properties,antimicrobial activity and oil release of fish gelatin films incorporated with cinnamon essential oil

Fish skin gelatin films incorporated with various concentrations of cinnamon essential oil(CEO)were prepared and characterized.The results showed that tensile strength(TS),elongation at break(EAB),and water content(WC)of the gelatin based film decreased with the increasing concentrations of CEO,but water vapor permeability(WVP)increased.Addition of CEO improved light barrier property of the film.The Scanning electron microscope(SEM)showed that the heterogeneous surface and porous formation appeared in gelatin-CEO films.Fourier transform infrared spectroscopy analyses(FTIR-ATR)spectra indicated the interactions existed between gelatin and CEO.The gelatin-CEO films exhibited good inhibitory effects against the tested microorganisms(Escherichia coli,Staphylococcus aureus,Aspergillus niger,Rhizopus oryzae,and Paecilomyces varioti)and their antifungal activity seemed to be more effective than the resistance to bacterial growth.In vitro release studies showed an initial burst effect of CEO release and that subsequently slowed down at 40℃,but the initial burst release was not obvious at 4℃.The obtained results suggested that incorporation of CEO as a natural antimicrobial agent into gelatin film has potential for developing as active food packaging.

Controlled Drug Release Studies of Atenolol Using Differently Sulfonated Acryloxyacetophenone and Methyl Methacrylate Copolymer Resins as Drug Carriers

2-Acryloxyacetophenone （AAP） was prepared and subjected to suspension polymerization with methyl methacrylate （MMA） using azobisisobutyronitrile （AIBN） as free radical initiator. The differently sulfonated AAP-MMA cross-linked copolymer cationic exchange resins were prepared by sulfonation with concentrated sulphuric acid at 70 ~C. Several characteristics of the prepared resins were evaluated, i.e. FTIR, the ion-exchange capacity （IEC）, thermo gravimetric analysis （TGA）, particle size distribution and microscopic morphology. The resin characteristics were altered with degree of sulfonation, providing that differently sulfonated resins could be prepared. The behavior of atenolol （ATL） loading and in vitro release in the USP stimulated gastric and intestinal fluids of the obtained resins were evaluated. The drug loaded in the resin increased with increasing degree of sulfonation and hence the drug binding site in resin employed. The drug release was lower from the resins with higher content of sulfonic group due to the increase in the diffusive path depth. The drug release was a little lower in stimulated gastric fluid （SGF） than in stimulated intestinal fluids （SIF）. The basic groups, ionized to a little greater extent in SGF and preferred binding with the resin rather than releasing. Hence, the differently sulfonated resins could be utilized as novel carriers for drug delivery.

Formulation and evaluation of a bioadhesive patch for buccal delivery of tizanidine

Tizanidine hydrochloride(THCl)is an antispasmodic agent which undergoes extensive first pass metabolism making it a possible candidate for buccal delivery.The aim of this study was to prepare a monolayered buccal patch containing THCl using the emulsification solvent evaporation method.Fourteen formulations were prepared using the polymers Eudragit■ RS 100 or EudragitB RL 100 and chitosan.Polymer solutions in acetone were combined with a THCl aqueous solution(in some cases containing chitosan)by homogenization at 9000 rpm for 2 min in the presence of triethyl citrate as plasticizer and cast in novel Teflon molds.Physicochemical properties such as film thickness,in vitro drug release and in vitro mucoadhesion were evaluated after which permeation across sheep buccal mucosa was examined in terms of flux and lag time.Formulations prepared using a Eudragit■polymer alone exhibited sa tisfactory physicomechanical properties but lacked a gradual in vitro drug release pattern.Incorporation of chitosan into formulations resulted in the formation of a porous structure which did exhibit gradual release of drug.In conclusion,THCl can be delivered by a buccal patch formulated as a blend of Eudragit■ and chitosan,the latter being necessary to achieve gradual drug release.

Comparison Study of Chitosan/β-Cyclodextrin and Carboxymethyl Chitosan/β-Cyclodextrin Microspheres

To compare two microspheres of chitosan/β-cyclodextrin and carboxymethyl chitosan/β-cyclodextrin loaded theophylline as pulmonary sustained drug delivery carriers, the characteristics and ciliotoxicity were studied. The drug loadings of chitosan/ β-cyclodextrin and carboxymethyl chitosan/β-cyclodextrin micro- spheres were 21.09% and 21.42%, and the encapsulation efficiencies were 91.40% and 92.80%. The distributions of 50% （d0.5） of chitosan/β-cyclodextrin and carboxymethyl chitosan/β-cyclodextrin microspheres were 4.89 and 5.83 μm, respectively. Both micro- spheres showed spherical shape with smooth or wrinkled surfaces. FT-IR of chitosan/β-cyclodextrin microspheres demonstrated that theophylline had formed hydrogen bonds with chitosan and β-cyclodextrin, while for the carboxymethyl chitosan/β-cyclodextrin microspheres theophylline had interaction with carboxymethyl chitosan. The moisture absorption showed that an equilibrium was reached within 24 h. The two microspheres possessed better adaptability. In vitro release of theophylline from chitosan/ β-cyclodextrin microspheres was slower than that from carboxy- methyl chitosan/β-cyclodcxtrin microspheres at pH 6.8.

Design and evaluation of chitosan-amino acid thermosensitive hydrogel

Chitosan/glycerophosphate thermosensitive hydrogel crosslinked physically was a potential drug delivery carrier;however, long gelation time limits its application. Here, chitosan-amino acid (AA) thermosensitive hydrogels were prepared from chitosan (CS), αβ-glycerophosphate (GP), and L-lysine (Lys) or L-glutamic acid (Glu). The prepared CS-Lys/GP and CS-Glu/GP hydrogel showed good thermosensitivity and could form gels in a short time. The optimal parameters of CS-Lys/GP hydrogel were that the concentration of CS-Lys was 2.5%, the ratio of CS/Lys was 3.5/1.0, the ratio of CS-Lys/GP was 4.5/1.0. The optimal parameters of CS-Glu/GP hydrogel were that the concentration of CS-Glu was 3.0%, the ratio of CS/Glu was 2.0/1.0, and the ratio of CS-Glu/GP was 4.0/1.5. Chitosan-amino acid (CS-AA) thermosensitive hydrogel had a three-dimensional network structure. The addition of model drug tinidazole (TNZ) had no obvious effect on the structure of hydrogel. The results of infrared spectroscopy showed that there were hydrogen bonds between amino acids and chitosan. In vitro release results showed that CS-Lys/GP and CS-Glu/GP thermosensitive hydrogels had sustained release effects. Thus, the chitosan-amino acid thermosensitive hydrogels hold great potential as a sustained release drug delivery system.

Extraction of protein from churpi of yak milk origin:Size reduction,nutraceutical potential and as a wall material for resveratrol

Resveratrol is a known anti-oxidant and anti-cancer bioactive.The low bioavailability and poor water solubility of resveratrol is a major barrier that restricts its usage in food applications.To overcome these problems,the study presents micro and nano encapsulation of resveratrol in casein micelles extracted from Himalayan cheese(Churpi).Resveratrol loaded casein microparticles(CS-rm)were obtained using emulsion-freeze drying.Whereas,resveratrol loaded casein nanoparticles(CS-rn)were obtained using ultrasonication.Both were characterized using dynamic light scattering(DLS),scanning electron microscopy(SEM)and attenuated total reflectance-fourier transform infrared spectroscopy(ATR-FTIR).DLS revealed hydrodynamic diameter of 71.24μm and 387.023 nm and zeta potential of-22.62 and-28.08 mV for CS-rm and CS-rn.FTIR confirmed the characteristic peaks of resveratrol at 965.4,1380.86,1586.66 and 1607 cm-1 confirmed successful micro and nanoencapsulation.CS-rm displayed high encapsulation efficiency(52.32%)and swelling power(77.90 at pH 3 and 68.65 at pH 7.5)than CS-rn.Both micro and nanoencapsulation protected resveratrol in gastric conditions,however,CS-rn showed high release of resveratrol then CS-rm in simulated intestinal conditions.The anti-oxidant and anti-cancer activity of resveratrol under simulated gastric and intestinal conditions(SGID)was significantly higher(p≤0.05)for CS-rn,showing that nanoencapsulation improved release and nutraceutical profile of resveratrol.Resveratrol loaded nano and micro casein particles can be used a source of fortified protein supplement in growing food and nutraceutical industry.

A novel cataplasma matrix of traditional Chinese medicine

The aim of this paper was to develop a cataplasma matrix that can be applicable to both watersoluble and liposoluble drugs.The gellan gum and konjaku were employed as the scaffold materials of the matrix.With polyacrylic acid sodium and oligosaccharides as tacktifier,the formula of the cataplasma matrix was optimized in the orthogonal method as:gellan gum 0.4 g,xanthan gum 0.03 g,konjac glue 0.1 g,glycerin 4 g,Gluco-Adhesive T(GAT)6 g,Gluco-Adhesive E(GAE)6 g,polyacrylic acid sodium 0.22 g,and sorbitol 3 g.The 180°peel strength,the tensile strength and the elongation at break was 3.043 N,0.275 MPa and 91.05%,respectively.Furthermore,the drug-compatibilities of the matrix were investigated with baicalin,berberine and curcumin,which were used as the models of hydrophilic,poor-water-soluble and hydrophobic ingredients.The drug contents could reach 4.12%,2.42%and 3.75%,while the in vitro release rate were measured as,361.79,55.85 and 104.41μg·cm^(-2)·h^(-1)for baicalin,berberine and curcumin,respectively.These results indicated that the obtained matrix had good drug-compatibility and drug-release properties for different ingredients.