Preparation and in vitro release studies of thymosin-loaded PLA microspheres

To obtain a kind of convenient oral dosage form of protein, which can be fully absorbed and is efficient and safe, the thymosin-loaded PLA（polylactic acid） microspheres are prepared by the emulsification- solvent evaporation method and the orthogonal design is used to optimize the technology of preparation. The form of the medicament microspheres of thymosin are proved by differential thermal analysis （DTA）. The drug content is determined by the Lowry method, and the package ratio of medicament microspheres of thymosin and drug release in vitro are calculated. The results show that the average diameter and encapsulation efficiency of the product prepared according to the optimized formulation are 13. 8 μm and 80. 7%, respectively. The in vitro release behavior within 12 h can be described by the Higuchi equation with T1/2 = 295 rain. There are no significant changes in size distribution and residual drug contents after being stored at 25℃ and 40 ℃ for 90 d, respectively. Due to the fact that its thymosin content and package ratio meet the requirement, and its releasing half life is long, the thymosin-loaded PLA microsohere has a favorable application future.

Studies on in vitro release of cyclosporine A-loaded microspheres

Aim This study was to prepare cyclosporine A （CyA） microspheres （Ms） using 75：25 poly （D, L-lactide-co-glycolide） polymer （PLGA）, and to evaluate the in vitro release of the CyA microspheres. Methods CyA-Ms were prepared by an oil-inwater （o/w） emulsion solvent extraction/evaporation process and characterized for drug content, particle size, surface morphology, and differential scanning calorimeter （DSC）. Accelerated in vitro release of cyclosporine A from the mieropsheres was studied at various conditions, such as temperatures, surfactants, pH values and organic solvents for a short period. Results CyA-Ms were in spherical shape with average particle size of 50 μm and loading efficiency of 13.0%. The results of DSC measurements suggested that at the dry state, CyA did interact very strongly with the hydrophilic PLGA polymer. In vitro release test in various release medium showed slight increase of CyA-Ms release profiles under various conditions of temperatures, surfactants and pH values. However, dramatical increase of CyA-Ms release was seen in the medium containing 30% isopropanol. Conclusion It was demonstrated that CyA could be incorporated into polymeric Ms prepared from PLGA using a solvent evaporation technique. The release medium containing 30% isopropanol might be the ideal condition for CyA-PLGA microspheres in vitro quality control test.

Preparation, Characterization and in Vitro Release of Ciprofloxacin Polylactic Acid Microspheres

Aim Ciprofloxacin polylactic acid microspheres (CFX-PLA-MS) were preparedusing solvent evaporation method from a solid-in-oil-in-water emulsion system. Methods Orthogonalexperiment was used to optimize the method of CFX-PLA-MS preparation. Microspheres werecharacterized in terms of morphology, size, encapsulation efficiency, drug loading and in vitro drugrelease. Results The physical state of CFX-PLA-MS was determined by scanning electron microscopy(SEM) and differential scanning calorimetry (DSC) . Microspheres formed were spherical with smoothsurfaces. Drug was enveloped in microspheres without mixing physically with PLA. The averageparticle size was 280.80 ± 0.15 μm, with over 90% of microspheres falling in the range of 250 -390 μm. The encapsulation efficiency was 65.8% ± 0.58% and the drug loading was 34.1% ± 0.51% .In vitro release study revealed a profile of sustained release of Ciprofloxacin from CFX-PLA-MS. Theaccumulated release percentage and half-life (T_(1/2) of Ciprofloxacin microspheres were 84.0% in53.2 h, and 31.9 h, respectively. Higuchi equation was Q= -0.0043 + 0.003 9 t^(1/2), r = 0.9941.Conclusion Ciprofloxacin microspheres have been successfully prepared and sustained release of CFXfrom microspheres is achieved.

An accelerated method to evaluate thymopentin release from microspheres in vitro

To design an accelerated method to evaluate thymopentin release from PLGA microspheres in vitro. Microspheres were prepared by double emulsion technique, using poly（lactide-co-glycolide） （PLGA） as carrier. At higher medium temperature （45℃, 50℃ and 55℃）, an accelerated release testing in short time was studied and correlated with the conventional release （37℃） in vitro. The release in vitro of thymopentin from PLGA microspheres at 45 ℃, 50℃ and 55℃ was significantly accelerated （P 〈 0.05）. In particular, at 50℃, an accelerated release （30 h） of the hydrophilic peptide from the PLGA matrix was achieved and correlated well with the conventional release （30 d）. An accelerated release testing in vitro at higher temperature could be used to monitor thymopentin release from PLGA microspheres.

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.

FACTORS AFFECT THE RELEASE OF PSEUDOEPHDRINE HYDROCHLORIDE FROM THE UNCOATED CATION EXCHANGE RESIN-BASED DRUG DELIVERY SYSTEM IN VITRO

In this paper, it was investigated that the effect of parameters such as the ionic strength, pH, counter-ion type of release medium, particle size, and cross linkage of cation exchange resin on the release of model drug pseudoephedrine hydrochloride (PE) from uncoated drug-resin complex. The drug-resin complex was prepared by the reaction of PE with strongly acidic cation exchange resin (001×4, 001×7, 001×14). The result showed that the loading of PE increased with the increase of temperatures. The release of PE from drug-resin complex at 37℃ was monitored in vitro. From the experiments, it was found that the release rate of PE depends on the pH, composition of the releasing media, increased at lower pH media or with increase of ionic strength of media. Moreover, the release rate of PE was inversely proportional to the cross-linkage and particle size of the cation exchange resin.

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 in vitro Studies of Stealth PEGylated PLGA Nanoparticles as Carriers for Arsenic Trioxide

The aim of this study was to prepare arsenic trioxide （ATO）-loaded stealth PEGylated PLGA nanoparticles （PEG-PLGA-NPs） and to assess the merits of PEG-PLGA-NPs as drug carriers for ATO delivery. PEG-PLGA copolymer was synthesized with methoxypolyethyleneglycol （Mw=5000）, D, L-lactide, and glycolide by the ring-opening polymerization method. Amorphous ATO was transformed into cubic crystal form to increase its solu-bility in the organic solvent. ATO-loaded PEG-PLGA-NPs were prepared by the modified spontaneous emulsification solvent diffusion （SESD） method, and the main experimental factors influencing the characteristics of nanopar- ticles were investigated, to optimize the preparation. To confirm the escape of PEG-PLGA-NPs from phagocytosis by phagocytes, PEG-PLGA-NPs labeled rhodamine B uptake by murine peritoneal macrophages （MPM） were analyzed by flow cytometry. The results showed that the physicochemical characteristics of PEG-PLGA-NPs were affected by the type and concentration of the emulsifiers, polymer concentration, and drug concentration. ATO-loaded PEG-PLGA-NPs, with particle size of 120.8nm, zeta potential of-10.73mV, encapsulation efficiency of 73.6%, and drug loading of 1.36%, were prepared under optimal conditions. The images of transmission electron micros-copy （TEM） indicated that the optimized nanoparticles were near spherical and without aggregation or adhesion. The release experiments in vitro showed the ATO release from PEG-PLGA-NPs exhibited consequently sustained release for more than 26d, which was in accordance with Higuchi equation. The uptake of PEG-PLGA-NPs by MPM was found to decrease markedly compared to PLGA-NPs. The experimental results showed that PEG-PLGA-NPs were potential nano drug delivery carriers for ATO.

The Study of Dipivefrin Hydrochloride Ophthalmic Gel

Dipivefrin hydrochloride ophthalmic gel was prepared and the release test and the isolated cornea permeation test of the formulation in vitro were investigated. The release test of the formulation was studied by using permeable membrane. The content and the release amount of Dipivefrin hydrochloride from the gel base were measured by high performance liquid chromatography. The cornea permeation test of the formulation was studied by using isolated rabbit corneas. The formulation release behavior in vitro followed the first-order kinetic equation. The release amount of Dipivefrin hydrochloride raised significantly with less polymer in the formulation. The cornea permeation behavior of the drug in vitro followed the first-order kinetic equation. The eye irritancy of Dipivefrin hydrochloride gel is lower than that of eyedrops.

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.

Pharmaceutical Characteristics of Daunorubicin Stealth Liposomes

This report studied on pharmaceutical characteristics of the stealth liposome containing dau-norubicin (DNR). The shape, size, entrapment efficiency and stability of the daunorubicin stealth liposomes (DNRSL) were examined. Visible spectrophotometry and the HPLC method were established for determination of the DNR in the DNRSL. The release of DNR from DNRSL in HBS (pH 7.5) and rat serum at 37 oC were examined. The results showed that the DNRSL had high entrapment efficiency (>85%), small size and slow release.

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.

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

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.

Preparation and in vitro characterization of paclitaxel-loaded pH-responsive polymeric micelles based on poly(2-ethyl-2-oxazoline)-vitamin E succinate

To ensure the delivery of antitumor drugs to tumor site and quick release in tumor cells, we designed and prepared pH-sensitive polymeric micelles by combining cationic ring-opening polymerization of 2-ethyl-2-oxazoline （EOz） with vitamin E succinate （VES）, and then encapsulating paclitaxel （PTX） into the micelles self-assembled by poly（2-ethyl-2-oxazoline）-vitamin E succinate （PEOz-VES）. The structure of the synthesized PEOz-VES was confirmed by ^1H NMR spectrum, and the molecular weight measured by GPC was 1212 g/mol. The pKa of PEOz-VES with a low critical micelle concentration of （5.84±0.02） mg/L was determined to be 6.01. The PTX-loaded PEOz-VES polymeric micelles prepared by film hydration method were characterized to have a nanoscaled size of about 30 nm in diameter, a positive Zeta potential of 4.86 mV and uniform spherical morphology by TEM observation. The drug loading content and encapsulation efficiency were （2.63±0.16）% and （84.1±3.38）%, respectively. The in vitro release behavior of PTX from PEOz-VES micelles in PBS displayed pH-dependent pattern and was gradually accelerated with decrease of pH value, implying that the micelles could distinguish endo/lysosomal pH and tumor extracellular pH from physiological pH by accelerating drug release. Therefore, the designed PEOz-VES micelles might have significant promise for anti-cancer drug delivery.

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.

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.

Preparation and characterization of intestine PepT1-targeted calcium carbonate nanoparticles

To improve the oral absorption of poorly water-soluble drugs by overcoming the intestinal epithelium barrier, calcium carbonate nanoparticles targeting to intestine peptide transporter 1（Pep T1） were fabricated by modification of the surface of calcium carbonate nanoparticles with Gly-Sar. Gly-Sar-conjugated TPGS was successfully synthesized and characterized, and coumarin 6-loaded Gly-Sar modified calcium carbonate nanoparticles were then prepared and characterized to have a nano-scaled size of about 193 nm in diameter, cracked surface morphology under a scanning electron microscope, and high drug loading efficiency（60.5±5.9）%. Moreover, the Gly-Sar-modified calcium carbonate nanoparticles exhibited better drug loading stability during the process of their transcellular transport, and evidently enhanced intestinal absorption of poorly water-soluble agents. Therefore, the designed intestine Pep T1-targeted calcium carbonate nanoparticles might have a promising potential for oral delivery of poorly water-soluble drugs.

Preparation and characterization of intestinal transporter-targeted polymeric micelles

The intestinal epithelium is the main barrier to the oral delivery of poorly water-soluble drugs. Based on the specific transporters expressed on the apical membrane of the intestinal epithelium, novel polymer micelles targeting to the organic cation transporter 2（OCTN2） were constructed by combining carnitine conjugated poly（2-ethyl-2-oxazoline）-poly（D,L-lactide）（Car-PEOz-PLA） with monomethoxy poly（ethylene glycol）-poly（D,L-lactide）（mP EG-PLA）. The structure of the synthesized Car-PEOz-PLA was confirmed by -1H NMR, TLC and ammonium reineckate precipitation reaction, and the number-average molecular weight determined by GPC was 7260 g/mol with a low PDI of 1.44. Coumarin 6-loaded carnitine modified polymeric micelles prepared by film hydration method were characterized to have a nano-scaled size of about 31 nm in diameter, uniform spherical morphology, high drug loading content of 0.098%±0.03% and encapsulation efficiency of 92.67%±2.80%. Moreover, the carnitine-modified micelles exhibited the similar in vitro release behavior in SGF and SIF, and evidently enhanced intestinal absorption of poorly water-soluble agent. Therefore, the designed OCTN2-targeted micelles might have a promising potential for oral delivery of poorly water-soluble drugs.