Drug release from xyloglucan beads coated with Eudragit for oral drug delivery

Xyloglucan (XG), which exhibits thermal sol to gel transition, non-toxicity, and low gelation concentration, is of interest in the development of sustained release carriers for drug delivery. Drug-loaded XG beads were prepared by extruding dropwise a dispersion of indomethacin in aqueous XG solution (2 wt.-%) through a syringe into corn oil. Enteric coating of XG bead was performed using Eudragit L 100 to improve the stability of XG bead in gastrointestinal (GI) track and to achieve gastroresistant drug release. Release behavior of indomethacin from XG beads in vitro was investigated as a function of loading content of drug, pH of release medium, and concentration of coating agent. Adhesive force of XG was also measured using the tensile test. Uniform-sized spherical beads with particle diameters ranging from 692 +/- 30 to 819 +/- 50 microm were obtained. The effect of drug content on the release of indomethacin from XG beads depended on the medium pH. Release of indomethacin from XG beads was retarded by coating with Eudragit and increased rapidly with the change in medium pH from 1.2 to 7.4. Adhesive force of XG was stronger than that of Carbopol 943 P, a well-known commercial mucoadhesive polymer, in wet state. Results indicate the enteric-coated XG beads may be suitable as a carrier for oral drug delivery of irritant drug in the stomach.     

Design and evaluation of novel pH-sensitive chitosan nanoparticles for oral insulin delivery

Chitosan nanoparticles (CS NPs) have been commonly regarded as potential carriers for the mucosal delivery of therapeutic peptides because of their biocompatibility, bioadhesion and permeation enhancing properties. However, they have limited colloidal stability and readily dissociate and dissolve in the acidic gastric conditions. In the current study, CS NPs were formulated by ionic cross-linking with hydroxypropyl methylcellulose phthalate (HPMCP) as a pH-sensitive polymer and evaluated for the oral delivery of insulin. In vitro results revealed a superior acid stability of CS/HPMCP NPs with a significant control over insulin release and degradation in simulated acidic conditions with or without pepsin. Furthermore, fluorescently-labeled CS/HPMCP NPs showed a 2- to 4-fold improvement in the intestinal mucoadhesion and penetration compared to CS/TPP NPs as evidenced by quantitative fluorescence analysis and confocal microscopy. After s.c. injection to rats, no significant difference in the hypoglycemic effect of insulin solution or insulin-loaded CS/HPMCP NPs was observed, confirming the physico-chemical stability and biological activity of the entrapped peptide. Following peroral administration, CS/HPMCP NPs increased the hypoglycemic effect of insulin by more than 9.8 and 2.8-folds as compared to oral insulin solution and insulin-loaded CS/tripolyphosphate (TPP) NPs, respectively.     

Preparation of alginate/chitosan microcapsules and enteric coated granules of mistletoe lectin

The aqueous extract of European mistletoe (Viscum album, L.) has been used in cancer therapy. The purified mistletoe lectins, main components of mistletoe, have demonstrated cytotoxic and immune-system-stimulating activities. Korean mistletoe (Viscum album L. coloratum), a subspecies of European mistletoe, has also been reported to possess anticancer and immunological activities. A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. coloratum agglutinin, VCA) with Mr 60 kDa was isolated from Korean mistletoe. Mistletoe preparations have been given subcutaneously due to the low stability of lectin in the gastrointestinal (GI) tract. In the present study, we investigated the possibility of alginate/chitosan microcapsules as a tool for oral delivery of mistletoe lectin. In addition, our strategy has been to develop a system composed of stabilizing cores (granules), which contain mistletoe lectin, extract or powder, coated by a biodegradable polymer wall. Our results indicated that successful incorporation of VCA into alginate/chitosan microcapsules has been achieved and that the alginate/chitosan microcapsule protected the VCA from degradation at acidic pH values. And coating the VCA with polyacrylic polymers, Eudragit, produced outstanding results with ideal release profiles and only minimal losses of cytotoxicity after manufacturing step. The granules prepared with extract or whole plant produced the best results due to the stability in the extract or whole plant during manufacturing process.     

Pharmaceutical evaluation of genistein-loaded pluronic micelles for oral delivery

The purpose of the present study was to determine whether Pluronic F127 polymeric micelles could improve the oral bioavailability of a poor water-soluble drug, such as genistein. Genistein is a phytoestrogen that has estrogenic activity. F127 triblock copolymer consists of PEO100-PPO65-PEO100. Genistein was incorporated in the Pluronic F127 polymeric micelles by a solid dispersion method. The genistein release of genistein-loaded polymeric micelles was studied in vitro (in pH 1.2 and pH 6.8). And the oral bioavailabilities of genistein powder and genistein-loaded micelles were estimated at a dose of 4.0 mg/kg as genistein in rats. Drug loading amount and drug loading efficiency were 11.18% and 97.41%, respectively. The average size of the genistein-loaded polymeric micelles was 27.76 nm. And genistein release of the genistein-loaded polymeric micelles in vitro was 58% (pH 1.2) and 82% (pH 6.8). The bioavailability of genistein-loaded polymeric micelles was better than genistein powder. Consequently, Pluronic F127 polymeric micelles are an effective delivery system for the oral administration of genistein.     

Preparation,characterization, and evaluation in vivo of Ins-SiO2-HP55 (insulin-loaded silica coating HP55) for oral delivery of insulin

Insulin is the most effective and durable drug in the treatment of advanced stage diabetes. However, oral delivering insulin was a tough task for rapid enzymatic degradation. In this work, we designed and developed a delivery system composed of enteric nanosphere for oral delivery of insulin. The silica was selected for loading insulin, which surface has a lot of pores with a powerful adsorption capacity, advantages for permeability and slow-release. The insulin-loaded silica (Ins-SiO₂) was prepared by adsorption in HCl solution. The Ins-SiO₂ obtained was coated with the hydroxypropyl methylcellulose phthalate (HP55) by desolvation method, which is a good enteric coating material. The Ins-SiO₂-HP55, an enteric nanosphere of insulin obtained were characterized by transmission electron microscope (TEM), surface area, Fourier-transform infrared (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The results showed that insulin was loaded most in the pores of silica, while the HP55 coated on the extent of Ins-SiO_2. In vitro drug release results revealed that the release of insulin from Ins-SiO₂-HP55 was markedly reduced in simulated gastric fluid (SGF). By contrast, the release amount of insulin from Ins-SiO₂-HP55 was increased significantly in simulated intestinal fluid (SIF). In vivo evaluation on diabetic animals showed the blood glucose level of diabetic rats could be effectively reduced after oral administration Ins-SiO₂-HP55. There is marked hypoglycemic effect after 1 h of taking the Ins-SiO₂-HP55. After 3 h, the GLU of rats of the Ins-SiO₂-HP55 stably kept from 4.85 to 2.67 mmol/L that was significantly less than the normal level (6.7 mmol/L). However, that of rats taking raw insulin kept from 8.03 to 6.56 mmol/L that is higher than the normal level. These results suggested that Ins-SiO₂-HP55 could have potential value in oral administration systems of diabetes chemotherapy.     

pH- and sugar-sensitive layer-by-layer films and microcapsules for drug delivery

The present review provides an overview on the recent progress in the development of pH- and sugar-sensitive layer-by-layer (LbL) thin films and microcapsules in relation to their potential applications in drug delivery. pH-sensitive LbL films and microcapsules have been studied for the development of peptide and protein drug delivery systems to the gastrointestinal tract, anti-cancer drugs to tumor cells, anti-inflammatory drugs to inflamed tissues, and the intracellular delivery of DNA, where pH is shifted from neutral to acidic. pH-induced decomposition or permeability changes of LbL films and microcapsules form the basis for the pH-sensitive release of drugs. Sugar-sensitive LbL films and microcapsules have been studied mainly for the development of an artificial pancreas that can release insulin in response to the presence of glucose. Therefore, glucose oxidase, lectin, and phenylboronic acid have been used for the construction of glucose-sensitive LbL films and microcapsules. LbL film-coated islet cells are also candidates for an artificial pancreas. An artificial pancreas would make a significant contribution to improving the quality of life of diabetic patients by replacing repeated subcutaneous insulin injections.     

甲硝唑微囊口服结肠定位给药系统的制备

目的 :考察甲硝唑微囊口服结肠定位给药系统的制备工艺。方法 :采用液中干燥法制备微囊 ,应用均匀试验设计 ,考察各因素水平对微囊包封率、载药量的影响。按优化后的结果选择实验条件 ,进行重复实验 ,用体外溶出实验考察其结肠定位释放效果。结果 :制备的甲硝唑微囊包封率为 ( 62 .3± 1.3 ) % ,载药量为 ( 5 9.8± 2 .0 ) % ,所制备的片剂在 0 .1mol·L- 1 盐酸溶液和 pH6.8磷酸盐缓冲液中几乎不释放 ,而在 pH7.5磷酸盐缓冲液中 3 0min的平均累积释放量为 82 .13 %。结论 :优化后的制备工艺对甲硝唑微囊口服结肠定位给药系统的研究和应用具有一定的参考价值。     

新型茶碱口服结肠靶向给药系统的体内动力学

目的研究以时间为释药开关的结肠靶向给药系统。方法以非pH依赖型聚丙烯酸树脂Eu dragit NE 3 0D为膜材 ,制备茶碱薄膜衣片 ;用HPLC法进行体内血药浓度分析 ;以γ 闪烁照相研究该制剂体内胃肠道的转运情况。结果本制剂与参比制剂主要药代动力学参数分别为 :tlag( 8 67± 1 0 4 )h、( 0 67± 1 1 5 )h ;Cmax( 5 2 5± 1 2 1 )mg/L、( 4 0 9± 1 2 5 )mg/L ;AUC0 2 6 ( 2 7 5 0±7 2 0 )mg·h/L、( 3 9 0 4± 1 0 4 3 )mg·h/L ;体内γ 闪烁照相研究表明 ,体外 6 5h释放的制剂口服8 0h后到达升结肠处开始释药 ,且体内释药与体外释药有一定的相关性。结论本制剂能达到结肠靶向释药的设计要求     

Preparation and in vitro characterization of amifostine biodegradable microcapsules.

The purpose of this project was to develop sustained release microcapsules of amifostine. The microcapsules were prepared using solvent evaporation technique. The effect of several formulation variables on the characteristics of the microcapsules was studied. The formulation variables studied were drug loading, polymer (polylactide-co-glycolide) (PLGA) concentration, and the amount of gelatin in the initial aqueous phase. The drug loading was studied at three different levels (5, 10, and 25 mg); the PLGA concentration was studied at two levels (500 and 1000 mg); and the amount of gelatin used ranged from 2 to 14 mg. In general, the microcapsules were less than 155 microm in diameter with median size between 50 and 80 microm. While the use of higher amounts of PLGA significantly increased the median size of the microcapsules, using higher amounts of amifostine had no significant effect, irrespective of the amount of PLGA. The use of gelatin, within the range 2-14 mg, did not show any significant effect on the particle size distribution. Scanning electron microscopy (SEM) of the microcapsules revealed that all nine formulations yielded spherical particles. The use of 500 mg PLGA with 10 or 25 mg amifostine yielded microcapsules with porous surfaces. The surface pores, however, were not present in microcapsules prepared using 1000 mg PLGA. The efficiency of encapsulation decreased significantly from 63 to 24% when the amount of amifostine increased from 5 to 25 mg in the formulations using 500 mg PLGA. Similarly, the efficiency of encapsulation decreased from 87 to 23% when the amount of PLGA was doubled to 1000 mg. An increase in the amount of amifostine in the formulation using 500 mg PLGA also resulted in a significant increase in initial drug release (from 20 to 62%) within the first hour. These results were consistent with the porous morphology of these microcapsules. In general, all batches of microcapsules showed 24-96 h sustained drug release.     

Thiolated chitosan: Development and in vivo evaluation of an oral delivery system for leuprolide

The aim of the present study was to develop an oral delivery system for the peptide drug leuprolide. Gel formulations based on unmodified chitosan/reduced glutathione (GSH) and chitosan-thioglycolic acid (chitosan-TGA)/GSH were prepared, and their effect on the absorption of leuprolide was evaluated in vitro and in vivo in male Sprague Dawley rats. Transport studies were performed with freshly excised rat intestinal mucosa mounted in Ussing-type chambers. Due to the addition of gel formulations comprising 0.5% (m/v) unmodified chitosan/0.5% (m/v) GSH and 0.5% (m/v) chitosan-TGA/0.5% (m/v) GSH, the transport of leuprolide across excised mucosa was improved up to 2.06-fold and 3.79-fold, respectively, in comparison with leuprolide applied in buffer (P_app = 2.87 ± 0.77 × 10⁻⁶ cm/s).In vivo, the addition of oral gel formulation comprising 8 mg of unmodified chitosan, 1 mg of GSH and 1 mg of leuprolide increased the area under the plasma concentration-time curve (AUC_0-8) of leuprolide 1.39-fold in comparison with leuprolide having been administered just in saline. Moreover, the administration of oral gel formulation comprising 8 mg of chitosan-TGA, 1 mg of GSH and 1 mg of leuprolide resulted in a further enhanced leuprolide plasma concentration, and the area under the plasma concentration-time curve (AUC_0-8) of leuprolide was increased 3.72-fold in comparison with the control. With the oral gel formulation comprising 8 mg of chitosan-TGA, a relative bioavailability (versus s.c. injection) of 4.5% was achieved in contrast to the control displaying a relative bioavailability of 1.2%. Thus, according to the achieved results, it is suggested that chitosan-TGA in combination with GSH is a valuable tool for improving the oral bioavailability of the peptide drug leuprolide.     

Using microemulsion formulations for oral drug delivery of therapeutic peptides

Peptide drugs are increasingly becoming a very important class of therapeutic agents with the rapid advances in the field of biotechnology engineering. However, these drugs are generally not suitable for oral administration. In this review, the main physico-chemical and biopharmaceutical characteristics of peptides are summarized. The obstacles to peptide drug absorption and the different possibilities for solving these difficulties are listed. Results using this formulation approach for oral drug delivery of peptides are apparently promising with some specific peptides such as cyclosporin. Various mechanisms are only beginning to be understood and further investigations need to be performed in this area to explain the results obtained with some peptides.     

喷雾干燥法制备红霉素肠溶缓释微囊

目的：采用喷雾干燥法制备红霉素肠溶缓释微囊,并考察其释放特性。方法：以红毒素为囊心物,Eudragit S100为包衣材料,蓖麻油为增塑剂,乙醇为溶剂,将囊心物与囊材按1：2,1：3和1：4的比例喷雾干燥制备微囊。结果：经电镜扫描和X－射线衍射测定表明,囊心物：囊材按1：4比例制备的微囊外形圆整,包囊安全;体外释放度测定显示,微囊能稳定地在人工肠液中缓慢释放,药物1h释放量不超过30％,12h释放量不低于90％,与市售红霉素肠溶片相比,有明显缓释作用。结论：喷雾干燥法制备微囊,工艺稳定,可持续操作,可连续操作,制备的红霉素微囊有很好的肠溶行为缓释特征。     

Preparation and evaluation of ketoprofen floating oral delivery system

A sustained release system for ketoprofen designed to increase its residence time in the stomach without contact with the mucosa was achieved through the preparation of floating microparticles by the emulsion-solvent diffusion technique. Four different ratios of Eudragit S100 (ES) with Eudragit RL (ERL) were used to form the floating microparticles. The drug retained in the floating microparticles decreased with increase in ERL content. All floating microparticle formulations showed good flow properties and packability. Scanning electron microscopy and particle size analysis revealed differences between the formulations as to their appearance and size distribution. X-ray and DSC examination showed the amorphous nature of the drug. Release rates were generally low in 0.1 N HCl especially in presence of high content of ES while in phosphate buffer pH 6.8, high amounts of ES tended to give a higher release rate. Floating ability in 0.1 N HCl, 0.1 N HCl containing 0.02% Tween 20 and simulated gastric fluid without pepsin was also tested. The formulation containing ES:ERL1:1 (FIII) exhibited high percentage of floating particles in all examined media.     

The in vivo fate of nanoparticles and nanoparticle-loaded microcapsules after oral administration in mice: Evaluation of their potential for colon-specific delivery

Anti-cancer drug loaded-nanoparticles (NPs) or encapsulation of NPs in colon-targeted delivery systems shows potential for increasing the local drug concentration in the colon leading to improved treatment of colorectal cancer. To investigate the potential of the NP-based strategies for colon-specific delivery, two formulations, free Eudragit® NPs and enteric-coated NP-loaded chitosan–hypromellose microcapsules (MCs) were fluorescently-labelled and their tissue distribution in mice after oral administration was monitored by multispectral small animal imaging. The free NPs showed a shorter transit time throughout the mouse digestive tract than the MCs, with extensive excretion of NPs in faeces at 5 h. Conversely, the MCs showed complete NP release in the lower region of the mouse small intestine at 8 h post-administration. Overall, the encapsulation of NPs in MCs resulted in a higher colonic NP intensity from 8 h to 24 h post-administration compared to the free NPs, due to a NP ‘guarding’ effect of MCs during their transit along mouse gastrointestinal tract which decreased NP excretion in faeces. These imaging data revealed that this widely-utilised colon-targeting MC formulation lacked site-precision for releasing its NP load in the colon, but the increased residence time of the NPs in the lower gastrointestinal tract suggests that it is still useful for localised release of chemotherapeutics, compared to NP administration alone. In addition, both formulations resided in the stomach of mice at considerable concentrations over 24 h. Thus, adhesion of NP- or MC-based oral delivery systems to gastric mucosa may be problematic for colon-specific delivery of the cargo to the colon and should be carefully investigated for a full evaluation of particulate delivery systems.     

Formulation and characterization of an oily-based system for oral delivery of insulin

The present work explored the possibility of formulating an oral insulin delivery system by combining the advantages of nanoencapsulation and the use of oily vehicle. The parameters affecting formulation such as association efficiency were characterized. The preparation was evaluated for its chemical, physical and biological stability. The preparation has unimodal particle size distribution with a mean diameter of 108 ± 9 nm. Insulin was protected from gastric enzymes by incorporation into lipid-based formulation. The results of RP HPLC and ELISA indicated that insulin was able to withstand the preparation procedure. Insulin in the preparations was stable for a period of one month at storage temperatures of 4 and 25 °C. It was also biologically active and stable as demonstrated by the remarkable reduction of blood glucose levels of the STZ-diabetic rats after oral administration of the preparation. Moreover, hypoglycemic effect of nanoparticles administered orally was sustained for a longer period of time compared to the subcutaneous injection. These results clearly evidenced the ability of the nanoparticles to enhance the pharmacological response of insulin when given orally and could be used to deliver other peptides.     

Chitosan–aprotinin coated liposomes for oral peptide delivery: Development, characterisation and in vivo evaluation

In order to improve the systemic uptake of therapeutic peptides/proteins after oral administration, the polymer-protease inhibitor conjugate chitosan–aprotinin was synthesised and polyelectrolyte complexes between negatively charged multilamellar vesicles (MLV) and positively charged chitosan–aprotinin conjugate were prepared. It could be demonstrated that chitosan–aprotinin was capable of significantly inhibiting Trypsin in vitro in concentrations of 0.05% and 0.1%, whereas no inhibition was observed in the presence of 0.1% chitosan. The size range of the prepared MLV was between 3 and 4.5 μm and the initially negative zeta potential (ca. −90 mV) of the core liposomes switched to a positive value after polymer coating (ca. +40 mV). Confocal laser microscopy studies showed comparable mucoadhesive properties of chitosan–aprotinin coated MLV and chitosan coated MLV. In comparison to calcitonin in solution, the area above the blood calcium concentration–time curve (AAC) after oral administration of calcitonin loaded chitosan coated MLV to rats increased around 11-fold, and around 15-fold in the case of calcitonin loaded chitosan–aprotinin coated MLV. Data gained in the current study are believed to contribute to the development of novel polymer-protease inhibitor based delivery systems.     

In vitro and in vivo evaluation of WGA-carbopol modified liposomes as carriers for oral peptide delivery

Surface modification of liposomal nanocarriers with a novel polymer-lectin conjugate was proposed for enhancing the systemic uptake of encapsulated peptide and protein therapeutics after oral administration. Wheat germ agglutinin (WGA) was covalently attached to carbopol (CP) using the carbodiimide method. The prepared WGA-CP conjugate retained the biological cell binding activity of WGA without any evidence of cytotoxicity to Caco-2 monolayers. Cationic liposomes in the size range of 100 nm were prepared by the lipid film hydration method followed by probe sonication and surface modification with negatively charged WGA-CP. The uptake of WGA-CP liposomes by Caco-2 cells was significantly higher than that of non-modified or CP liposomes. The uptake was dependent on the surface concentration of WGA, temperature, and incubation period and was significantly inhibited in the presence of chlorpromazine and 10-fold excess of free WGA. These results suggest the involvement of active transport mechanism for the cellular uptake of the modified liposomes, mediated mainly by binding of WGA to its specific cell membrane receptors. Dual channel confocal microscopy confirmed the simultaneous association and internalization of the polymer conjugate and the liposomal carrier by Caco-2 cells and intestinal membrane of rats. In addition, the pharmacological efficacy of calcitonin, a model peptide drug, was enhanced by more than 20- and 3-fold following peroral administration of calcitonin-loaded WGA-CP liposomes when compared to non-modified and CP liposomes, respectively.     

Colon targeting: an emerging frontier for oral insulin delivery

Subcutaneous administration of insulin is associated with several limitations such as discomfort, local pain, irritation, infections, immune reactions and lipoatrophy as well as lipohypertrophy manifestations at the injection site. To overcome these drawbacks, enormous research is currently going on worldwide for designing of an alternative noninvasive route of administration. Pulmonary and oral route seem to be the most promising ones, with respect to the market value. However, after the letdown by pulmonary delivery of insulin, oral colon targeted delivery of insulin has gained tremendous interest among researchers. Although bioavailability remains a challenge for oral colon specific delivery of insulin, the employment of protease inhibitors, permeation enhancers and polymeric delivery systems have proved to be advantageous to overcome the said problem. This Editorial article is not intended to offer a comprehensive review on drug delivery, but shall familiarize the readers with the strategies employed for attaining non-erratic bioavailability of insulin, and to highlight some of the formulation technologies that have been developed for attaining oral colon-specific delivery of insulin.     

海藻酸包衣的季铵化壳聚糖纳米粒用于胰岛素口服给药的研究

本研究的目的是开发海藻酸包衣的壳聚糖纳米粒口服递送胰岛素。采用三聚磷酸钠（TPP）离子交联作用将N-[（2-羟基-3-三甲基铵）丙基]壳聚糖氯化物（HTCC）制备得到季铵化壳聚糖纳米粒（HTCC-T纳米粒）,然后在温和搅拌条件下滴加入海藻酸钠溶液,进一步形成海藻酸包衣季铵化壳聚糖纳米粒（HTCC-A纳米粒）。分别采用粒度仪、透射电镜和HPLC分析对HTCC-A纳米粒进行了粒径、zeta电位、表面形态、载药量和包封率的表征。结果表明,HTCC-A纳米粒为均匀的球形颗粒,大小为（322.2±8.5）nm,表面带有正电荷（（14.1±0.6）mV）。体外释放结果表明,在不同p H值的释放介质中,HTCC-A纳米粒的释放行为与HTCC-T纳米粒（未用海藻酸包衣）有很大的不同,这表明海藻酸包衣可以显著改善纳米粒中胰岛素的释放行为。同时,体外酶解试验和圆二色散图谱进一步证实,海藻酸包衣可以显著改善纳米粒中胰岛素结构稳定性。HTCC-A纳米粒十二指肠给药的相对药理生物利用度为8.0%±2.5%。与HTCC-T纳米粒口服给药相比,HTCC-A纳米粒的相对药理生物利用度显著增加（P〈0.05）,是HTCC-T纳米粒的2.2倍。由此可见,海藻酸包衣季铵化壳聚糖纳米粒（HTCC-A纳米粒）将可能成为一种有效的口服递送载体系统用于提高胰岛素的体内口服吸收效果。     

Preliminary evaluation of a novel oral delivery system for rhPTH1-34: in vitro and in vivo

rhPTH1-34 is clinically used for osteoporosis treatment. However, this peptide drug has no oral bioavailability because of proteolysis and low membrane permeability in gastrointestinal gut. This study explored the possibility of absorption enhancement for rhPTH1-34 through the oral delivery of the microemulsion. The microemulsion (85:15, oil/water) consisting of Labrasol, Crodamol GTCC, Solutol^® HS 15, d-α-tocopheryl acetate (6:2:1:1, w/w) and saline water was developed and characterized, including particle size, morphology, drug loading efficiency and permeability, stability and pharmacokinetics. The microemulsion showed high drug loading efficiency (83%) and permeability, and significantly higher resistance to proteolysis in vitro study. The relative oral bioavailability was 5.4% and 12.0% when delivered to gastric and ileum. Besides, osteoporosis rats were induced and treated with oral rhPTH1-34 microemulsion (0.05 mg/kg), injection (0.01 mg/kg) and vehicle, respectively, for 8 weeks. The proximal tibia bone mineral content and density in oral rats (0.188 ± 0.008 g, 0.283 ± 0.014 g/cm²) was significantly increased compared to the control rats (0.169 ± 0.006 g, 0.266 ± 0.011 g/cm²), reaching to the sham rats. And the proximal tibia microstructure of oral rats was improved greatly, approaching sham level too. These findings revealed that oral microemulsion may represent an effective oral delivery system for rhPTH1-34.