Intestinal Sac Technique Research Articles

Calcium-sensing receptor is not expressed in the absorptive enterocytes of weaned piglets.

The calcium-sensing receptor (CaSR) is a kokumi receptor that plays an essential role in nutrient sensing and animal physiology, growth, and development. Pig CaSR (pCaSR) was identified and characterized in the intestine. However, further research is still needed to confirm the expression of CaSR in the epithelial cells isolated from weaned piglets. In this study, primary enterocytes were isolated and characterized from the ileum of weaned piglets by the Weiser distended intestinal sac technique and fluorescence-activated cell sorting (FACS) based on sucrase-isomaltase (SI) as an enterocyte-specific marker. The expression of CaSR was investigated in both primary enterocytes and the intestinal porcine enterocyte cell line-j2 (IPEC-J2) by droplet digital polymerase chain reaction (ddPCR), immunofluorescence staining, and Western blotting. Results demonstrated that porcine enterocytes could be obtained using FACS with the SI as the enterocyte-specific marker and that pCaSR is not expressed in both porcine ileal enterocytes and IPEC-J2 cells, which specifically identified the expression of pCaSR in ileal enterocytes with sensitive and specific approaches.

Annona muricata L. extract decreases intestinal glucose absorption and improves glucose tolerance in normal and diabetic rats

Introduction: Poorly controlled hyperglycemia causes numerous health complications. Postprandial hyperglycemia is an important indicator of diabetic status. The aim of this research was to evaluate the effect of Annona muricata L. extract on the in vitro intestinal glucose absorption in diabetic rats and in vivo antihyperglycemic activity in both normal and diabetic rats. Methods: Phytochemical screening of the aqueous extract from the leaves of A. muricata was carried out. Albino rats were randomly assigned into normal and diabetic groups. Each group was divided into three subgroups: control (vehicle), experimental (A. muricata), and standard (Metformin) groups, to determine antihyperglycemic activity at different times after glucose overload. The everted intestinal sac technique was used to study intestinal glucose absorption in diabetic rats. Results: Aqueous leaf extract of Peruvian A. muricata exhibited statistically significant (P < 0.05) in vivo antihyperglycemic activity in both normal and diabetic rats when compared to the control group. The magnitude of the effect was similar to metformin treatment. Moreover, the aqueous leaf extract of A. muricata significantly diminished in vitro intestinal glucose absorption, with a magnitude similar to metformin treatment. Phytochemical analysis of the aqueous extract revealed the presence of tannins, flavonoids, alkaloids, and leucoanthocyanidins, among others. Conclusion: This study reveals that A. muricata aqueous extract is able to reduce in vitro intestinal glucose absorption and improve oral glucose tolerance in rats.

Antihyperglycemic potential of Gentianella gilgiana (Reimers) Fabris ex J.S. Pringle for in vitro intestinal glucose absorption in diabetic albino rats

Objective: To evaluate the antihyperglycemic potential of the Gentianella gilgiana (Reimers) Fabris ex J.S. Pringle infusion for in vitro intestinal glucose absorption in Rattus norvegicus of the Holtzman strain with chemically-induced diabetes. Materials and methods: The study had an experimental and analytical design. A phytochemical screening of the whole plant was carried out. For the in vitro study, twenty male albino rats were induced with diabetes using alloxan monohydrate (Sigma-Aldrich, Saint Louis, MO, USA) at a dose of 120 mg/kg bw administered by intraperitoneal route, and then randomly distributed into two groups of ten albino rats each. After ten days, they were sacrificed to extract an intestinal segment using the everted intestinal sac technique, and measure the glucose transport and absorption. In the control group (everted intestines incubated in Krebs-Henseleit solution containing glucose) and the experimental group (intestines incubated in Krebs-Henseleit solution containing glucose plus the Gentianella gilgiana (Reimers) Fabris ex J.S. Pringle infusion at 10% w/v), basal samples of fluids were taken from incubation, and then other samples were taken at 15, 30, 45 and 60 minutes to quantify the glucose from the mucous and serous compartments using the glucose oxidase enzymatic method.Results: Lower concentrations of absorbed glucose were observed in the intestinal serous compartment of the experimental group (G. gilgiana) with a statistically significant difference compared to the control group (p <0.05). Conclusions: The Gentianella gilgiana (Reimers) Fabris ex J.S. Pringle infusion exhibits a significant antihyperglycemic potential by decreasing the in vitro intestinal glucose absorption in diabetic albino rats.

Role of Alternative Lipid Excipients in the Design of Self-Nanoemulsifying Formulations for Fenofibrate: Characterization, in vitro Dispersion, Digestion and ex vivo Gut Permeation Studies.

Background: The choice of lipid excipients and their origin are crucial determinant factors in the design of self-nanoemulsifying drug delivery system (SNEDDS).Aim: To investigate the aspects of alternative excipients which can influence the development of efficient SNEDDS and determine the fate of fenofibrate in aqueous media.Methods: SNEDDS of two groups (a and b) were developed using Cremercoor MCT/Capmul MCM and Kollisolv MCT/Imwitor 742 blended oils and water soluble surfactants (to improve lipid polarity) for the model anti-cholesterol drug fenofibrate. Visual assessment was employed and droplet size measurement was taken into initial consideration for optimized SNEDDS. Further SNEDDS optimizations were done on the basis of maximum drug loading by equilibrium solubility studies and maximum solubilized drug upon aqueous dispersion by dynamic dispersion studies. In vitro lipolysis was examined under simulated Fed and Fasted conditions. Intestinal permeability study of the optimal SNEDDS formulation was compared with the raw fenofibrate dispersion using non- everted “intestinal sac technique.”Results: Initial characterization and solubility studies showed that mixed glycerides of Kollisolv MCT/Imwitor 742 (group b) containing formulations generated highly efficient SNEDDS as they are stable and produced lower nanodroplets with higher drug loading (group b) as compared to mixed glycerides of Cremercoor MCT/Capmul MCM (group a). In vitro dispersion and digestion studies confirmed that SNEDDS of group b (polar mixed glycerides) can retain high amount of drug (99% drug in solution for more than 24 h time) in dispersion media and have high recovery after digestion. The results from the permeability assessment confirmed that fenofibrate had 4.3-fold increase with F3b SNEDDS compared with the control.Conclusion: SNEDDS formulations containing alternative excipients (Kollisolv MCT/Imwitor 742 blend) could be a potential oral pharmaceutical product in taking anti-hyperlipidaemic agent fenofibrate to the systemic circulation as solubilized form.

Oral microemulsion of phytoconstituent found in licorice as chemopreventive against benzo(a)pyrene induced forestomach tumors in experimental mice model

Dibenzoylmethane (DBM), a minor phytoconstituent found in roots of licorice (Glycyrhiza glabra) has been reported to exhibit antioxidant and chemopreventive effects. It suffers from a problem of poor aqueous solubility and permeability leading to low oral bioavailability. Microemulsion, a novel colloidal carrier was proposed to improve its solubility in order to achieve enhanced oral biodistribution and efficacy. The microemulsion was prepared using peppermint oil and Tween 20 as oil phase and surfactant respectively. The spherical globules of microemulsion depicted a mean globule size of 157 nm and polydispersity index (PDI) of 0.715. The results of exvivo intestinal permeation using non everted intestinal sac technique demonstrated 5.7 time enhancement in intestinal permeability from microemulsion. During the invivo chemopreventive evaluations using benzo(a)pyrene [B(a)P] induced forestomach tumors in mice model, the treatment with DBM microemulsion, resulted in almost 100% reduction in tumor incidence after the last dose of B(a)P. The histopathological studies suggested the regression of stomach tumors after treatment with DBM microemulsion. Also, the biochemical estimations for oxidative stress markers depicted its improved efficacy in chemoprevention. The above results suggested that oral microemulsion formulation augmented the permeability and effectiveness of DBM as potential chemopreventive agent.

Self-emulsifying phospholipid pre-concentrates (SEPPs) for improved oral delivery of the anti-cancer genistein: Development, appraisal and ex-vivo intestinal permeation

Genistein (GEN), a potent anticancer agent, suffers from scanty oral bioavailability due to poor solubility and extensive metabolism. This work endeavored to enhance GEN solubility and intestinal permeability via fabrication of self-emulsifying phospholipid pre-concentrates (SEPPs) using some bioactive surfactants. Moreover, the potential of surfactant-free SEPP to address GEN obstacles was investigated. SEPPs were prepared from Phosal® 53MCT, oil/phosphatidylcholine mixture, alone or with only 30% of different surfactant/co-surfactant mixture (S/CO). In-vitro characterization encompassed globule size analysis, zeta potential (ZP), transmission electron microscopy, and in-vitro release. Ex-vivo intestinal permeation study was performed using non-everted rat intestinal sac technique. Upon aqueous dilution, SEPPs were easily dispersed with spherical globules within a nano-range size (from 165±15 to 425±20nm) and adequate negative ZP (>−30mV). SEPPs demonstrated a significant enhancement in GEN release compared to drug suspension without superior effect due to added S/CO. Permeation study revealed that at least 12.13% free GEN was permeated after 120min from SEPPs compared to only 3.7% from drug suspension. Among different SEPPs, SEPP containing 30% Tween 80/Transcutol HP mixture showed the highest GEN permeation (18.54%). Conclusively, SEPP might be a promising nanocarrier that enhances GEN bioavailability via improving dissolution and inhibition of pre-systemic clearance.

Ex-vivo absorption study of a nanoparticle based novel drug delivery system of vitamin D3 (Arachitol Nano™) using everted intestinal sac technique

Cholecalciferol, is a fat soluble vitamin D3 (Vit.D3), recognized in promoting bone health in children and adults and also it has other health benefits. Vit.D3 has suggested being dependent on bile salts for the formation of mixed micelles which is a pre requisite for its absorption. The efficiency of oral absorption of conventional Vit.D3 is approximately 50 %. Arachitol Nano™ is a commercially available nanoparticle based novel drug delivery system (NDDS) of Vit.D3. Data on the uptake of Vit.D3 from the NDDS (Arachitol Nano™) through the intestinal epithelium is not documented. The aim of the study was to investigate the absorption of a nanoparticle based NDDS of Vit.D3 (Arachitol Nano™) using everted rat intestinal sac technique. The results of the study suggested that Vit.D3 from Arachitol Nano™ showed a nonspecific absorption through various segments of rat small intestine, with high flux, permeability coefficient and percentage of absorption (79.21 ± 0.23, 76.55 ± 0.24 and 77.73 ± 0.24 % for duodenum, jejunum and ileum). The average absorption of Arachitol Nano™ was 77.83 ± 0.24 % through rat small intestine. The predicted human absorption may be more than 90 %. The study demonstrates that water soluble nanoparticle Vit.D3 (Arachitol Nano™) can substantially increase the oral absorption of the vitamin D3 and thus can be useful in the oral delivery of vitamin D3.

Reduced bioavailability of cyclosporine A in rats by mung bean seed coat extract

Mung bean seed coat (MBSC) is a healthcare product in Asian countries. The aim of this study was to investigate the effect of an MBSC ethanol extract on the bioavailability of cyclosporine A (CsA) in rats. Rats were orally dosed with CsA alone or in combination with MBSC ethanol extracts (500 mg/kg, p.o.). The blood levels of CsA were assayed by liquid chromatography with an electrospray ionization source and tandem mass spectrometry (LC-MS/MS). The everted rat intestinal sac technique was used to determine the influence of MBSC on the absorption of CsA. The results reveal that combined CsA intake with MBSC decreased the Cmax, AUC0-t, t1/2z and MRT0-t values of CsA by 24.96%, 47.28%, 34.73% and 23.58%, respectively (P&lt;0.05), and significantly raised the CL/F by 51.97% (P&lt;0.01). The in vitro results demonstrated that significantly less CsA was absorbed (P&lt;0.05). The overall results indicate that after being concomitantly ingested, MBSC reduced the bioavailability of CsA, at least partially, in the absorption phase.

Intestinal absorption of nutrients using rats fed different diets

Absorption of glucose, sucrose, glutamic acid, methionine, lysine and cysteine was studied using the intestinal everted sac technique. Rats were fed rice diets Basmati 370, Pusa Basmati 1 and Haryana Basmati 1 using as a casein control. Absorption of nutrients was monitored spectrophotometrically and of glucose, sucrose and glutamic acid by 14c radio assay using scintillation counting. Positive correlation coefficients between the two assay methods for glucose (r = 0.84), sucrose (r = 0.38) and glutamic acid (r = 0.80) were observed. Glucose showed higher absorption than sucrose and glutamic acid than lysine, cysteine and methionine. Absorption of glucose, sucrose and glutamic acid were higher in rats fed on Haryana Basmati 1 diet as demonstrated by both the methods. Rats on Basmati 370 diet exhibited higher methionine, lysine and cysteine absorption. Absorption of nutrients differed significantly between casein and rice.

Enhancement of absorption and hepatoprotective potential through soya-phosphatidylcholine-andrographolide vesicular system

Andrographis paniculata is a medicinal herb used extensively for various ailments and contains therapeutically active phytoconstituent, andrographolide (AN). Although hepatoprotective activity of AN is established, but their bioavailability is restricted due to its rapid clearance. The aim of this study, therefore, was to formulate AN herbosomes (ANH) through complexation with naturally occurring soya-phosphatidylcholine (SPC), in order to enhance absorption. Prepared andrographolide-soy phosphatidylcholine (AN-SPC) complex prepared was subjected for characterisation of complex and formation of vesicular system known as ANH using rotary evaporation techniques. This complex was subjected to in vitro study using everted small intestine sac technique which showed significantly increased absorption of AN from the ANH as compared to the plain AN. The hepatoprotective potential of ANH and plain AN was evaluated using carbon tetrachloride inducing hepatotoxicity rat model and compared, in which ANH equivalent to 50 mg/kg of plain AN significantly restore serum glutamate oxalacetate transaminase (112.4 ± 9.67 for AN whereas 90.2 ± 4.23 for ANH) and serum glutamate pyruvate transaminase (109.3 ± 7.89 for AN whereas 90.6 ± 4.34 for ANH) level as compared to control group. The ANH showed significantly better absorption than plain AN and this effect of ANH was also comparable to the standard drug (Silymarin). The findings of present study reveal that ANH has better bioavailability as shown by in vitro absorption study and hence improved hepatoprotection as compared to plain AN at equivalent dose.

Pharmacological evaluation of mangiferin herbosomes for antioxidant and hepatoprotection potential against ethanol induced hepatic damage

Context: Fatty liver is the first stage of alcoholic damage which is reversible with abstinence from alcohol. Mangiferin (MF) showed potent scavenging activity on diphenyl-1-picrylhydrazyl radicals which stimulate liver regeneration in various liver injuries.Objective: Although, MF shows hepatoprotection against various liver disorders but due to rapid clearance and limited solubility in lipoid environment, there is problem of its poor absorption from intestine hence poor bioavailability. Owing to which there is a need to develop MF herbosomes to resolve the problem of poor bioavailability to enhance the therapeutic potential.Methods: Successfully prepared MF herbosomes through complexation with phospholipids were characterized by physicochemical, chromatography, spectroscopy (differential scanning calorimetry (DSC), infrared (IR), and nuclear magnetic resonance (NMR)), ex vivo absorption using everted small intestine sac technique and in vivo studies using ethanol inducing hepatotoxicity in albino rats and comparing the results against plain MF.Results: Ex vivo study showed significant increased absorption of MF from prepared MF herbosomes as compared to plain MF. The hepatoprotective potential of MF herbosomes evaluated by in vivo study revealed significantly decreased levels of serum glutamate oxaloacetate transminase (SGOT), serum glutamate pyruvate transminase (SGPT), total bilirubin, and alkaline phosphatase (ALP) in MF herbosomes as compared to plain MF. MF herbosomes also showed significantly decreased level of malonyl dehydrogenase along with increased levels of reduced glutathione, superoxide dismutase (SOD) and catalase as compared to plain MF which was also comparable to the standard drug, silymarin (SL).Conclusion: The above mentioned results showed that hepatoprotective and antioxidant potency of MF enhanced due to the preparation of its herbosomes.

Development and evaluation of novel microemulsion based oral formulations of 5-fluorouracil using non-everted rat intestine sac model

Oral formulations of 5-fluorouracil (5-FU) with enhanced bioavailability were developed using microemulsion as a drug carrier system. The formulations were evaluated for drug content, physicochemical characteristics such as globule size, zeta potential, viscosity, stability and permeation characteristics. Ex vivo permeation studies were performed using non-everted rat intestinal sac technique. Results of the ex vivo permeation studies revealed that from aqueous solution only 25.08% drug was permeated, whereas, the optimized microemulsion formulation showed 97.5% drug permeation in 8 h, suggesting, approximately, four times enhancement in the drug permeability. Also a 7-fold increase in the flux of drug was observed from microemulsion formulation when compared with the aqueous solution. Further, in vivo pharmacodynamic studies were carried to check the therapeutic efficacy against benzo(a)pyrene [B(a)P]-induced stomach tumors in albino mice (Balb/C strain). The treatment of mice with 5-FU and microemulsion (5-FU II), after the last dose of B(a)P i.e. during the initiation period, resulted in 25% and 67% reduction in tumor incidence, respectively suggesting significant enhancement in the bioavailability and therapeutic efficacy of 5-FU when it was formulated as a microemulsion. These promising results suggest that microemulsion formulation of 5-FU may be used for the treatment of human cancers after pharmacokinetic and clinical evaluation.

Bioavailability Enhancement of Curcumin by Complexation with Phosphatidyl Choline

Curcumin is a major constituent of rhizomes of Curcuma longa. Pharmacokinetic studies of curcumin reveal its poor absorption through intestine. Objective of the present study was to enhance bioavailability of curcumin by its complexation with phosphatidyl choline (PC). Complex of curcumin was prepared with PC and characterized on the basis of solubility, melting point, differential scanning calorimetry, thin layer chromatography, and infrared spectroscopic analysis. Everted intestine sac technique was used to study ex vivo drug absorption of curcumin-PC (CU-PC) complex and plain curcumin. Pharmacokinetic studies were performed in rats, and hepatoprotective activity of CU-PC complex was also compared with curcumin and CU-PC physical mixture in isolated rat hepatocytes. Analytical reports along with spectroscopic data revealed the formation of complex. The results of ex vivo study show that CU-PC complex has significantly increased absorption compared with curcumin, when given in equimolar doses. Complex showed enhanced bioavailability, improved pharmacokinetics, and increased hepatoprotective activity as compared with curcumin or CU-PC physical mixture. Enhanced bioavailability of CU-PC complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the curcumin. The present study clearly indicates the superiority of complex over curcumin, in terms of better absorption, enhanced bioavailability, and improved pharmacokinetics.

Absorption enhancement of grape seed polyphenols by complexation with phosphatidyl choline

Grape seed polyphenols (GPP) are reported to have various biological effects along with strong antioxidant potential. Pharmacokinetic studies of GPP reveal its poor absorption through the intestine. The objective of the present study was to enhance bioavailability of GPP by its complexation with phosphatidyl choline. A complex of GPP was prepared with phosphatidyl choline and characterized on the basis of solubility, melting point, DSC, and IR. Everted intestine sac technique was used to study ex vivo drug absorption of GPP-PC complex and plain GPP. Pharmacokinetic studies were performed in rats and the hepatoprotective activity of GPP-PC complex was also compared with GPP and GPP-PC physical mixture in isolated rat hepatocytes. Analytical reports along with spectroscopic data revealed the formation of the complex. The results of ex vivo study show that the GPP-PC complex has significantly increased absorption compared with GPP, when given in equimolar doses. The complex showed enhanced bioavailability, improved pharmacokinetics, and increased hepatoprotective activity as compared to GPP or GPP-PC physical mixtures. Enhanced bioavailability of GPP-PC complex may be due to the amphiphilic nature of the complex, which greatly enhance the lipid miscibility of GPP. The present study clearly indicates the superiority of complex over GPP, in terms of better absorption, enhanced bioavailability, and improved pharmacokinetics.

Study on Zn Relative Concentration and State in Sheep Duodenum by XAFS

Synchrotron-based X-ray absorption fine structure (XAFS) spectroscopy is not widely used in animal science. The objective of this study was to employ the XAFS technique to determine changes in zinc absorption and concentrations in the sheep interstinal sac using different zinc sources. Forty-eight sheep were slaughtered and their duodena were dissected. The duodena were randomly assigned to six zinc sources (ZnO, ZnSO(4), ZnMet, ZnLys, ZnSO(4) + methionine, ZnSO(4) + lysine). Ten centimeters of duodenal sac midpiece was incubated for 40 min in vitro using the everted intestinal sac technique in culture medium containing zinc from different sources. The amount of zinc present was normalized to 4 mg. XAFS was used to analyze the relative concentration and oxidation state of zinc, and atomic absorption spectrometry (AAS) was used to verify zinc concentration. The results showed that, for increasing zinc concentrations, organic zinc was a better source than inorganic zinc. In addition, the zinc concentration achieved using ZnMet was higher than that for ZnO and ZnSO(4) (P < 0.05) as measured by atomic absorption spectroscopy. The results using XAFS were consistent with that of AAS. The states of organic zinc and inorganic zinc were identical after being incubated for 40 min. As observed in these experiments, organic zinc was more easily absorbed than inorganic zinc. Our data demonstrate that organic zinc was dissociated into ions and then absorbed as inorganic zinc. In our experiments, we are the first investigators to use XAFS spectroscopy to determine zinc absorption in the sheep duodenal wall. We observed reduced absorption of inorganic zinc in the presence of methionine or lysine. Taken together, we postulate that the optimal molar ratio of inorganic zinc and ligand requires further study.

Complexation with phosphatidyl choline as a strategy for absorption enhancement of boswellic acid

Boswellic acids (BAs) are isolated from oleo gum resin of Boswellia serrata and are reported to be effective as anti-inflammatory, hypolipidemic, immunomodulatory, and anti-tumor. Pharmacokinetic studies of boswellic acid reveal its poor absorption through the intestine. The objective of the present study is to enhance bioavailability of boswellic acid by its complexation with phosphatidylcholine. A complex of boswellic acid was prepared with phosphatidylcholine and characterized on the basis of solubility, melting point, TLC, and IR. An everted intestine sac technique was used to study ex-vivo drug absorption of boswellic acid-phosphatidylcholine (BA-PC) complex and plain boswellic acid. Anti-inflammatory activity of the complex was compared with boswellic acid in carrageenan-induced paw edema in rats. Hypolipidemic activity was also evaluated in Triton-induced hyperlipidemia. The complex was also converted into vesicles (phytosomes) and compared with other vesicular systems (liposomes and niosomes) by evaluating its anti-inflammatory effect. Analytical reports along with spectroscopic data revealed the formation of a complex. The results of ex-vivo study show that BA-PC complex has significantly increased absorption compared with boswellic acid, when given in equimolar doses. The complex showed better anti-inflammatory and hypolipidemic activity as compared to BA. Among all vesicular systems phytosomes showed maximum anti-inflammatory activity. Enhanced bioavailability of the BA-PC complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the boswellic acid. The present study clearly indicates the superiority of complex over boswellic acid, in terms of better absorption, enhanced bioavailability and improved pharmacokinetics.

Zonula Occludens-1 alterations and enhanced intestinal permeability in methotrexate-treated rats

The molecular mechanisms that underlie the methotrexate (MTX)-mediated disruption of intestinal barrier function have not been fully characterized. Epithelial barrier function is determined in large part by a multiprotein complex located at the most apical part of the lateral membrane, which is referred to as a tight junction (TJ). In the present study, we examined the alteration of zonula occludens-1 (ZO-1), which is a scaffolding protein that plays a pivotal role in the formation of TJs, to identify an additional molecular mechanism for epithelial barrier dysfunction. Male Wistar rats were administered MTX (15 mg kg(-1)) orally once daily for 3-5 days. Intestinal mucosal permeability was determined using the in vitro everted intestinal sac technique. Mucosal inflammation was assessed by myeloperoxidase activity and production of reactive oxygen species. Altered expression, tyrosine phosphorylation, and localization of ZO-1 were evaluated by RT-PCR, Western blotting, immunoprecipitation, and immunohistochemistry. A barrier function study revealed increased intestinal permeability in rats treated with MTX for 4 days, as indicated by enhanced fluorescein isothiocyanate-dextran flux. In addition, mucosal inflammation was linked to enhanced intestinal permeability. Quantitative analysis of ZO-1 expression showed the absence of significant differences in MTX-treated rats, whereas tyrosine dephosphorylation of ZO-1 was observed. Moreover, we also detected an obvious reduction of ZO-1 immunostaining along the apical membrane of intestinal villi. These results indicate that, in MTX-treated rats, ZO-1 alterations may contribute to disturbance of the TJ barrier, which leads to enhanced intestinal permeability.

Investigation of the improved effects of 2-hydroxypropyl-β-cyclodextrin on solubility, dissolution rate, and intestinal absorptive profile of tanshinone IIA in rats

In this paper, the effect of the chemically modified cyclodextrin [namely, 2-hydroxypropyl-beta-cyclodextrin, (HP-beta-CD)] on the aqueous solubility, dissolution rate, and intestinal permeability of the tanshinone IIA (TS) was investigated. The corresponding inclusion complex of TS-HP-beta-CD at the molar ratio of 1:1 was obtained by coevaporation. The solubility of complexed TS in water at 37+/-0.1 centi-degree was 17 times greater than that for the uncomplexed drug. The dissolution rate of TS was significantly increased by the complexation with HP-beta-CD, due to its solubilizing activity. The everted intestinal sac technique in rats was used to study the absorption behavior studies of TS and this complexation through the intestinal tissues. The permeability rates of TS across the intestinal epithelial membrane were enhanced by the formation of inclusion complex with HP-beta-CD about 89, 97 and 82 times of the uncomplexed TS in duodenum, jejunum and ileum, respectively. It was revealed that the absorption rate-limiting step of TS might be the dissolution process. The present results indicated the potential use of HP-beta-CD to improve the gastrointestinal tract absorption of TS.

Complexation of tanshinone IIA with 2-hydroxypropyl-β-cyclodextrin: Effect on aqueous solubility, dissolution rate, and intestinal absorption behavior in rats

In this paper, the effect of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) on the aqueous solubility, dissolution rate, and intestinal permeability of the tanshinone IIA (TS IIA) was investigated. The corresponding inclusion complex of TS IIA/HP-β-CD at the molar ratio of 1:1 was obtained by coevaporation and characterized by differential scanning calorimetry, and X-ray diffraction. The solubility of complexed TS IIA in water at 37 ± 0.1 °C was 17 times greater than that for the uncomplexed drug. The dissolution rate of TS IIA was significantly increased by the complexation with HP-β-CD, due to its solubilizing activity. The everted intestinal sac technique in rats was used to study the absorption behavior of TS IIA and this complexation through the intestinal tissues. The permeability rates of TS IIA across the intestinal epithelial membrane were enhanced by the formation of inclusion complex with HP-β-CD about 5.2, 5.8 and 4.8 times of the uncomplexed TS IIA in duodenum, jejunum and ileum, respectively. It was revealed that the absorption rate-limiting step of TS IIA might be the dissolution process. The present results indicate the potential use of HP-β-CD to improve the gastrointestinal tract absorption of TS IIA.

Kinetic analysis of hexose transport to determine the mechanism of amygdalin and prunasin absorption in the intestine

Evidence is accumulating that glucose-conjugated compounds may be carried across the gut mucosa via the epithelial sodium-dependent monosaccharide transporter SGLT1. A modification of the everted intestinal sac technique was utilized to study the transport of the cyanogenic glycoside amygdalin (D-mandelonitrile beta-D-gentiobioside) and its metabolite D-mandelontrile beta-D-glucoside (prunasin). Everted sacs of rat jejunum and ileum were bathed in isotonic oxygenated sodium chloride-potassium phosphate buffer containing 2.8 microCi D-[(3)H]-mannose and 0.187 microCi D-[(14)C]-glucose. For treatment groups, buffers contained phloridzin, galactose, amygdalin or prunasin. The rate constant (k) for the transport process was calculated. Compared with the control (n = 33), phloridzin (n = 25) significantly reduced the rate constants of both D-[(14)C]-glucose and D-[(3)H]-mannose. Substitution of sodium with choline and incremental galactose treatments similarly reduced D-[(14)C]-glucose influx, indicating that a fraction of the transport is carrier-mediated. Treatment with amygdalin did not significantly affect the rate constants of D-[(14)C]-glucose or D-[(3)H]-mannose transport. However, treatment with 1 mM prunasin (n = 16) did reduce the influx of D-[(14)C]-glucose without affecting D-[(3)H]-mannose values. This is consistent with the reports finding that glycoside absorption may be mediated by SGLT1.