Intestinal Fluid Research Articles

Evaluation of Medicago sativa ethanol leaf extract for antidiarrheal activity in Wistar rats

Aim: Medicago sativa leaf is traditionally used for the treatment of gastrointestinal disorders in Nigeria. This research investigates the in vivo antidiarrheal activity of M. sativa (Alfalfa) leaf extract in Wistar rats. Method: The study employed three models: castor oil-induced diarrhea, gastrointestinal motility (charcoal meal), and castor oil-induced intestinal fluid accumulation. The phytochemical analysis as well acute toxicity tests were carried out in the leaf extract. Results: The results demonstrate a dose-dependent and significant antidiarrheal effect of M. sativa leaf extract. In the castor oil-induced diarrhea model, the extract reduced fecal frequency, delayed onset, and lowered severity, with the highest effect at 600 mg/kg compared to a positive control (Loperamide). Gastrointestinal motility was inhibited by the extract in a dose-dependent manner, achieving maximum effect at 600 mg/kg, comparable to atropine sulfate. The castor oil-induced intestinal fluid accumulation model revealed a significant decrease in fluid volume at 600 mg/kg, exhibiting a potent inhibitory effect. The oral LD50 values obtained were greater than 5000 mg/kg in rats Conclusion: This study provides compelling evidence of Medicago sativa leaf extract's potential as an antidiarrheal agent in Wistar rats. Further investigations could explore its mechanism of action and safety profile, contributing valuable insights to the development of novel antidiarrheal therapies.

Prospect of Gum Arabic-Cocoliposome Matrix to Encapsulate Curcumin for Oral Administration.

Curcumin is an antioxidant that can effectively eliminate free radicals. However, as its oral bioavailability is low, an effective delivery method is required. Phospholipid-based liposomes can encapsulate lipophilic drugs, such as curcumin, while liposome, cholesterol, and gum Arabic (GA) can enhance the internal and external stability of drug membranes. This present study used concentrations of cholesterol (Cchol) and GA (CGA), ranging from 0 to 10, 20, 30, and 40% as well as 0 to 5, 10, 15, 20, 30, and 40%, respectively, to encapsulate curcumin in a GA-cocoliposome (CCL/GA) matrix and test its efficacy in simulated intestinal fluid (SIF) and simulated gastric fluid (SGF). The absence of new characteristic peaks in the Fourier transform infrared (FTIR) spectra results indicate the presence of non-covalent interactions in the CCL/GA encapsulation. Furthermore, increasing the Cchol decreased the encapsulation efficiency (EE), loading capacity (LC), and antioxidant activity (IR) of the CCL/GA encapsulation but increased its release rate (RR). Conversely, increasing CGA increased its EE and IR but decreased its LC and RR. The two conditions applied confirmed this. Liposomal curcumin had the highest IR in SIF (84.081%) and the highest RR in SGF (0.657 ppm/day). Furthermore, liposomes loaded with 10% Cchol and 20% CGA performed best in SIF, while those loaded with 10% Cchol and 30% CGA performed best in SGF. Lastly, the CCL/GA performed better in SIF than SGF.

In vitro release dynamics of doxorubicin hydrochloride & gentamicin sulphate through nanoparticle embedded sterculia gum/gelatin self crosslinked hydrogel system

Present study synthesized stimuli-sensitive drug delivery systems for anti-cancer drug doxorubicin hydrochloride (Dox) and antibiotic drug gentamicin sulphate (GS) using sterculia gum, gelatin, and Fe3O4 nanoparticles. The approach involved oxidizing sterculia gum with NaIO4, followed by self-crosslinking with gelatin resulting a pH-responsive protein hybrid crosslinked network. Further gel matrix was reinforced with Fe3O4 nanoparticles resulted in magnetic nanocomposite hydrogel. FTIR, powdered XRD, and FESEM had been used to characterize the functionalized drug-loaded hydrogels. In vitro release behavior of Dox and GS had been studied in pH 2.2, 7.0, 7.4, simulated gastric fluid (SGF) and in simulated intestinal fluid (SIF). For both drugs, highest release had been achieved in pH 2.2 and SGF, while minimum in physiological pH 7.4. The release mechanisms adopted by Dox and GS from drug loaded OSG-cl-Gelatin and OSG-cl-Gelatin/Fe3O4 matrix have been assessed using different mathematical models viz Zero order, First order, Higuchi kinetic model and Korsmeyer Peppas model in different release mediums. Drug release mainly had occurred through Case-II diffusion mechanism. In acidic pH, Dox release followed Higuchi kinetic model while GS release occurred through Korsmeyer Peppas model. Hydrolytic degradation potential, thrombogenicity and haemocompatible behavior of functionalized gel matrix had also been screened.

The Synthesis of Broccoli Sprout Extract-loaded Silk Fibroin Nanoparticles as Efficient Drug Delivery Vehicles: Development and Characterization

Targeted drug delivery of biological molecules using the development of biocompatible, non-toxic, and biodegradable nanocarriers can be a promising method for cancer therapy. In this study, silk fibroin protein nanoparticles (SFPNPs) were synthesized as a targeted delivery system for sulforaphane-rich broccoli sprout extract (BSE). The BSE-loaded SFPNPs were conjugated with polyethylene glycol and folic acid, then their physicochemical properties were characterized via UV-Vis, XRD, FTIR, DLS, FE-SEM, and EDX analyses. In vitro release profile, antioxidant and anticancer activities of NPs were also studied. The FE-SEM and DLS analyses indicated stable NPs with an average size of 88.5 nm and high zeta potential (-32 mV). The sulforaphane release profile from NPs was pH-dependent, with the maximum release value (70%) observed in simulated intestinal fluid (pH = 7.4). Encapsulation of BSE also decreased the release rate of sulforaphane from the capsules compared to the free BSE. In vitro cytotoxicity of BSE and NPs on breast cancer cell lines (MCF-7) were concentration-dependent, and IC50 for BSE and NPs were acquired in 54 and 210 μg mL−1, respectively. Moreover, the NPs demonstrated no appreciable cytotoxicity in normal mouse fibroblast (L929) cell lines. These results indicated that biocompatible NPs synthesized as controlled and long-term targeted drug delivery systems can be a potential candidate for breast cancer therapy.

Bacillus subtilis SOM8 isolated from sesame oil meal for potential probiotic application in inhibiting human enteropathogens

BackgroundWhile particular strains within the Bacillus species, such as Bacillus subtilis, have been commercially utilised as probiotics, it is critical to implement screening assays and evaluate the safety to identify potential Bacillus probiotic strains before clinical trials. This is because some Bacillus species, including B. cereus and B. anthracis, can produce toxins that are harmful to humans.ResultsIn this study, we implemented a funnel-shaped approach to isolate and evaluate prospective probiotics from homogenised food waste – sesame oil meal (SOM). Of nine isolated strains with antipathogenic properties, B. subtilis SOM8 displayed the most promising activities against five listed human enteropathogens and was selected for further comprehensive assessment. B. subtilis SOM8 exhibited good tolerance when exposed to adverse stressors including acidity, bile salts, simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and heat treatment. Additionally, B. subtilis SOM8 possesses host-associated benefits such as antioxidant and bile salt hydrolase (BSH) activity. Furthermore, B. subtilis SOM8 contains only haemolysin toxin genes but has been proved to display partial haemolysis in the test and low cytotoxicity in Caco-2 cell models for in vitro evaluation. Moreover, B. subtilis SOM8 intrinsically resists only streptomycin and lacks plasmids or other mobile genetic elements. Bioinformatic analyses also predicted B. subtilis SOM8 encodes various bioactives compound like fengycin and lichendicin that could enable further biomedical applications.ConclusionsOur comprehensive evaluation revealed the substantial potential of B. subtilis SOM8 as a probiotic for targeting human enteropathogens, attributable to its exceptional performance across selection assays. Furthermore, our safety assessment, encompassing both phenotypic and genotypic analyses, showed B. subtilis SOM8 has a favourable preclinical safety profile, without significant threats to human health. Collectively, these findings highlight the promising prospects of B. subtilis SOM8 as a potent probiotic candidate for additional clinical development.

Preparation and application of curcumin loaded with citric acid crosslinked chitosan-gelatin hydrogels

While oral administration offers safety benefits, its therapeutic efficacy is hindered by various physiological factors within the body. In this study, a novel approach was explored using a matrix consisting of 2 % chitosan and 2 % gelatin, with citric acid (CA) serving as a green cross-linking agent (ranging from 0.4 % to 1.0 %), and curcumin (Cur) as the model drug to formulate hydrogel carriers. The results showed that a 0.4 % CA concentration, the hydrogel (CGA0.4) reached swelling equilibrium in deionized water within 40 min, exhibiting a maximum swelling index was 539 g/g. The addition of Cur to the CGA hydrogel (CGACur) notably enhanced release efficiency, particularly in simulated intestinal fluid, where Cur release rates exceeded 40 % within 100 min compared to below 8 % in other solutions. Among these hydrogels, CGA0.4Cur exhibited the fastest degradation rate in the combined solution, reaching >90 % degradation after 7 days. Additionally, Cur and CA demonstrated positive effects on the tensile strength, antioxidant activity and antibacterial activity of hydrogels. Compare to the bioaccessibility of CGC (27 %), those of CGACur had increased to over 34 %. These findings offer provide theoretical support for CA-crosslinked chitosan/gelatin gels in delivering hydrophobic bioactive molecules and their application in intestinal drug delivery system.

The Impact of Polymers on Enzalutamide Solid Self-Nanoemulsifying Drug Delivery System and Improved Bioavailability.

Enzalutamide (ENZ), marketed under the brand name Xtandi® as a soft capsule, is an androgen receptor signaling inhibitor drug actively used in clinical settings for treating prostate cancer. However, ENZ's low solubility and bioavailability significantly hinder the achievement of optimal therapeutic outcomes. In previous studies, a liquid self-nanoemulsifying drug delivery system (L-SNEDDS) containing ENZ was developed among various solubilization technologies. However, powder formulations that included colloidal silica rapidly formed crystal nuclei in aqueous solutions, leading to a significant decrease in dissolution. Consequently, this study evaluated the efficacy of adding a polymer as a recrystallization inhibitor to a solid SNEDDS (S-SNEDDS) to maintain the drug in a stable, amorphous state in aqueous environments. Polymers were selected based on solubility tests, and the S-SNEDDS formulation was successfully produced via spray drying. The optimized S-SNEDDS formulation demonstrated through X-ray diffraction and differential scanning calorimetry data that it significantly reduced drug crystallinity and enhanced its dissolution rate in simulated gastric and intestinal fluid conditions. In an in vivo study, the bioavailability of orally administered formulations was increased compared to the free drug. Our results highlight the effectiveness of solid-SNEDDS formulations in enhancing the bioavailability of ENZ and outline the potential translational directions for oral drug development.

Exploration of the method and efficacy of treatments for intractable pelvic pain caused by rectal or bladder fistula

Objective: To explore the causes and therapeutic effects of pelvic pain caused by rectal fistula or bladder fistula after comprehensive treatment of cervical cancer and rectal cancer (radiotherapy, surgery, chemotherapy, and other treatments). Methods: A retrospective analysis was conducted on the clinical and pathological data of patients with pelvic tumors admitted to the First People's Hospital of Yinchuan City, Ningxia and the Affiliated Cancer Hospital of Zhengzhou University from June 2016 to June 2022. The causes of persistent pelvic pain in patients after comprehensive treatment was investigated, and the corresponding therapeutic effects after clinical treatment was observed. Results: Thirty-two tumor patients experienced persistent pain after comprehensive treatment, including 22 cases of cervical cancer and 10 cases of rectal cancer. The preoperative pain of the entire group of patients was evaluated using the digital grading method, with a pain score of (7.88±1.31) points. Among the 32 patients, there were 16 cases of rectovaginal fistula or ileovaginal fistula, 9 cases of vesicovaginal fistula, 5 cases of rectoperineal fistula, and 2 cases of vesicovaginorectal fistula. Thirty-two patients were initially treated with medication to relieve pain, and according to the ruptured organs, a fistula was made to the corresponding proximal intestinal canal and renal pelvis to intercept the intestinal contents and urine. However, the pain did not significantly be improved. The pain score of treatment with the above methods for one week was (8.13±1.13) points, and there was no statistically significant difference compared to preoperative treatment (P=0.417). In the later stage, based on a comprehensive evaluation of whether the tumor had recurred, the value of organ preservation, the benefits of surgery, the balance between survival time and improving quality of life, pathological organ resection or repair was performed. The surgical methods included repair of leaks, local debridement combined with irrigation of proximal intestinal fluid, distal closure of the sigmoid colon combined with proximal ostomy, posterior pelvic organ resection, anterior pelvic organ resection, and total pelvic organ resection. One week after surgery, the patients' pain completely relieved or disappeared, with the pain score of (1.72±1.37) points, which was significantly divergent from the preoperative and initial surgical treatments (P＜0.001). Conclusions: Palliative pyelostomy and proximal enterostomy cannot effectively alleviate persistent pelvic floor pain. The fundamental way to alleviate pain is complete blocking of the inflammatory erosion of the intestinal fluid and urine.

A method for treatment of deep and superficial enteroatmospheric fistulas in an open abdomen, ChimneyVAC: Ten years experience.

Leakage of intestinal fluid is a challenging event when it appears in an open abdomen (OA) and surgical deviation does not seem possible. Intestinal contents in the abdominal cavity maintain inflammation and drainage is there for essential. We have developed a method, ChimneyVAC, to treat both deep and superficial enteroatmospheric fistulas (EAF) AIMS: To describe this innovative surgical technique and our 10-year experience. This single-center observational cohort study included all 16 consecutive patients treated with ChimneyVAC. Seven women and 9 men; median age: 47; (interquartile range [IQR]:39-63) years, 15 with a small bowel fistula and 1 with a large bowel fistula. All except of the colonic fistula were classified as a high output fistula; 14 were deep and 2 superficial. In this technique, a negative-pressure source is applied directly above the fistula opening, in addition to negative pressure wound therapy for the OA. This controls the leakage of intestinal fluid by direct drainage into a vacuum system, thereby avoiding contamination of the abdomen. A controlled enterocutaneous fistula (ECF) then forms as the traction from the ChimneyVAC brings the fistula opening to skin level. In 14 patients, an ECF formed after a median of 42 (IQR:28-55) days and 12 (IQR:7-16) dressing changes. The median length of hospitalization was 103 (IQR:58-143) days. Two patients died of multiorgan failure and 14 initially survived. This study showed that 14 out of 16 patients survived the initial treatment for enteric leakage with the ChimneyVAC method. The outcome of ChimneyVAC treatment is a controlled ECF, which was then corrected after a median of six months. However, hospitalization is lengthy, the patients undergo several dressing changes and many needs additional parenteral nutrition until intestinal continuity is reestablished. ChimneyVAC is a feasible method for treatment of EAF in an OA, with favorable survival.

Surviving process and transit: Controlled freeze drying, storage and enteric coated capsules for targeted delivery of probiotic Lactobacillusacidophilus

Viability loss of probiotics often occur during processing, storage and gastrointestinal transit. In this study, the viability of freeze-dried Lactobacillus acidophilus LA-5® was assessed after controlled freeze drying and storage at 4 °C and 25 °C over six months using glycerol, skim milk and trehalose as protectants. The freeze-dried probiotic was filled into hard gelatin capsules and enteric coated with the co-polymer Eudragit L100-55 using a fluidised bed coater to determine if the freeze-dried probiotic will survive the enteric coating process and remain viable during gastric transit. Empty hard gelatin capsules were also enteric coated by dipping in the co-polymer solution. These were dried, filled with microcrystalline cellulose and tested for their resistance to simulated gastric condition. The results showed that controlled freezing of the probiotic bacteria did not cause significant loss in viability when the cells were cryopreserved in the protectants. Viable cell loss was greater during the drying stage. Relatively better cell survival was recorded when the freeze-dried samples that were cryopreserved with skim milk were stored over six months at 4 °C. Freeze-dried samples that were preserved with trehalose stored better at 25 °C. The results also demonstrated that capsules coated with Eudragit L100-55 did not disintegrate in simulated gastric fluid. However, the capsules disintegrated in a simulated intestinal fluid. The enteric coating process resulted in about 95% recovery of viable cells. The high viable cell recovery after the coating process is likely due to the coating solution and conditions impacting the capsule body and cap rather than the cells directly. The study highlights that enteric coated capsules can offer gastric protection whilst minimizing viability losses associated with the enteric coating process.

A Research Work on Design, Development and In-Vitro Evaluation of Losartan Potassium Loaded Pectinate Microspheres

One of the special and innovative drug delivery strategies is the use of microspheres, which can increase a drug's effectiveness by preventing drug dilution in bodily fluids, allowing drug localization and targeting at a specific site, and maintaining drug concentration between MEC and MTC levels.Microspheres are characterized as roughly spherical, solid particles with sizes between 1 to 1000 μm that are intended to be covered in protective materials such as polymeric or waxy coatings. One of the more innovative methods in the field of oral controlled drug delivery systems is the use of microsphere dosage forms, which target a specific area of the body for a prolonged period of time, allowing for more effective local drug delivery as well as improved systemic drug. The % yield of all the losartan potassium loaded pectinate microsphere formulations (LM1 to LM5) was found within the range from 76.74 ± 3.79 % to 89.06 ± 2.67 %.The % entrapment efficiency and particle size of the prepared losartan potassium loaded pectinate microsphere formulations (LM1 to LM5) was found within the range from 63.68 ± 3.55 % to 84.78 ± 2.27 % and 0.78 ± 0.14 mm to 0.91 ± 0.05 mm respectively. Formulations LM1 to LM5 showed 2.12 % to 12.46 % mucoadhesion up to 6 hours in simulated gastric fluid (pH 1.2, 0.1N HCl) and 74.28 % to 96.04 % mucoadhesion up to 6 hours in simulated intestinal fluid (phosphate buffer, pH 6.8).

Encapsulation of Olive (Olea europaea L.) Pruning Waste Particles by Supercritical CO2 Technology.

Olive leaves (Olea europaea L.) contain a multitude of bioactive compounds such as sterols, carotenes, triterpenic alcohols and phenolic compounds. These compounds have been shown to exhibit antiviral, antioxidant, candida-growth-inhibitory, anticancer, antifungal, anti-inflammatory and antibacterial activities. In this sense, submicron particles from olive leaves with antioxidant activity were precipitated by supercritical antisolvent extraction in a previous work. Moreover, encapsulation enables the delayed release of compounds and avoids the first-step effect in medical therapies. Therefore, this work focused on encapsulation of particles with a certain antioxidant capacity from olive pruning waste using supercritical technology. A variety of experiments were carried out to test how the different operating variables (pressure, temperature and extract-polymer ratio) affect. Morphology was analyzed by SEM microscopy, obtaining encapsulates between 1 and 5 microns in size. The antioxidant capacity was determined by the DPPH assay, with most of the encapsulates having AAI values between 0.5 and 1 (moderate antioxidant capacity). An increase in polyphenol content was observed in the 1:3 ratio tests. The release of the compounds in gastric simulated medium was retarded by the polymeric encapsulation, while in intestinal fluid, the solubility was improved compared to the unencapsulated particles. Overall, the supercritical encapsulation process for the natural extract of olive pruning residues has proven to be effective in obtaining antioxidant particles with different release profiles.

Efficiency of single pharmaceutical surfactants to mimic intestinal biorelevant media solubilization and dissolution of etravirine: Comparison of intrinsic and film dissolution models

We understand that quality control dissolution media may best anticipate in vivo product performance by mimicking in vivo media, but preferably involve at most a single pharmaceutical surfactant for routine laboratory use. The objective here was to estimate the concentrations of six pharmaceutical surfactants to mimic etravirine solubility and intrinsic dissolution rate, as well as dissolution rate from a film model, in each Fed State Simulated Intestinal Fluid Version 2 (FeSSIF-V2) and Fasted State Simulated Intestinal Fluid Version 2 (FaSSIF-V2). Solubility studies and colloid sizing measurements were conducted. Results indicate that all six surfactants were more efficient than FeSSIF-V2 or FaSSIF-V2 at solubilizing drug, and also exhibited higher micelle diffusivities than FeSSIF-V2 and FaSSIF-V2 mixed-micelles. The rank-order potency (on mM basis) of the six pharmaceutical surfactants to mimic etravirine solubility in each FeSSIF-V2 and FaSSIF-V2 was: polysorbate 80 (PS80) > polysorbate 20 (PS20) > polyoxyethylene(23) lauryl ether (POE23) > POE10 > hexadecyltrimethylammonium bromide (HEX) > sodium lauryl sulfate (SLS). This rank-order potency was almost the same to mimic drug dissolution rate into each FeSSIF-V2 and FaSSIF-V2, except POE10 > POE23. For the most potent surfactant, PS80, 0.461 mM and 0.140 mM PS80 was estimated to mimic etravirine's solubility and dissolution rate into FeSSIF-V2, respectively, using the intrinsic dissolution model. The low PS80 concentration to mimic dissolution rate reflects the relatively high diffusivity of PS80 micelles, compared to FeSSIF-V2 mixed-micelle diffusivity, which was the case for all six pharmaceutical surfactants. Results are also presented in terms of a film dissolution model for surfactant-mediated dissolution, where dissolution enhancement was less than that in the intrinsic dissolution model, and the film model required lower surfactant concentration than in intrinsic dissolution model to mimic FeSSIF-V2-enhanced dissolution. Findings have promised to identify single pharmaceutical surfactant concentrations that mimic key performance attributes of biorelevant media.

Sporisorium reilianum polysaccharides improve DSS-induced ulcerative colitis by regulating intestinal barrier function and metabolites

This study investigated the regulatory effects of Sporisorium reilianum polysaccharides (SRPS) on metabolism and the intestinal barrier in mice with colitis induced by dextran sulfate sodium (DSS). SRPS were resistant to the digestion of saliva, gastric juices, and intestinal fluid. SRPS significantly reduced the disease activity index and inhibited DSS-induced colon shortening. The expression of proinflammatory cytokines in the colon was normal (P < 0.05). Acetic acid, propionic acid, butyric acid, isobutyric acid, and isovaleric acid contents increased. Moreover, 64 biomarker metabolites were affected, including 42 abnormal decreases and 22 abnormal increases caused by DSS, which targeted amino acid biosynthesis; tryptophan metabolism; protein digestion and absorption; aminoacyl-tRNA biosynthesis; and glycine, serine, and threonine metabolism. In addition, SRPS reduced goblet cell loss and increased mucin secretion. The short-chain fatty acid receptor GPR41 was activated, and zonula occludens-1 and occludin expression levels were upregulated. Epithelial cell apoptosis was inhibited by increased Bcl-2 and decreased Bax expression NLRP3, ASC, and caspase-1 protein levels decreased. Intestinal barrier damage improved, and colon inflammation was reduced. Thus, our preliminary findings reveal that SRPS regulates metabolism and has the potential to protect the intestinal barrier in ulcerative colitis mice.

Viability of Free and Alginate-Carrageenan Gum Coated Lactobacillus acidophilus and Lacticaseibacillus casei in Functional Cottage Cheese.

The survivability of encapsulated and nonencapsulated probiotics consisting of Lactobacillus acidophilus and Lacticaseibacillus casei and the nutritional, physicochemical, and sensorial features of cottage cheese were investigated under refrigeration storage at 4 °C for 28 days. Microbeads of L. acidophilus and L. casei were developed using 2% sodium alginate, 1.5% sodium alginate and 0.5% carrageenan, and 1% sodium alginate and 1% carrageenan using an encapsulation technique to assess the probiotic viability in cottage cheese under different gastrointestinal conditions (SGF (simulated gastric juice), SIF (simulated intestinal fluid)), and bile salt) and storage conditions. Scanning electron microscopy (SEM) elucidated the stable structure of microbeads, Fourier transform infrared spectroscopy (FTIR) confirmed the presence probiotics in the microcapsules, and X-ray diffraction (XRD) demonstrated the amorphous state of microbeads. Furthermore, the highest encapsulation efficiency was observed for alginate 1% and carrageenan 1% microbeads (T3), i.e., 95%. Likewise, viability was recorded in T3 against SGF, SIF, and bile salt solution, i.e., 8.5, 8.8, and 8.9 log CFU/g at 80 min of exposure, compared to the control. The results of pH showed a significant (p < 0.05) decline that ultimately increased the titratable acidity. Nutritional analysis of cottage cheese revealed the highest levels of ash, protein, and total solids in T3, exhibiting mean values of 3.2, 22, and 43.2 g/100 g, respectively, after 28 days of storage. The sensory evaluation of cottage cheese demonstrated better color, flavor, and textural attributes in T3. Conclusively, synergistic addition of L. acidophilus and L. casei encapsulated with alginate-carrageenan gums was found to be more effective in improving the viability of probiotics in cottage cheese than noncapsulated cells while carrying better magnitudes of ash and protein, lower acidity, and pleasant taste.

Oral Delivery of Astaxanthin via Carboxymethyl Chitosan-Modified Nanoparticles for Ulcerative Colitis Treatment.

The oral delivery strategy of natural anti-oxidant and anti-inflammatory agents has attracted great attention to improve the effectiveness of ulcerative colitis (UC) treatment. Herein, we developed a novel orally deliverable nanoparticle, carboxymethyl chitosan (CMC)-modified astaxanthin (AXT)-loaded nanoparticles (CMC-AXT-NPs), for UC treatment. The CMC-AXT-NPs were evaluated by appearance, morphology, particle size, ζ-potential, and encapsulation efficiency (EE). The results showed that CMC-AXT-NPs were nearly spherical in shape with a particle size of 34.5 nm and ζ-potential of -30.8 mV, and the EE of CMC-AXT-NPs was as high as 95.03%. The CMC-AXT-NPs exhibited preferable storage stability over time and well-controlled drug-release properties in simulated intestinal fluid. Additionally, in vitro studies revealed that CMC-AXT-NPs remarkably inhibited cytotoxicity induced by LPS and demonstrated superior antioxidant and anti-inflammatory abilities in Raw264.7 cells. Furthermore, CMC-AXT-NPs effectively alleviated clinical symptoms of colitis induced by dextran sulfate sodium salt (DSS), including maintaining body weight, inhibiting colon shortening, and reducing fecal bleeding. Importantly, CMC-AXT-NPs suppressed the expression of pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β and ameliorated DSS-induced oxidative damage. Our results demonstrated the potential of CMC-modified nanoparticles as an oral delivery system and suggested these novel AXT nanoparticles could be a promising strategy for UC treatment.

Optimizing the viability of microencapsulated Lactiplantibacillus plantarum using response surface methodology for dietary probiotic delivery

The study aimed to develop a microencapsulated probiotic (Lactiplantibacillus plantarum) delivery method, cryoprotected by chitosan-inulin complex microcapsules and freeze-dried to obtain maximum cell viability. Probiotic viability was assessed using simulated gastrointestinal conditions and storage at different temperatures. The L. plantarum microcapsules were developed using a Box-Behnken experimental design with varied concentrations of CaCl2, chitosan, and Inulin as an encapsulant agents. In addition, the current study used the response surface approach to explore the influence of various formulations and storage capsulate viabilities to verify an optimized L plantarum formulation. Under optimum conditions, small microbeads with the highest cell encapsulation efficiency were produced and the highest cell viability (68.33 %) was obtained. The results showed that the intelligent microcapsule of L. plantarum with SM significantly increased the viability of cells (p < 0.05) (approx. 108 log CFU/mL) and the release of the extract (85 %) in gastric simulation and intestinal simulation fluids, respectively when compared with free bacteria. In general, microencapsulated L. plantarum under previously optimized freeze-drying conditions showed promising efficiency that depends on cell viability during drying, gastrointestinal treatment, and refrigerated storage conditions and on the physicochemical properties of the powders.

Importance of Considering Fed-State Gastrointestinal Physiology in Predicting the Reabsorption of Enterohepatic Circulation of Drugs

PurposeThe purpose of this study was to develop a simulation model for the pharmacokinetics (PK) of drugs undergoing enterohepatic circulation (EHC) with consideration to the environment in the gastrointestinal tract in the fed state in humans. The investigation particularly focused on the necessity of compensating for the permeability rate constant in the reabsorption process in consideration of drug entrapment in bile micelles.MethodsMeloxicam and ezetimibe were used as model drugs. The extent of the entrapment of drugs inside bile micelles was evaluated using the solubility ratio of Fed State Simulated Intestinal Fluid version 2 (FeSSIF-V2) to Fasted State Simulated Intestinal Fluid version 2 (FaSSIF-V2). Prediction accuracy was evaluated using the Mean Absolute Percentage Error (MAPE) value, calculated from the observed and predicted oral PK profiles.ResultsThe solubilization of ezetimibe by bile micelles was clearly observed while that of meloxicam was not. Assuming that only drugs in the free fraction of micelles permeate through the intestinal membrane, PK simulation for ezetimibe was performed in both scenarios with and without compensation by the permeation rate constant. The MAPE value of Zetia® tablet, containing ezetimibe, was lower with compensation than without compensation. By contrast, Mobic® tablet, containing meloxicam, showed a relatively low MAPE value even without compensation.ConclusionFor drugs which undergo EHC and can be solubilized by bile micelles, compensating for the permeation rate constant in the reabsorption process based on the free fraction ratio appears an important factor in increasing the accuracy of PK profile prediction.

The role of calcium bentonite as a delivery carrier for an antihypertensive drug

Clays and clay minerals have been widely used as carriers for drug delivery due to their properties such as cation exchange capacity, adsorption, and biocompatibility. In this study, a new drug release system was obtained by adsorption of amiloride hydrochloride on calcium bentonite (Ca2+-Bent). The ‘in vitro’ release tests were evaluated in the gastric (SGF, pH 1.2), and intestinal (SIF, pH 7.4) simulated fluids. The drug intercalation in clay mineral was confirmed by X-ray diffraction and transmission electronic microscopy, obtaining basal space of 1.59 nm in the hybrid. Zeta potential measurements, infrared spectroscopy, X-ray photoelectron spectroscopy, XRF and calcium release supported the mechanism of drug/clay mineral interaction. The amount of loaded amiloride on Ca2+-Bent was 192.3 mg per gram of solid and characterizations suggested the contribution of both ion exchange and Ca2+ drug complexation in the process. The Ca2+-Bent/amiloride hybrid exhibited a drug-controlled release and reached a release of 53.4% and 38.9% in 11 h in SGF and SIF fluids, respectively. MTT evaluation indicated that system was biocompatible. Ca2+-Bent behaved as a promisor for the drug delivery system.

Microencapsulation of Lactobacillus plantarum with Improved Survivability Using Pufferfish Skin Gelatin-Based Wall Materials.

To improve the survivability of probiotics, Lactobacillus plantarum was microencapsulated using pufferfish skin gelatin (PSG)-based wall materials by spray-drying. This work investigated the protective effect of three different pH-dependent proteins (sodium caseinate (SC), soy protein isolate (SPI), and whey protein isolate (WPI)) combined with PSG on L. plantarum. The experimental results of spray-drying with an inlet temperature of 120 °C and an outlet temperature of 80 °C, storage at 4 °C for 6 months, simulated digestion, and turbidity indicated that PSG/SC had better stability and encapsulation effects and was more suitable to encapsulate L. plantarum than PSG/SPI and PSG/WPI. The optimum preparation conditions for L. plantarum microcapsules were a PSG/SC mass ratio of 2:1, an SC concentration of 20 g/L, and a cell concentration of 10 g/L. The encapsulation efficiency of the obtained microcapsules was 95.0%, and the survival rate was 94.2% in simulated gastric fluid for 2 h and 98.0% in simulated intestinal fluid for 2 h. Amino acid composition analysis exhibited that the imino acid and aspartic acid contents of PSG were 27.98 and 26.16 g/100 g protein, respectively, which was much higher than commercial bovine gelatin. This characteristic was favorable to the high encapsulation efficiency and stability of microcapsules. In vitro release experiments showed that the PSG/SC microcapsules did not disintegrate in simulated gastric fluid for 2 h but could completely release in simulated intestinal fluid for 2 h, which can maintain the high survivability of L. plantarum in simulated digestion. In general, this study demonstrated that microcapsules using PSG/SC as wall materials can effectively improve the survivability of probiotics and have great potential for application in probiotic products.