Search Results (304)

Dextrin-based nanosponges (D-NS) are promising candidates for oral drug delivery due to their biocompatibility, mucoadhesive properties, and tunable swelling behavior. In this study, pH-sensitive nanosponges were synthesized using β-cyclodextrin (β-CD), GluciDex^®2 (GLU2), and KLEPTOSE^® Linecaps (LC) as building blocks, crosslinked with pyromellitic dianhydride (PMDA) and citric acid (CA). The nanosponges were mechanically size-reduced via homogenization and ball milling, and characterized by FTIR, TGA, dynamic light scattering (DLS), and zeta potential measurements. Swelling kinetics, cross-linking density (determined using Flory–Rehner theory), rheological behavior, and mucoadhesion were evaluated under simulated gastric and intestinal conditions. The β-CD:PMDA 1:4 NS was selected for drug studies due to its optimal balance of structural stability, swelling capacity (~863% at pH 6.8), and highest apomorphine (APO) loading (8.23%) with 90.58% encapsulation efficiency. All nanosuspensions showed favorable polydispersity index values (0.11–0.30), homogeneous size distribution, and stable zeta potentials, confirming suspension stability. Storage at 4 °C for six months revealed no changes in physicochemical properties or apomorphine (APO) degradation, indicating protection by the nanosponge matrix. D-NS exhibited tunable swelling, pH-responsive behavior, and mucoadhesive properties, with nanoparticle–mucin interactions quantified by the rheological synergism parameter (∆G′ = 53.45, ∆G″ = −36.26 at pH 6.8). In vitro release studies demonstrated slow, sustained release of APO from D-NS in simulated intestinal fluid compared to free drug diffusion, highlighting the potential of D-NS as pH-responsive, mucoadhesive carriers with controlled drug release and defined nanoparticle–mucin interactions. Full article

Biopolymeric films based on chitosan and starch offer an ecological alternative for food protection. Nevertheless, their practical application is often limited by their low mechanical properties and high solubility in aqueous solutions, due to weak interactions between the chains of the biopolymers. One approach to resolve this problem is to obtain biopolymeric films based on (bio)polyelectrolyte complex ((bio)PEC). These films exhibit stronger electrostatic interactions and homogeneous biopolymeric structure. In this study, films based on (bio)PEC were obtained by the casting method, using chitosan and carboxymethyl cassava starch with different degrees of substitution with a biopolymer concentration of 2.5 wt.% at pH = 6. The obtained films were analyzed using the optical and scanning microscopy, color method, ATR-FTIR spectroscopy, thermogravimetry, mechanical analysis under tension, solubility in water, simulated gastric fluid (SGF), and phosphate-buffered saline (PBS) solutions, and contact angle of water. The results demonstrated that the tensile strength and Young’s modulus of films based on (bio)PEC increased by 2–4 times, and the elongation at break by 20% compared to films based on a mixture chitosan and starch. This is due to the increase in the attraction between oppositely charged polyelectrolytes in (bio)PEC films. Additionally, the solubility of (bio)PEC films was reduced by ~40%, 35% and 70% in water, SGF and PBS solutions, respectively, when the carboxymethyl starch with highest degree of substitution was used, and z was near to 1. Full article

Background/Objectives: The ABCG2 transporter actively effluxes anticancer drugs, reducing their efficacy and promoting multidrug resistance (MDR). Developing oral formulations of poorly soluble ABCG2 inhibitors remains challenging due to their low solubility and intestinal permeability. This study aimed to formulate and evaluate an ABCG2 inhibitor using micro- and nanoscale drug delivery systems. Methods: To address the poor solubility and bioavailability of the corresponding active ingredient, a self-nanoemulsifying drug delivery system (SNEDDS) was developed. The SNEDDS was encapsulated into microcapsules using sodium alginate crosslinked with calcium chloride. Five microcapsule formulations were developed, varying in the inclusion of polyvinylpyrrolidone (PVP), Transcutol^® HP and SNEDDS. The effects of the excipients on encapsulation efficiency, swelling capacity, enzymatic stability, dissolution, cytocompatibility, and permeability were systematically evaluated. Results: The SNEDDS exhibited monodisperse particle sizes and efficient drug entrapment. Results revealed that formulations incorporating PVP and SNEDDS improved encapsulation efficiency and bioavailability. SNEDDS-containing formulations demonstrated superior enzymatic stability in simulated gastric and intestinal fluids and provided the highest cumulative drug release in vitro. Cytotoxicity studies conducted on Caco-2 and MCF-7 cells demonstrated that our formulations were well tolerated, indicating favorable biocompatibility. Conclusions: Our findings demonstrate that SNEDDS-loaded alginate microcapsules offer an efficient platform for oral delivery of dimeric ABCG2 inhibitors, combining enhanced solubility, stability, and controlled release. The optimized formulation can be regarded as a promising strategy to enhance the oral bioavailability of efflux pump inhibitors and other poorly soluble drugs. Full article

Background/Objectives: Prussian blue (PB) is the agent of choice for internal cesium (Cs) decorporation, yet its performance is critically dependent on gastrointestinal (GI) pH and formulation attributes. Hypochlorhydria, common in patients treated with proton pump inhibitors, may alter the stagewise distribution of Cs binding during GI transit. This study aimed to compare the performance of different PB formulations in sequential in vitro models simulating normogastria and hypochlorhydria: normogastric regimen (NG) and hypochlorhydric regimen (HC). Methods: A static, enzyme-free sequential model was applied using compendial simulated fluids (SGFs pH 1.2 or acetate pH 4.0, SIF pH 6.8, and phosphate buffer pH 7.2). The formulations tested included PB active pharmaceutical ingredient (API) (bulk), compression blend, PB tablets 500 mg (PB tablets), and Radiogardase^®. For each stage, cesium bound (qs, mg/g PB), fractional contributions (fs), and total capture (qtotal) were quantified. Additional analyses included sensitivity to initial Cs concentration (C₀) and desorption in mineralized water. Results: Overall performance was primarily determined by formulation (p < 0.0001), with a significant formulation × regimen interaction. The compression blend and PB tablets exhibited the highest decorporation capacity, PB-API showed intermediate performance, and Radiogardase^® was clearly lower. Under HC, capture was concentrated in the gastric stage (44–47%), whereas in NG, it shifted toward intestinal stages. Desorption in the mineralized water was statistically significant but negligible compared with total capture, supporting the stability of cesium sequestration. Conclusions: Formulation and gastric acidity regimens not only determine the total cesium capture but also redistribute it across the GI tract. PB tablets represent an effective and accessible alternative to Radiogardase^®, maintaining robust decorporation capacity under clinically relevant pH conditions. Full article

Background: Epigallocatechin-3-gallate (EGCG), a potent green tea polyphenol, possesses significant therapeutic potential, but its clinical application is limited by poor gastrointestinal stability and low oral bioavailability. To address this, a novel herbal nanomedicine-based delivery system was developed utilizing D-α-tocopheryl polyethylene glycol succinate (TPGS) and Poloxamer 407. Objectives: This study aims to develop and characterize EGCG-loaded TPGS/Poloxamer 407 micelles, evaluating their physicochemical properties, storage stability, in vitro drug release profile, in vivo oral bioavailability, and preliminary tolerability observation. Methods: The micelles were prepared using the film hydration method followed by lyophilization. Results: The optimized 2:2 TPGS-to-poloxamer 407 weight ratio yielded EGCG-loaded micelles, displaying a mean particle size of 15.4 nm, a polydispersity index (PDI) of 0.16, a zeta potential of −17.7 mV, an encapsulation efficiency of 82.7%, and a drug loading capacity of 7.6%. The critical micelle concentration (CMC) was determined to be 0.00125% w/v. Transmission electron microscopy (TEM) confirmed the micelles’ uniform spherical morphology. In vitro release studies demonstrated a sustained release profile in both simulated gastric and intestinal fluids. EGCG formulation remained stable for at least six months when stored at 4 °C. No adverse clinical signs were noted during the 28-day tolerability observation. In vivo pharmacokinetic evaluation in mice revealed a significant elevation in oral bioavailability, achieving a 2.27-fold increase in area under the curve (AUC) and a 1.8-fold increase in peak plasma concentration (Cmax) compared to free EGCG. Conclusions: Collectively, these findings underscore the potential of the TPGS/poloxamer 407-based micelle system as a promising oral delivery platform for EGCG, enhancing its stability and pharmacokinetic performance. Full article

Gelatin microparticles (GMPs) can load functional active substances, but they tend to redissolve in high-temperature aqueous solutions during food processing. In this study, a new loading system adapted to food processing and digestive environments was constructed through the crosslinking of tea polyphenols (TP) on GMPs. The effects of pH, temperature, and crosslinking time on the methylene blue (MB) retention rate in crosslinked gelatin microparticles (cGMPs) were investigated, resulting in optimized crosslinking conditions. Compared with GMPs, the surface of cGMPs was denser and smoother. ATR-FTIR results showed that the N–H groups were involved in the formation of hydrogen bonds during the crosslinking process. The crosslinking effect of TP significantly disrupted the triple-helical structure of gelatin. The melting temperature ($T_m$) of cGMPs is 147.79 °C, which is significantly higher than that of GMPs (87.11 °C), indicating a marked improvement in thermal stability. In high-temperature aqueous solutions, Folic acid-loaded cGMPs (FA-cGMPs) maintained morphological integrity for 2 h (at 40 °C) and 0.5 h (at 60 °C). In vitro digestion simulations revealed excellent sustained-release characteristics of FA-cGMPs, with a release rate of only 4.91% in simulated gastric fluid and 88.13% in simulated intestinal fluid. This study provides an ideal carrier with food processing stability and intestinal-targeted release capabilities for functional active substances. Full article

Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide and an endocannabinoid-related lipid that has been extensively studied for its analgesic, immunomodulatory, antimicrobial, and anti-inflammatory properties. It has demonstrated efficacy in various applications and is currently utilized as a nutraceutical for its antinociceptive, neuroprotective, and immunomodulatory effects, particularly in supporting brain and joint health and in mitigating inflammatory processes. Background/Objectives: Despite its significant therapeutic potential, the clinical effectiveness of PEA is limited by its poor water solubility and, consequently, low oral bioavailability. Additionally, degradation in the acidic gastrointestinal environment further compromises its absorption. To address these challenges, several technological strategies have been explored to improve its pharmacokinetic profile, including conventional micronization and ultra-micronization techniques. The objective of this study was to characterize a novel liposomal formulation based on PEA and evaluate its intestinal permeation and absorption. Methods: Comparative permeation studies of PEA were conducted using ex vivo models to evaluate its absorption characteristics across gastrointestinal mucosae. The experiments were performed in a Franz diffusion cell system using a porcine colon mucosa in two physiologically relevant media: Simulated Gastric Fluid (SGF) and Fasted State Simulated Intestinal Fluid (FaSSIF). Results: Liposomal PEA showed a more efficient and continuous release over time, reaching higher concentrations of PEA permeated through the membrane. Conclusions: Our findings demonstrate a significant improvement in PEA’s permeability and absorption in an ex vivo simulated gastrointestinal environment. Liposomal PEA appears to be more affine to biological membranes. These results suggest that liposomal PEA may represent a promising therapeutic strategy for managing chronic pain and inflammatory conditions such as chronic pelvic pain. Full article

Radiation-induced intestinal injury (RIII), a severe complication of abdominopelvic radiotherapy, causes intestinal ischemia, ulcers, and necrosis, severely impacting patients’ quality of life. Currently, effective treatments are limited, and a specific cure remains elusive. Our previous research showed that lactoferrin (LF) can promote intestinal stem cell (ISC) proliferation and tissue repair; however, its oral administration is limited by rapid degradation in the gastric environment. In this study, we developed LF-loaded liposomal nanoparticles (Lip-LF) using a simple ethanol injection method. The optimal formulation (cholesterol/egg yolk lecithin ratio 2:8, LF concentration 12.5 mg/mL) achieved a drug-loading capacity of 6.8% and a narrow size distribution (0.2 < PDI < 0.4). In vitro experiments demonstrated that Lip-LF protected LF from pepsin degradation in simulated gastric fluid (SGF), retaining over 80% integrity after 120 min, while releasing in simulated intestinal fluid (SIF). In vivo imaging revealed prolonged gastrointestinal retention of Lip-LF compared to free LF. In a murine model of RIII (12 Gy whole-body irradiation), Lip-LF significantly restored villus counts, increased crypt height, and promoted goblet-cell regeneration. Immunohistochemical and qPCR analyses revealed enhanced ISCs proliferation and upregulation of repair-associated genes, including Pcna and Olfm4. These findings demonstrate that Lip-LF protects LF from gastric degradation and enhances its targeted delivery to the intestine, improving its therapeutic efficacy in repairing RIII. Lip-LF thus offers a promising strategy for managing RIII. Full article

Encapsulation of fish oil within oleogels can potentially prevent oxidation and enable its use in food with programmable release within the gastrointestinal tract. Here, we report on the formation of oleogels from two different fish oils—salmon oil (SO) and cod liver oil (CLO)—using different concentrations of either rice bran wax (RBW) or myristic acid (MA) as gelators. The gels were assessed with respect to their structural, thermal, viscosity, digestive, and oxidative properties. Polarized light microscopy (POM) revealed that RBW consistently produced dense, interconnected crystalline networks across both oils, while MA formed larger, spherulitic crystals that were more sensitive to the oil type. This was further supported by time-lapse imaging, showing faster crystal growth of MA in cod liver oil. Viscosity studies indicate that the molecular weight and concentration of gelator, as well as the type of fish oil (SO vs. CLO), significantly impact the shear stability of the oleogels. Thermal and viscosity analyses confirmed that RBW-based oleogels exhibited higher crystallization temperatures and stronger viscoelastic behaviour. Based on oxidative stability measurements—as measured by peroxide value (PV) analysis—encapsulation within oleogels does not lead to significant oxidation of the fish oils and also attenuates further oxidation upon storage. The fish oil oleogels were stable when exposed to either simulated gastric or intestinal fluids (SGF and SIF, respectively), but decomposed after sequential exposure first to SGF and then to SIF. These findings could broaden the range of food products which can be fortified with fish oils. Full article

The global challenge of food waste presents an opportunity to explore the untapped potential of agricultural by-products. Coffee pulp, a major by-product of the coffee industry, is a promising source of functional polysaccharides such as coffee pectin, which can be valorized for sustainable applications in food systems. This study investigates the microencapsulation of hemp seed oil—rich in essential fatty acids and bioactive lipids—using coffee pectin and maltodextrin as wall materials via spray drying. Emulsions with varying oil-to-wall ratios were formulated and characterized for viscosity, particle size, and zeta potential. The resultant microcapsules were analyzed for physicochemical properties, encapsulation efficiency, oxidative stability (peroxide value), and in vitro release in simulated gastrointestinal fluids. Encapsulation efficiencies ranged from 63.27% to 70.77%, with lower oil content formulations exhibiting higher efficiency. The peroxide values indicated enhanced oxidative stability, with the lowest value (10.69 meq O₂/kg oil) observed in the most efficient encapsulation formulation. Microcapsule morphology analysis confirmed the formation of spherical particles with varying degrees of surface roughness. Release studies demonstrated controlled oil delivery, with higher retention in gastric conditions and progressive release in intestinal fluids. These findings demonstrate the potential of upcycled coffee pulp-derived pectin as a functional, sustainable encapsulant, aligning with circular economy principles and supporting the development of stable bioactive delivery systems for nutraceutical and food applications. Full article

Probiotics are microorganisms with recognized beneficial properties that are used to improve host health. In particular, probiotics administered as spores, such as those belonging to the genera Bacillus and Alkalihalobacillus, are attracting great interest due to their high tolerance to gastrointestinal conditions. This in vitro study aimed to assess the probiotic attributes potentially contributing to the in vivo beneficial effects of a commercial spore-based probiotic formulation composed of four Alkalihalobacillus clausii strains. The tolerance and survival of the spores from the formulation in simulated gastrointestinal fluids, as well as their germination rate and adhesion to mucins, were analyzed. Furthermore, metabolic properties of spore-derived vegetative cells were assessed, including lactose degradation and biosynthesis of antioxidant enzymes (catalase and superoxide dismutase), group B vitamins (B₂, B₈, B₉, and B₁₂), short-chain fatty acids (acetate, propionate, and butyrate), and D-lactate. A. clausii spores were shown to survive in artificial gastric juice, adhere to mucins and germinate in vitro, and replicate in simulated intestinal fluid, suggesting their potential resilience in the gastrointestinal tract, where they can exert beneficial effects after germination. A. clausii was also able to produce beneficial enzymes and metabolites, including β-galactosidase, catalase, superoxide dismutase, group B vitamins, and short-chain fatty acids, but it was unable to produce D-lactic acid. Our findings highlight the probiotic properties and potential of such A. clausii strains in both their spore and vegetative forms, reinforcing the clinical relevance of this multi-strain spore-based formulation for enhancing intestinal health. Full article

Calcium phosphate (CaP) materials are biocompatible and non-toxic to the body. However, they lack biointegration, exhibit a low resorption rate and can cause fibrous encapsulation throughout the implant material. A promising approach for dental or orthopedic regeneration is the use of dicalcium phosphate dihydrate (DCPD) and octacalcium phosphate (OCP), as they are well-suited to bone components. From a novel perspective, these apatites can be used as drug carriers for individuals with low tolerance to common excipients. In this study, the transformation of DCPD into different morphologies in DMEM was investigated using an induced dissolution and reprecipitation reaction solution. The DCPD transformation time was observed to be morphology-dependent and can occur between 48 and 168 h. In the interaction with simulated body fluid (SBF), simulated gastric fluid (SGF) and a combination of both (BFS/SGF), a higher mass loss was observed in SGF (~80%) than in the other fluids (~35%). The structural changes presented in DCPD and OCP before and after immersion in physiological fluids were analyzed by ATR-FTIR, SEM, XRD and EDS. The obtained OCP showed low stability in SGF compared to SBF and SBF/SGF, which indicates that it may be a suitable candidate for drug delivery in the digestive tract. Full article

Background/Objectives: Oral delivery of biologics offers advantages for patient access and adherence compared to injection, but suffers from low bioavailability due to mucosal barriers and drug degradation in the gastrointestinal tract. We previously developed an oral self-pressurized aerosol (OSPRAE) capsule that uses effervescent excipients to generate CO₂ gas, building internal pressure to eject powdered drug at high velocity across intestinal mucosa. Methods: Here, we developed two key design improvements: (i) an enteric covering to protect the capsule delivery orifice in gastric fluids and (ii) reduced humidity content of capsules to extend shelf-life. Results: Enteric-covered capsules prevented drug release in simulated gastric fluid and then enabled rapid release upon transfer to simulated intestinal fluid. Burst pressure for enteric-covered capsules was ~3–4 times higher than non-covered capsules. After storage for up to three days, the capsules’ effervescent excipients pre-reacted, making them unable to achieve high pressure during subsequent use. To address this limitation, we prepared capsules under reduced humidity conditions, which inhibited pre-reaction of effervescent excipients during storage, and a polyurethane coating to improve water uptake into the capsule to drive the effervescence reaction in intestinal fluid. Conclusions: These design improvements enable improved functionality of OSPRAE capsules for continued translation in pre-clinical and future clinical development. Full article

The present study develops and optimizes a jet-cutting encapsulation method using a laboratory-scale encapsulator to incorporate herbal dietary supplements into fermented milk products. Sodium alginate and pullulan were selected as core and coating polymers, respectively, after rheological screening demonstrated that 1% alginate (η ≈ 350–450 Pa·s at 22–25 °C) and 2% pullulan (η ≈ 400 Pa·s at 25–30 °C) provide a balance between atomization, shell integrity, and fluidity. Under optimized conditions, capsules of 1.00 ± 0.05 mm diameter and high sphericity (aspect ratio 1.08 ± 0.03) were produced. In vitro gastrointestinal simulation confirmed capsule stability in simulated gastric fluid (pH 2.0) and complete disintegration within 120 min in simulated intestinal fluid (pH 7.2). Inclusion of 8% (w/w) capsules in a fermented milk beverage preserved appearance, texture, flavor, and color while increasing viscosity from 2.0 to 4.0 Pa·s. Titratable acidity rose from 87 °T at 24 h to 119 °T at 120 h, with sensory quality remaining acceptable; substantial gas formation and excessive sourness occurred only after 168 h, defining a 5-day refrigerated shelf life. These findings demonstrate that the 1% alginate–pullulan capsule system successfully protects plant extracts during gastric transit and enables targeted intestinal release, while maintaining the sensory and rheological properties of the fortified fermented milk product. Full article

The growing interest in probiotic bacteria within the food industry is driven by their recognized health benefits for consumers. However, preserving their therapeutic viability and stability during gastrointestinal transit remains a formidable challenge. Hence, this research aimed to enhance the viability of Lactobacillus reuteri through microencapsulation using a binary polysaccharide mixture composed of low acyl gellan gum (LAG), high acyl gellan gum (HAG), and calcium for the microencapsulation of L. reuteri. To achieve this, the Box–Behnken design was applied, targeting the optimization of L. reuteri microencapsulated to withstand simulated gastrointestinal conditions. The microcapsules were crafted using the internal ionic gelation method, and optimization was performed using response surface methodology (RSM) based on the Box–Behnken design. The model demonstrated robust predictive power, with R² values exceeding 95% and a lack of fit greater than p > 0.05. Under optimized conditions—0.88% (w/v) LAG, 0.43% (w/v) HAG, and 24.44 mM Ca—L. reuteri reached a viability of 97.43% following the encapsulation process. After 4 h of exposure to simulated gastric fluid (SGF) and intestinal fluid (SIF), the encapsulated cells maintained a viable count of 8.02 log CFU/mL. These promising results underscore the potential of biopolymer-based microcapsules, such as those containing LAG and HAG, as an innovative approach for safeguarding probiotics during gastrointestinal passage, paving the way for new probiotic-enriched food products. Full article