Search Results (293)

Background: Phytocannabinoids such as cannabidiol (CBD) and cannabigerol (CBG) have received increasing attention in the context of inflammatory and intestinal disorders. However, direct comparisons between their individual and combined effects, as well as the influence of delivery systems, remain limited. Objectives: This study evaluated the biological effects of free and nanoencapsulated CBD and CBG, including a cannabinoid–Eudragit L100 formulation, in an in vitro TNBS-treated intestinal cell model and an in vivo murine model of TNBS-induced colitis. Methods: Cytotoxicity and treatment-associated effects of CBD, CBG, their 1:1 combination, and a nanoencapsulated formulation were assessed in TNBS-exposed Caco-2 cells. In parallel, BALB/c mice with TNBS-induced colitis were evaluated for colonic damage and inflammatory markers. Results: CBD and CBG individually showed dose-dependent effects in Caco-2 cells, while their combined administration produced a greater effect than either compound alone at higher concentrations. The nanoencapsulated formulation preserved cellular metabolic activity following TNBS exposure. In vivo, both free combined and nanoencapsulated cannabinoids were associated with reduced epithelial damage and inflammatory alterations. Conclusions: Nanoencapsulation using Eudragit L100 modulated the biological effects of CBD and CBG in experimental models of TNBS-induced intestinal injury. Full article

Objectives: This study aimed to optimize WS6-loaded nanoparticles (NPs) with favorable therapeutic properties, including appropriate size, low toxicity, high encapsulation efficiency, and enhanced biocompatibility, for selective cancer targeting and regenerative applications. Methods: Three formulations were investigated: solid lipid nanoparticles (SLNs), polycaprolactone (PCL)-based NPs, and Eudragit RS100-based NPs via microfluidic synthesis. Their physicochemical properties were assessed, followed by biological evaluation on normal cells—dental-derived stem cells (DSCs), gingival fibroblasts (GFs), and human dermal fibroblasts (HDFs)—and cancer cell lines MDA-231 and HepG2. Assays included MTT for viability, apoptosis/necrosis, cell cycle analysis, ROS detection, and cytokine profiling. Results: SLNs showed inherent toxicity despite improved viability upon WS6 loading. PCL NPs improved encapsulation and compatibility but lacked stability. The microfluidic RS-WS6 NPs exhibited optimal characteristics, significantly enhancing viability in normal cells and selectively inducing apoptosis in cancer cells. At 1 µM, RS-WS6 NPs reduced ROS in normal cells (p < 0.05) and increased it in cancer cells (p < 0.05). Cytokine analysis revealed significant downregulation of IL-6, IL-12p70, and TNF-α (p < 0.05), indicating immunomodulatory potential. Conclusions: RS-WS6 NPs developed via microfluidics offer a promising therapeutic platform with selective cytotoxicity against cancer cells, minimal toxicity to normal cells, and anti-inflammatory properties, supporting their use in targeted therapy and regenerative medicine. Full article

Background/Objectives: Given the clinical limitations of azathioprine (AZA) in treating inflammatory bowel disease, this study developed an AZA-loaded microbiota-modulating and colon-targeted nanoparticle constructed from pectin, Zein, and Eudragit^®S100 (APZE), which was hypothesized to enhance efficacy while reducing toxicity. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was established to simultaneously quantify AZA and its metabolites, enabling the investigation of the pharmacokinetic and microbial metabolism differences between APZE and AZA suspension (AZAS). Methods: APZE was characterized, and an LC-MS/MS method was developed for quantifying AZA and its metabolites in multiple matrices. Given the potential of APZE for colon targeting and modulation of the microbiota, which may affect drug absorption, distribution, and microbiota-mediated metabolism, we determined analyte concentrations in rat plasma, tissues, and microbial cultures at different time points following administration of APZE or AZAS. Results: AZA, 6-mercaptopurine (6-MP), 6-methylmercaptopurine (6-MMP), and 6-thioguanine (6-TG) were quantified in positive ion mode, and 6-thiouric acid (6-TU) in negative ion mode. The assay demonstrated excellent accuracy, precision, and stability over the concentration range of 5–1000 ng/mL. Orally administered APZE exhibited higher bioavailability, improved intestinal absorption, and reduced formation of the inactive metabolite 6-TU compared to AZAS. In microbial cultures, AZA was metabolized primarily to 6-MP, and APZE underwent more extensive metabolism to 6-MP than AZAS. Conclusions: This method provides accurate and precise quantification of physiologically relevant concentrations of AZA and its metabolites (6-MP, 6-MMP, 6-TG, and 6-TU), offering a bioanalytical tool for the pharmacokinetic and gut microbiota metabolism studies of AZA formulations. These findings suggest that APZE is a promising drug delivery formulation. Full article

Background: Triptolide (TP), a principal bioactive component of Tripterygium wilfordii, exhibits potent anti-inflammatory activity. However, its application is still limited due to its poor solubility and systemic toxicity, primarily caused by uncontrolled absorption after oral administration. Our previously established oral nanomatrix system, composed mainly of commercially available nanoporous Sylysia and Eudragit^®, can not only enhance the in vitro dissolution of poorly water-soluble drugs, but also modulate their absorption sites in gastrointestinal tract. Methods: We prepared a TP nanomatrix system using Sylysia 350 and Eudragit^® L100 to modulate TP’s dissolution in order to overcome TP’s limitation. Then, the nanomatrix was evaluated through in vitro dissolution, physicochemical characterization, and in vivo pharmacokinetic study, and then was comprehensively assessed for efficacy and safety in a rat model of rheumatoid arthritis. Results: TP nanomatrix system exhibited a marked increase in drug dissolution in various media, especially in pH 6.8 medium. The nanomatrix system showed better oral bioavailability than free TP, yet with no toxicity observed. Conclusions: This study developed a simple oral nanomatrix system of TP with enhanced anti-inflammatory efficacy without observed toxicity, and provided a potential strategy to progress the clinical translation of TP products. Full article

Introduction: Diltiazem hydrochloride (DH) is a calcium channel blocker used in the treatment of hypertension, angina pectoris, and arrhythmias. Its short half-life and frequent dosing requirements limit patient adherence and cause plasma concentration fluctuations. Objective: This review critically examines recent pharmaceutical technologies and formulation strategies for modified-release dosage forms (MRDFs) of diltiazem hydrochloride, emphasizing their impact on pharmacokinetics, clinical performance, and regulatory aspects. Methodology: A structured literature review (2010–2025) was conducted using databases such as PubMed, ScienceDirect, MDPI, and ACS Publications. Studies were selected based on relevance to solid oral MRDFs of DH and their associated manufacturing techniques. Results: Techniques including direct compression, granulation, extrusion–spheronization, spray drying, solvent evaporation, and ionotropic gelation have enabled the development of hydrophilic matrices, coated pellets, microspheres, and osmotic systems. Functional polymers such as HPMC, Eudragit^®, and ethylcellulose play a central role in modulating release kinetics and improving bioavailability. Conclusions: This review not only synthesizes current formulation strategies but also explores reverse engineering of ideal release profiles and the integration of advanced modeling tools such as physiologically based pharmacokinetic (PBPK) modeling and in vitro–in vivo correlation (IVIVC). These approaches support the rational design of personalized, regulatory-compliant DH therapies. Full article

Docetaxel (DTX)-loaded polymeric nanoparticles composed of Eudragit RL and RS 100 were developed by solvent evaporation using D-α-tocopheryl polyethene glycol 1000 succinate as an emulsifier and optimised by Central Composite Design. The effects of homogenisation and sonication times on entrapment efficiency (%EE) and drug release (%DR) were statistically analysed across nine batches. Particle size (PS) ranged from 302 ± 1.0 to 502 ± 2.0 nm, and zeta potential (ZP) from 25.8 ± 2.5 to 42.9 ± 1.7 mV. %EE and %DR (pH 1.2 for 2 h, then pH 7.4 for 22 h, 40 mL medium at 37 ± 0.5 °C) ranged from 69.32 ± 3.77 to 92.71 ± 0.16% and 19.24 ± 3.03 to 49.17 ± 1.98%, respectively. Optimised DTX nanoparticles (DNPs) showed EE of 78.18 ± 0.56%, DR of 46.21 ± 1.41% at 24 h, PS of 357.9 ± 2.4 nm, and ZP of 42.9 ± 3.7 mV. Scanning electron microscopy revealed ~300 nm cuboidal particles with smooth surfaces. X-Ray Diffraction and Differential Scanning Colorimetry confirmed reduced drug crystallinity in DNPs. In vitro haemolysis assays showed ~11.5-fold lower haemolytic potential (p < 0.0001) versus DTX, confirming improved safety. Fluorescence microscopy indicated enhanced cellular uptake of DNPs in MDA-MB-231 cells, while cytotoxicity assays of DNPs showed a lower IC₅₀ (39.52 µM) compared to DTX (60.81 µM), demonstrating superior anticancer efficacy. Overall, DNPs represent a promising oral chemotherapy platform for breast cancer management. Full article

Background: Although teriparatide is efficacious, its once-daily subcutaneous injections cause local adverse events, inconvenience, and higher cost, limiting long-term adherence. Therefore, this research aims to engineer a pH-responsive oral formulation of teriparatide for osteoporosis therapy. Methods: A layered silicate nanocomplex was obtained by spontaneous self-assembly of teriparatide (Teri) with 3-aminopropyl magnesium phyllosilicate (AC). The nanocomplex (AC-Teri) was then coated with a 1:1 blend of two polymethacrylic acid derivatives (Eudragit^® L100 and Eudragit^® S 100) to provide pH-triggered drug release along the gastrointestinal tract. Results: AC-Teri and the coated nanocomplex (EE/AC-Teri) displayed high encapsulation efficiency (>90%) with narrow size distributions. In a stepwise buffer transition system, EE/AC-Teri demonstrated pH-dependent release, with less than 25% drug liberated at pH 1.2, approximately 54% at pH 6.8, and 74% at pH 7.4 over 24 h. Particle size and ζ-potential of EE/AC-Teri shifted in parallel with dissolution of the outer polymer shell. EE/AC-Teri also protected the peptide against enzymatic degradation, preserving the secondary structure of encapsulated teriparatide in simulated intestinal fluids. Compared with free drug, EE/AC-Teri enhanced transcellular drug permeation 2.7-fold in Caco-2 cells. In dexamethasone-induced osteoporotic rats, oral EE/AC-Teri significantly stimulated bone formation while suppressing resorption; micro-CT and histology confirmed recovery of trabecular architecture. Conclusions: EE/AC-Teri represents a promising oral teriparatide formulation for the effective management of osteoporosis. Full article

Background/Objectives: Paediatric patients continue to lack access to age-appropriate oral medicines for their treatment and have to depend on the off-label use of medicines approved for adults, which compromises dosing accuracy and exposes children to unpleasant bitterness. Building on previous proof-of-concept work with flucloxacillin sodium, this study investigated the effects of fatty-acid chain length on the formation, stability, dissolution, and sensory acceptability of diclofenac sodium (DS)–Eudragit® EPO (EE)–fatty acid (FA) polyelectrolyte complexes (PECs). Four saturated fatty acids, lauric (C12), myristic (C14), palmitic (C16), and stearic acid (C18), were evaluated at stoichiometric equimolar DS:EE:FA ratio (1:1:1). Methods: PEC microparticles were prepared by solvent evaporation. A stability-indicating RP-HPLC assay was developed and validated according to ICH guidelines to quantify DS content. Drug content and stability were monitored over 3 months at ambient storage. In vitro dissolution was performed in pH 5.5 medium at 37 °C. Taste acceptability and willingness to take again was assessed with 25 healthy adult volunteers using 11-point scale. Results: All PECs retained >90% of expected drug content after 3 months. Compared with neat DS, PECs markedly suppressed early drug release (32–39% vs. 94% at 2 min) but achieved >87% cumulative drug release in 60 min. Sensory evaluation showed significant differences across samples (p < 0.001): neat DS was least acceptable (20.8% willing to take again), while DS-EE-PA was most acceptable (92%), followed by DS-EE-SA and DS-EE-MA. DS-EE-LA was least favoured among PECs. Conclusions: Fatty-acid chain length influenced PEC formation and taste acceptability, but not the PEC stability and drug dissolution profile. Palmitic acid (DS-EE-PA) offered the best overall profile and represents a promising candidate for further development of paediatric-appropriate diclofenac formulations. Full article

Epicatechin is a flavonoid of the catechin subclass, found in fruits and medicinal plants such as açaí and green tea, widely studied for its anti-inflammatory properties. However, flavonoids often present chemical instability, low aqueous solubility, and poor bioavailability, limiting their therapeutic potential. This study aimed to incorporate epicatechin into nanocapsules to improve its applicability and evaluate whether the formulation maintains its anti-inflammatory effects via modulation of the NLRP3 inflammasome. Nanocapsules containing 0.25 mg/mL of epicatechin (NC-ECs) were prepared with Eudragit L-100 using interfacial deposition of a preformed polymer. The formulations were characterized for particle size, polydispersity index, zeta potential, and pH, as well as thermal stability over 45 days. Encapsulation efficiency and drug content were determined by high-performance liquid chromatography (HPLC), and morphology analyzed by atomic force microscopy (AFM). Cytocompatibility was assessed in VERO cells, and anti-inflammatory activity was investigated in THP-1-derived macrophages stimulated with LPS + nigericin. The NC-ECs displayed suitable physicochemical properties, high encapsulation efficiency (96%), and full drug loading. The formulation also showed good cytocompatibility and preserved anti-inflammatory activity through NLRP3 inflammasome modulation at low concentrations. These findings indicate NC-ECs as a promising nanotechnological strategy for treating inflammatory diseases involving NLRP3, highlighting its potential contribution to nanomedicine. Full article

Goji berries (Lycium barbarum L.) are extremely rich in bioactive compounds, including phenolics, flavonoids, and vitamin C, which contribute to the strong antioxidant and immunomodulatory properties, positioning them as a promising candidate for nutraceutical applications. However, due to some limitations such as poor bioavailability and instability, encapsulation via spray drying with polymeric carriers provides a practical strategy to improve their stability, bioavailability, and applicability in the health sector. In this study, goji berry extract (GBE) was obtained via ultrasound-assisted extraction (UAE) and encapsulated using spray drying with four different polymers: alginate, pectin, Eudragit E100 and RS30D. GBE-loaded microparticles showed improved production yields (e.g., 40.3% for Alginate + GBE vs. 13.9% for Alginate alone) and varying particle sizes (1.9–4.4 µm). The antioxidant/antiradical activities were retained to different extents, depending on the carrier, with RS30D + GBE displaying the highest TPC (15.51 mg GAE (gallic acid equivalents)/g), FRAP (59.83 µmol FSE (ferrous sulphate equivalents)/g), and DPPH activities (3.50 mg TE (Trolox equivalents)/g). Biocompatibility was confirmed in HT29-MTX cell lines for all produced microparticles. These findings support the use of spray-dried polymeric carriers to enhance the functional performance and stability of goji berry bioactive compounds in future nutraceutical applications. Full article

Controlling Rhipicephalus microplus is currently one of the main challenges in livestock farming due to the significant economic losses it causes. Traditionally, managing this parasite has been based on the use of synthetic ixodicides, among which fipronil has proven to be highly effective. However, its low water solubility and the limitations of commercially available formulations can affect the bioavailability of this compound, favoring the emergence of resistance in tick populations. In this context, fipronil-loaded nanoparticles were developed using the Eudragit^® E PO polymer (NP_F) (Helm, Naucalpan, Mexico, Mexico), which were physicochemically characterized and evaluated against fipronil-susceptible R. microplus larvae. NP_F had an average size of 143.43 ± 1.88 nm, a polydispersity index (PDI) of 0.162 ± 0.01, a ζ (P ζ) of 21.16 ± 0.54, an encapsulation percentage (%E) of 7.36 ± 0.30, and an encapsulation efficiency percentage (%EE) of 66.28 ± 3.5%. Free fipronil showed an LC₅₀ of 0.582 µg/mL and an LC₉₀ of 2.503 µg/mL against R. microplus. The NP_F formulation showed an LC₅₀ of 0.427 µg/mL and an LC₉₀ of 2.092 µg/mL. These results suggest that incorporating fipronil into nanoparticles improves its ixodicide efficacy, positioning it as an innovative and promising alternative for the development of effective tick control formulations. Full article

Background/Objectives: Lipid-based formulations are widely used to enhance the oral bioavailability of poorly water-soluble drugs. However, for weakly basic drugs with higher solubility under acidic conditions, precipitation and recrystallisation after gastric emptying can compromise a formulation’s ability to maintain the drug in a solubilised, absorbable state. To address this, we evaluated an enteric coating strategy to preserve the biopharmaceutical performance of a silica-solidified lipid-based formulation. Methods and Results: The model weakly basic BCS Class IV drug, abiraterone acetate, was loaded into a lipid-based formulation and solidified using mesoporous silica nanoparticles. In an in vitro lipolysis model, introducing the formulation only after the onset of the intestinal phase led to lower precipitation and over 50% greater drug presence in the aqueous phase compared to a two-stage gastric–intestinal digestion. In an in vivo pharmacokinetic study in Sprague Dawley rats, the silica–lipid formulation (6 mg/kg), delivered in gelatine minicapsules enteric-coated with Eudragit L100-55, resulted in a 2.6-fold higher systemic exposure compared to the non-coated formulation (p < 0.0001). Conclusions: These findings support the use of enteric coating for lipid-based formulations and silica nanoparticles containing weakly basic drugs as a strategy to maintain formulation integrity until reaching the small intestine. Full article

Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was performed. Pseudo-ternary phase diagrams were performed to choose the optimal formulation ratio. The ACM-SEME formulation’s composition was optimized using D-optimal design. Oil, S_mix, and water percentages were used as independent variables, while globule size, polydispersity index, ACM content, and in vitro ACM release after 90 min were used as dependent variables. Also, thermodynamic stability and transmittance percentage tests were studied. Zeta potential was assessed for the optimized ACM-SEME formulation, which was then subjected to spray drying. The dried ACM-SEME was characterized using field-emission scanning electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The dried ACM-SEME formulation was filled into hard gelatin capsules and coated with Eudragit L100 to achieve pH-dependent release. Results: The antinociceptive activity of ACM-SEME was evaluated in vivo using Eddy’s hot plate test in rats, revealing a significant prolongation of the noxious time threshold compared to control groups. Ex vivo permeation studies across rat intestinal tissue confirmed the enhanced permeation potential of the ACM-SEME. Conclusions: It was concluded that the developed ACM-SEME system demonstrated improved physicochemical properties, enhanced release behavior, and superior therapeutic performance, highlighting its potential as a safer and more effective oral delivery platform for ACM. Full article

Additive manufacturing using fused deposition modelling (FDM) is increasingly explored for personalised drug delivery, but the lack of suitable biodegradable and printable filaments limits its pharmaceutical application. In this study, we investigated the influence of formulation and structural design on the performance of polyvinyl alcohol (PVA)-based filaments doped with theophylline anhydrous for 3D printing. To address the intrinsic brittleness and poor printability of PVA, cassava pulp-derived fibres—a sustainable and underutilised agricultural by-product—were incorporated together with polyethylene glycol (PEG 400), Eudragit^® NE 30 D, and calcium stearate. The addition of fibres modified the mechanical properties of PVA filaments through hydrogen bonding, improving flexibility but increasing surface roughness. This drawback was mitigated by Eudragit^® NE 30 D, which enhanced surface smoothness and drug distribution uniformity. The optimised composite formulation (P₁₀F₅E₅T₅) was successfully extruded and used to fabricate 3D-printed constructs. Release studies demonstrated that drug release could be modulated by pore geometry and construct thickness: wider pores enabled rapid Fickian diffusion, while narrower pores and thicker constructs shifted release kinetics toward anomalous transport governed by polymer swelling. These findings demonstrate, for the first time, the potential of cassava fibre as a functional additive in pharmaceutical FDM and provide a rational formulation–structure–performance framework for developing sustainable, geometry-tuneable drug delivery systems. Full article

Objectives: Although 3D-printing has been identified as a promising technique for personalised medicine manufacturing, developing complex formulations that are suitable for the process can be challenging. This study evaluates the use of a mixture design for the targeted development of an optimised formulation designed for the 3D-printing of oral dosage forms containing the drug sertraline hydrochloride featuring immediate-release drug dissolution. Methods: The polymers Eudragit E PO, Kollidon 17 PF and hydroxypropyl cellulose were compared in simple screening experiments regarding their extrudability, printability and disintegration. A combination of Eudragit E PO and Kollidon 17 PF proved superior and therefore served as the basis for the mixture design. The resulting blends were processed via hot melt extrusion to produce filaments, which were then measured for bending stress using a 3-point-bending-test, and 3D-printed sample plates were used to determine the crystallinity index of sertraline hydrochloride using X-ray diffraction in a previously identified range with low interference from the other components. The formulation was optimised using statistically based models with the aim of minimising the bending stress to obtain flexible, process-robust filaments and simultaneously minimising the crystallinity index with the intention of improving the solubility of the drug by maximising its amorphous content. Results: The filaments made from the optimised formulation could be reliably printed, and the amorphous state of the active ingredient therein was confirmed. The oral dosage forms produced from these showed immediate release characteristics in an acidic medium. Conclusions: This study demonstrates the advantages of a mixture design for optimising complex formulations in a time- and resource-efficient way and could serve as a basis for other research groups to develop innovative, customisable drug delivery systems more effectively. Full article