Search Results (99)

Lipid nanoparticle (LNP)-based delivery systems are promising tools for advancing RNA-based therapies. However, there are underlying challenges for the oral delivery of LNPs. In this study, we optimized an LNP formulation, which we encapsulated in a pH-sensitive Eudragit^® S 100 (Eu) coating. LNPs were prepared using the DLin-MC3-DMA ionizable lipid, cholesterol, DMG-PEG, and DSPC at a molar ratio of 50:38.5:10:1.5. LNPs were coated with 1% Eu solution via nanoprecipitation using 0.25% acetic acid to get Eu-coated LNPs (Eu-LNPs). Particle characteristics of LNPs were determined by using dynamic light scattering (DLS). Ribogreen and agarose gel retardation assays were used to evaluate nucleic acid entrapment and stability. LNPs and Eu-LNPs were ~120 nm and 4.5 μm in size, respectively. Eu-LNPs decrease to an average size of ~191 ± 22.9 nm at a pH of 8. Phosphate buffer (PB)-treated and untreated Eu-LNPs and uncoated LNPs were transfected in HEK-293 cells. PB-treated Eu-LNPs showed significant transfection capability compared to their non-PB-treated counterparts. Eu-LNPs protected their nucleic acid payloads in the presence of a simulated gastric fluid (SGF) with pepsin and maintained transfection capacity following SGF or simulated intestinal fluid. Hence, Eu coating is a potentially promising approach for the oral administration of LNPs. Full article

Background/Objectives: The formulation of microspheres for lipophilic drugs using aqueous methods, such as spray drying, faces significant challenges. The main objective of this study was to evaluate the effect of the process parameters and polymer selection on the production of microspheres by spray drying for a lipophilic drug. Methods: Lipophilic drug-loaded microspheres were developed using various polymers via the aqueous spray drying method. The effects of the factors on the yield percentage and encapsulation efficiency were analyzed. Microspheres preparation included Agave inulin, guar gum, hydroxypropyl methylcellulose, and Eudragit^® S100. A 2³ factorial design was performed, and the parameters were optimized. Results: Inlet temperature, feed flow, and polymer percentage showed a significant effect (p < 0.05) on the yield percentage of guar gum microspheres and encapsulation efficiency of the inulin microspheres. Inulin and guar gum microspheres showed the best yield percentage (75.41%) and encapsulation efficiency (100%), respectively. In addition, guar gum microspheres had the best morphology, and hydroxypropyl methylcellulose microspheres were smaller and had an irregular surface. Eudragit did not maintain its delayed release property due to limitations of the aqueous method; inulin released the drug immediately, and guar gum and hydroxypropyl methylcellulose microspheres prolonged release only by a few additional hours. Conclusions: The experimental design showed that optimizing the parameters (inlet temperature, feed flow, and the type and percentage of polymer) can regulate the microsphere development process to obtain improved product yield and encapsulation efficiency results. Full article

Ulcerative colitis (UC) is a multifactorial disorder, and conventional oral berberine (BBR) suffers from poor colonic targeting. This study aimed to develop a colon-targeted microparticle system (BBR-ES MPs) based on chitosan (CS) and Eudragit S-100 to enhance BBR delivery efficiency and therapeutic efficacy in UC. Methods: BBR-CS nanocarriers were prepared via ionotropic gelation and coated with Eudragit S-100 to form pH/enzyme dual-responsive MPs. Colon-targeting performance was validated through in vitro release assays. SPF-grade male KM mice (Ethics Approval No.: JMSU-2021090301) with dextran sulfate sodium (DSS)-induced UC were divided into normal, model, BBR, and BBR-ES MPs groups. Therapeutic outcomes were evaluated by monitoring body weight, disease activity index (DAI), colon length, histopathology, inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-10), and myeloperoxidase (MPO) activity via ELISA. Gut microbiota diversity was analyzed using 16S rRNA sequencing. Results: BBR-ES MP treatment significantly reduced DAI scores (p < 0.01), restored colon length, downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α; p < 0.05), and upregulated anti-inflammatory IL-10. Microbiota analysis revealed that the Bacteroidetes/Firmicutes ratio, which decreased in the model group, was restored post-treatment, with alpha/beta diversity approaching normal levels. BBR-ES MPs outperformed free BBR at equivalent doses. Conclusion: BBR-ES MPs achieved colon-targeted drug delivery via pH/enzyme dual-responsive mechanisms, effectively alleviating UC inflammation and modulating gut dysbiosis, offering a safe and precise therapeutic strategy for UC management. Full article

Background/Objectives: Triamcinolone acetonide (TA), a poorly water-soluble corticosteroid, presents formulation challenges due to limited membrane permeability. This study aimed to identify suitable drug–polymer–plasticizer systems for TA using combined theoretical and experimental methods. Methods: Using Hansen solubility parameters, seven hot-melt extrusion (HME)-grade polymers and four plasticizers were initially screened for miscibility with TA. Based on Δδt values, four polymers—Eudragit^® L100 (EUD), Parteck^® MXP (PVA), Plasdone^® S-630 (PVPVA), and Aquasolve™ AS-MG (HPMCAS)—along with triethyl citrate (TEC), were selected for experimental evaluation. Differential scanning calorimetry, thermogravimetric analysis, and Fourier transform infrared spectroscopy assessed thermal behavior, miscibility, and chemical compatibility. Results: Amorphous TA content was highest with EUD (81.1%), followed by PVA (67.5%), PVPVA (45.6%), and HPMCAS (8.5%). Thermal incompatibility and TEC evaporation were observed in PVA, PVPVA, and HPMCAS systems. FTIR suggested TEC should be avoided in melt-based formulations with PVA and PVPVA due to PVA degradation and partial TA oxidation. No significant interactions were detected in HPMCAS samples heated to 220 °C, aligning with theoretical predictions. In contrast, the EUD–TEC system showed limited chemical reactivity and maintained TA’s structural integrity. Infrared bands at 1758 and 1802 cm⁻¹ indicated minor anhydride formation above 160 °C with partial TEC evaporation. Conclusions: EUD/TEC were identified as a promising combination for the HME processing of TA. This work supports the rational formulation of stable amorphous systems for thermolabile drugs with poor solubility. Full article

Objectives: Tacrolimus, a Biopharmaceutics Classification System (BCS) class II drug, is widely used for transplant patients to prevent graft rejection. To enhance its bioavailability, amorphous solid dispersion (ASD) formulations were developed and evaluated. The release properties of several ASD-based tacrolimus formulations were studied using an in-house USP IV dissolution method. Methods: The pharmacokinetics of a promising test product were compared with the commercially available Advagraf^® in a pilot clinical bioequivalence study with 12 healthy subjects. A previously published PBPK model for tacrolimus was validated using in vivo data and then applied to predict the human pharmacokinetics of several ASD-based tacrolimus formulations. Results: This study compares the pharmacokinetic (PK) parameters—AUC, Cmax, and Tmax—of Advagraf^® and a test formulation using two methodologies: one incorporating the dissolution profile directly into the PBPK model and the other utilizing the DLM approach. The results show that both methods provided accurate predictions for Cmax and Tmax, with the dissolution profile approach underestimating AUC slightly, while the DLM method predicted AUC adequately. Sensitivity analysis refining the DLM scalars in the Ileum and Colon led to optimized predictions of PK parameters. Furthermore, this study explores the use of PBPK modeling to predict in vivo behavior for additional tacrolimus formulations, highlighting the influence of formulation composition, such as the inclusion of Eudragit-S100, on dissolution profiles and bioavailability. Conclusions: This study evaluates formulations with different compositions and manufacturing characteristics; key factors that could influence their performance in the body were identified. These insights—spanning qualitative, quantitative, and manufacturing aspects—can greatly simplify the development of generic drugs, offering strong evidence of the critical role that physiologically based pharmacokinetic (PBPK) modeling can play in the early phases of generic drug development, especially in designing and assessing biopredictive dissolution methods. Full article

Background/objectives: The aim of the study was to create a nanofiber insert incorporating Timolol (TIM) and Dorzolamide (DOR), targeting the management of glaucoma. This condition encompasses a variety of chronic, advancing ocular disorders typically associated with elevated intraocular pressure (IOP). Methods: The insert was made of Eudragite RL100 (EUD) polymer, a biocompatible material with high bioavailability, using the electrospinning method. The inserts were studied for morphology, drug–polymer interaction, physicochemical properties, and in vitro drug-release study. The pharmacokinetic properties of fibers were examined alongside consideration for irritation using a rabbit model and cell compatibility. Results: The results of the in vitro drug-release test showed retention and controlled release of both DOR/TIM over 80 h. Morphological examination demonstrated uniform nanofibers with mean diameters < 465 nm. The cell compatibility test showed a high percentage of cell survival, and none of the formulations irritated the rabbit’s eye. The Area Under the Curve (AUC0-72) for DOR and TIM in EDT formulations was approximately 3216.63 ± 63.25 µg·h/mL and 2598.89 ± 46.65 µg·h/mL, respectively, with Mean Residence Times (MRTs) of approximately 21.6 ± 0.19 h and 16.29 ± 6.44 h. Conclusions: Based on the results, the dual drug-loaded nanofiber preservative-free system can potentially be a suitable alternative to eye drops and can be used to reduce fluctuation and dose frequency. Full article

Background/Objectives: The objective of this paper is to design a novel film-forming system (FFS) based on Eudragit^® E PO (EuE) polymeric solutions, differing in volatile solvents (i.e., isopropanol and ethanol) and plasticizers (i.e., tributylcitrate, glycerine, triacetin and PEG 400). Methods: The physicochemical and mechanical properties of the FFS and dried films were evaluated in terms of formation time, stickiness, T_g, tensile strength, break elongation and Young’s modulus. The in vitro skin permeation studies were conducted on formulations containing caffeine and testosterone. Results: The FFS, consisting of EuE and PEG400 in isopropyl alcohol and ethanol (80:20, v/v), exhibited rapid film formation within about 5 min and the dried film allowed a high skin permeability compared to other formulations due to the ability to increase the thermodynamic activity of both drugs. When triiodothyronine (T3) was loaded as a model of a very low soluble drug, tocopherol polyethylene glycol succinate (TPGS) was added as a co-solvent and it allowed for the improvement of T3 retention in the skin. Conclusions: Among the formulative variables, the nature and the amount of plasticizer represent the most critical variables to obtain an EuE-based film with satisfying physical and biopharmaceutical properties. Full article

This study’s integration of molecular dynamics (MD) simulations with non-covalent adaptable networks (NANs) and corroborative wet lab experiments offers a comprehensive approach to understanding the interactions between ritonavir (RTV) and polymers in supersaturated solutions. This multifaceted study not only explored the stabilization mechanisms facilitated by NANs but also examined the influence of polymer selection on the pharmaceutical properties of RTV, a class III compound known for its slow crystallization rate. This research utilized molecular dynamics simulations to model the intermolecular interactions between RTV and two polymers, Polyvinylpyrrolidone (PVP) K30 and Eudragit L100. These simulations were specifically designed to incorporate the effects of NANs, highlighting their dynamic nature and potential to enhance drug stability and solubility. Simultaneously, wet lab experiments were conducted to measure the nucleation induction times and observe the crystallization behavior of RTV under varying conditions of polymer presence. The experimental data demonstrated a significant extension in nucleation induction time, prolonging the duration from 12 to approximately 64 h when PVP K30 and Eudragit L100 were present. This substantial delay in crystallization was attributed to the strong intermolecular interactions between RTV and the polymers, which were effectively stabilized by the non-covalent bonds within the NANs. These findings were consistently confirmed across both computational and experimental settings, illustrating how NANs can effectively inhibit crystallization and enhance the supersaturation state of RTV. This study successfully demonstrates how the physical and chemical properties of polymers influence the crystallization process of poorly water-soluble drugs such as RTV. Leveraging the synergy between computational simulations and empirical laboratory data, this research provides deep insights into the mechanisms at play, ensuring that drug formulations are optimized for both stability and performance. Full article

Background/Objectives: Drug–polymer interactions and miscibility promote the formation and performance of amorphous solid dispersions (ASDs) of poorly soluble drugs for improved oral bioavailability. The objective of this study was to employ drug–polymer interaction calculations and small-scale experimental characterization to screen polymers for potential ASDs of ritonavir. Methods: Seven polymers across four polymer types were screened as follows: an enteric one (EudragitS100), amphiphilic ones (HPMCAS-L, HPMCAS-H, and their 1:1 combination), hydrophilic ones (PEG-6000, PVP-VA), and a surfactant (Soluplus), including PVP-VA as a positive control, as the commercial ASD employs PVP-VA. Drug–polymer interaction calculations were performed for Hansen solubility parameter, Flory–Huggins parameter, and glass transition temperature. ASDs were prepared via film casting. Experimental characterizations included drug solubility in polymer solutions, polymer inhibition of drug precipitation, polarized light microscopy, differential scanning calorimetry, solubilization capacity, and dissolution studies. Results: HPMCAS-L, HPMCAS L:H, and Soluplus, along with the positive control PVP-VA, were identified as polymers for potential ASDs of ritonavir, with HPMCAS-L and PVP-VA being preferable. HPMCAS-L and the positive control PVP-VA were always viable for both 20% and 40% drug loads across all tests. Films with each of these four polymers showed improved dissolution compared to amorphous ritonavir without polymer. Drug–polymer interaction calculations anticipated the unfavorable small-scale experimental results for PEG-6000 and EudragitS100. Conclusion: Overall, the results contribute towards a resource-sparing approach to identify polymers for ASDs. Full article

Using free microorganisms for industrial processes has some limitations, such as the extensive consumption of substrates for growth, significant sensitivity to the microenvironment, and the necessity of separation from the product and, therefore, the cyclic process. It is widely acknowledged that confining or immobilizing cells in a matrix or support structure enhances enzyme stability, facilitates recycling, enhances rheological resilience, lowers bioprocess costs, and serves as a fundamental prerequisite for large-scale applications. This report summarizes the various cell immobilization methods, including several synthetic (polyvinylalcohol, polyethylenimine, polyacrylates, and Eudragit) and natural (gelatin, chitosan, alginate, cellulose, agar–agar, carboxymethylcellulose, and other polysaccharides) polymeric materials in the form of thin films, hydrogels, and cryogels. Advancements in the production of well-known antibiotics like penicillin and cephalosporin by various strains were discussed. Additionally, we highlighted cutting-edge research related to strain producers of peptide-based antibiotics (polymyxin B, Subtilin, Tyrothricin, varigomycin, gramicidin S, friulimicin, and bacteriocin), glusoseamines, and polyene derivatives. Crosslinking agents, especially covalent linkers, significantly affect the activity and stability of biocatalysts (penicillin G acylase, penicillinase, deacetoxycephalosporinase, L-asparaginase, β-glucosidase, Xylanase, and urease). The molecular weight of polymers is an important parameter influencing oxygen and nutrient diffusion, the kinetics of hydrogel formation, rigidity, rheology, elastic moduli, and other mechanical properties crucial for long-term utilization. A comparison of stability and enzymatic activity between immobilized enzymes and their free native counterparts was explored. The discussion was not limited to recent advancements in the biopharmaceutical field, such as microorganism or enzyme immobilization, but also extended to methods used in sensor and biosensor applications. In this study, we present data on the advantages of cell and enzyme immobilization over microorganism (bacteria and fungi) suspension states to produce various bioproducts and metabolites—such as antibiotics, enzymes, and precursors—and determine the efficiency of immobilization processes and the optimal conditions and process parameters to maximize the yield of the target products. Full article

Background: A pelletizer paired with hot-melt extrusion technology (HME) was used to develop colon-targeted pellets for ketoprofen (KTP). Thermal stability and side effects in the upper gastrointestinal tract made ketoprofen more suitable for this work. Methods: The pellets were prepared using the enzyme-triggered polymer Pectin LM in the presence of HPMC HME 4M, followed by pH-dependent Eudragit^® S 100 coating to accommodate the maximum drug release in the colon by minimizing drug release in the upper gastrointestinal tract (GIT). Box–Behnken Design (BBD) was used for response surface optimization of the proportion of different independent variables like Pectin LM (A), HPMC HME 4M (B), and Eudragit^® S 100 (C) required to lower the early drug release in upper GIT and to extend the drug release in the colon. Results: Solid-state characterization studies revealed that ketoprofen was present in a solid solution state in the hot-melt extruded polymer matrix. The desired responses of the prepared optimized KTP pellets obtained by considering the designed space showed 1.20% drug release in 2 h, 3.73% in the first 5 h of the lag period with the help of Eudragit^® S 100 coating, and 93.96% in extended release up to 24 h in the colonic region. Conclusions: Hence, developing Eudragit-coated hot-melt extruded pellets could be a significant method for achieving the colon-specific release of ketoprofen. Full article

Inflammatory Bowel Disease (IBD) is a chronic condition that affects approximately 1.6 million Americans. While current polyphenols for treating IBD can be expensive and cause unwanted side effects, there is an opportunity regarding a new drug/polymer formulation using silymarin and an electrospray procedure. Silymarin is a naturally occurring polyphenolic flavonoid antioxidant that has shown promising results as a pharmacological agent due to its antioxidant and hepatoprotective characteristics. This study aims to produce a drug–polymer complex named the SILS100-Electrofiber complex, using an electrospray system. The vertical set-up of the electrospray system was optimized at a 1:10 of silymarin and Eudragit^® S100 polymer to enhance surface area and microfiber encapsulation. The SILS100-Electrofiber complex was evaluated using drug release kinetics via UV Spectrophotometry, Fourier-Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM), and Differential Scanning Calorimetry (DSC). Drug loading, apparent solubility, and antioxidant activity were also evaluated. The study was successful in creating fiber-like encapsulation of the silymarin drug with strand diameters ranging from 5–7 μm, with results showing greater silymarin release in Simulated Intestinal Fluid (SIF) compared to Simulated Gastric Fluid (SGF). Moving forward, this study aims to provide future insight into the formulation of drug–polymer complexes for IBD treatment and targeted drug release using electrospray and microencapsulation. Full article

This study aimed to develop an effective oral formulation of semaglutide, a glucagon-like peptide-1 receptor agonist, using an organometallic phyllosilicate-based colonic delivery system. The core nanocomplex (AMP-Sema) of 3-aminopropyl-functionalized magnesium phyllosilicate (AMP) and semaglutide was prepared via electrostatic interactions. Subsequently, AMP-Sema was coated with a polymer showing pH-dependent solubility (Eudragit^® S100) for preferential colonic delivery. The surface-coated nanoparticles (EAMP-Sema) showed a narrow size distribution, and the encapsulated semaglutide maintained its conformational stability. The pH-dependent drug release property of EAMP-Sema yielded around 20% and 62% drug release at pH 1.2 and 7.4, respectively. The nanoparticles exhibited significantly decreased size and surface charge at pH 7.4, which indicated the pH-dependent dissolution of the coating layer. Furthermore, EAMP-Sema effectively improved the membrane permeability and metabolic stability of semaglutide in the gastrointestinal tract. It protected the encapsulated drugs from proteolysis in simulated intestinal fluids and increased drug transport by 2.5-fold in Caco-2 cells. Consequently, orally administered EAMP-Sema (equivalent to 8 mg/kg of semaglutide) showed significant therapeutic benefits, yielding effective glycemic control and weight loss in high-fat diet/streptozotocin (40 mg/kg)-induced type 2 diabetic rats. These results demonstrate that EAMP-Sema could improve the efficacy of orally administered semaglutide by enhancing the GI stability and cellular uptake of protein drugs. Full article

Curcumin and resveratrol are polyphenolic compounds that have been shown to exhibit synergistic therapeutic properties including anti-inflammatory, anticancer, and antiulcer activities, which may be exploited for the treatment of gastric diseases. However, both compounds have poor aqueous solubility and rapid metabolism, resulting in a low oral bioavailability. In situ gelling, liquid formulations were developed to produce a gastroretentive, raft-forming delivery vehicle to improve bioavailability. Solid dispersions containing a mixture of curcumin and resveratrol with Eudragit^® EPO (Cur/Res-SD) were first prepared using solvent evaporation, to improve the solubility and dissolution of the compounds. Solid dispersions of a weight ratio of 1:10 curcumin/resveratrol to Eudragit^® EPO were subsequently incorporated into in situ gelling, liquid formulations based on the gelling polymers, sodium alginate (low viscosity and medium viscosity), pectin, and gellan gum, respectively. Calcium carbonate and sodium bicarbonate were included to produce carbon dioxide bubbles in the gel matrix, on exposure to gastric fluid, and to achieve flotation. Moreover, the calcium ions acted as a crosslinking agent for the hydrogels. Optimized formulations floated rapidly (<60 s) in simulated gastric fluid (pH = 1.2) and remained buoyant, resulting in the gradual release of more than 80% of the curcumin and resveratrol content within 8 h. The optimized formulation based on medium-viscosity sodium alginate exhibited enhanced cytotoxic activity toward human gastric adenocarcinoma cell lines (AGS), compared with unformulated curcumin and resveratrol compounds, and increased anti-inflammatory activity against RAW 264.7 macrophage cells compared with the NSAID, indomethacin. These findings demonstrate that in situ gelling, liquid formulations, loaded with a combination of curcumin and resveratrol in the form of solid dispersions, show potential as gastroretentive delivery systems for local and systemic effects. Full article

Liraglutide (LIRA) is a glucagon-like peptide-1 (GLP-1) receptor agonist renowned for its efficacy in treating type 2 diabetes mellitus (T2DM) and is typically administered via subcutaneous injections. Oral delivery, although more desirable for being painless and potentially enhancing patient adherence, is challenged by the peptide’s low bioavailability and vulnerability to digestive enzymes. This study aimed to develop LIRA-containing zein-based nanoparticles stabilized with eudragit RS100 and chitosan for oral use (Z-ERS-CS/LIRA). These nanoparticles demonstrated a spherical shape, with a mean diameter of 238.6 nm, a polydispersity index of 0.099, a zeta potential of +40.9 mV, and an encapsulation efficiency of 41%. In vitro release studies indicated a prolonged release, with up to 61% of LIRA released over 24 h. Notably, the nanoparticles showed considerable resistance and stability in simulated gastric and intestinal fluids, suggesting protection from pH and enzymatic degradation. Pharmacokinetic analysis revealed that orally administered Z-ERS-CS/LIRA paralleled the pharmacokinetic profile seen with subcutaneously delivered LIRA. Furthermore, in vivo tests on a diabetic rat model showed that Z-ERS-CS/LIRA significantly controlled glucose levels, comparable to the results observed with free LIRA. The findings underscore Z-ERS-CS/LIRA nanoparticles as a promising approach for oral LIRA delivery in T2DM management. Full article