Cross-Linked Thiolated Hydroxypropil-ß-Cyclodextrin for Pulmonary Drug Delivery.

Inhalable formulations with cyclodextrins (CDs) as solubility and absorption enhancers show promise for pulmonary delivery. Thiolated hydroxypropyl-ß-cyclodextrin (HP-ß-CD-SH) has mucoadhesive properties, enhancing drug absorption. Moreover, it has self-aggregation capability, which could further improve absorption and drug stability, as well as reduce irritation. This study aims to stabilize CD nanoaggregates using bifunctional cross-linkers and evaluate their benefits for lung drug delivery compared to pristine HP-ß-CD-SH. METHODS: The effectiveness of cross-linked HP-ß-CD-SH nanoparticles (HP-ß-CD-SH-NP) was compared to transient nanoaggregates in enhancing the activity of dexamethasone (DMS) and olive leaf extracts (OLE). DMS, a poorly soluble drug commonly used in lung treatments, and OLE, known for its antioxidant properties, were chosen. Drug-loaded HP-ß-CD-SH-NP were prepared and nebulized onto a lung epithelial Air-Liquid Interface (ALI) model, assessing drug permeation and activity. RESULTS: HP-ß-CD-SH with 25% thiolation was synthesized via microwave reaction, forming 150 nm nanoaggregates and stabilized 400 nm HP-ß-CD-SH-NP. All carriers showed good complexing ability with DMS and OLE and were biocompatible in the lung ALI model. HP-ß-CD-SH promoted DMS absorption, while stabilized HP-ß-CD-SH-NP protected against oxidative stress. CONCLUSION: HP-ß-CD-SH is promising for lung delivery, especially as stabilized nanoaggregates, offering versatile administration for labile molecules like natural extracts.

Enhanced mucoadhesive properties of ionically cross-linked thiolated gellan gum films.

Localized oral drug delivery offers several advantages for treating various disease conditions. However, drug retention at the disease site within the oral cavity is indeed a significant challenge due to the dynamic oral environment. The present study aimed to develop a mucoadhesive inner layer for a three-layer mucoadhesive bandage suitable for localized oral drug delivery. using gellan gum (GG) biopolymer. Gellan gum (GG) was modified using L-cysteine moieties via carbodiimide chemistry. Subsequently, gellan gum solution at different extents of thiolation was ionically cross-linked using aluminum ammonium sulfate. Thiolated gellan gum films of uniform thickness were prepared using a solvent casting method. The thickness of bare gellan gum film was 0.035 ± 0.0043 mm, whereas the thiolated gellan gum films, GG 1S and GG 2S showed a thickness of 0.0191 ± 0.0011 mm and 0.0188 ± 0.0004 mm respectively. A high work of adhesion was noted for thiolated gellan gum (GG 2S) with a value of 10 N.mm while using porcine buccal mucosa. An average tensile strength of 48.2 ± 2.46 MPa was measured for thiolated gellan gum films irrespective of the extent of thiolation. The high work of adhesion, favorable cytocompatibility, desirable mechanical properties, and free swell capacity in saline confirmed the suitability of ionically cross-linked thiolated gellan gum films as an inner mucoadhesive layer for the mucoadhesive bandage.

Biopharmaceutical studies of a novel sedative sublingual lozenge based on glycine and tryptophan: A rationale for mucoadhesive agent selection.

Effective sedative drugs are in great demand due to increasing incidence of nervous disorders. The present work was aimed to develop a novel sublingual sedative drug based on glycine and L-tryptophan amino acids. Carbopol and different hydroxypropyl methylcellulose species were alternatively tested as mucoadhesive agents intended to prolong tryptophan sublingual release time. A model lipid medium of fully hydrated L-α-dimyristoylphosphatidylcholine was used for optimal mucoadhesive agents selection. Simultaneous processes of drug release and diffusion in lipid medium were first investigated involving both experimental and theoretical approaches. Individual substances, their selected combinations as well as different drug formulations were consecutively examined. Application of kinetic differential scanning calorimetry method allowed us to reveal a number of specific drug-excipient effects. Lactose was found to essentially facilitate tryptophan release and provide its ability to get into the bloodstream simultaneously with glycine, which is necessary to achieve glycine-tryptophan synergism. Introduction of a mucoadhesive agent into the formulation was shown to change kinetics of drug-membrane interactions variously depending on viscosity grade. Among the mucoadhesive agents, hydroxypropyl methylcellulose species K4M and E4M were shown to further accelerate drug release, therefore they were selected as optimal. Thus, effectiveness of the novel sedative drug was provided by including some excipients, such as lactose and the selected mucoadhesive agent species. A dynamic mathematical model was developed properly describing release and diffusion in lipid medium of various drug substances. Our study clearly showed applicability of a lipid medium to meet challenges such as drug-excipient interactions and optimization of drug formulations.

Journey of dietary fiber along the gastrointestinal tract: role of physical interactions, mucus, and biochemical transformations.

Dietary fiber-rich foods have been associated with numerous health benefits, including a reduced risk of cardiovascular and metabolic diseases. Harnessing the potential to deliver positive health outcomes rests on our understanding of the underlying mechanisms that drive these associations. This review addresses data and concepts concerning plant-based food functionality by dissecting the cascade of physical and chemical digestive processes and interactions that underpin these physiological benefits. Functional transformations of dietary fiber along the gastrointestinal tract from the stages of oral processing and gastric emptying to intestinal digestion and colonic fermentation influence its capacity to modulate digestion, transit, and commensal microbiome. This analysis highlights the significance, limitations, and challenges in decoding the complex web of interactions to establish a coherent framework connecting specific fiber components' molecular and macroscale interactions across multiple length scales within the gastrointestinal tract. One critical area that requires closer examination is the interaction between fiber, mucus barrier, and the commensal microbiome when considering food structure design and personalized nutritional strategies for beneficial physiologic effects. Understanding the response of specific fibers, particularly concerning an individual's physiology, will offer the opportunity to exploit these functional characteristics to elicit specific, symptom-targeting effects or use fiber types as adjunctive therapies.

Polyphenol-Enabled 2D Nanopatch for Enhanced Nasal Mucoadhesion and Immune Activation.

The advancement of effective nasal mucoadhesive delivery faces challenges due to rapid mucociliary clearance (MCC). Conventional studies have employed mucoadhesive materials, mainly forming spherical nanoparticles, but these offer limited adhesion to the nasal mucosa. This study hypothesizes that a 2D nanoscale structure utilizing adhesive polyphenols can provide a superior strategy for countering MCC, aligning with the planar mucosal layers. We explore the use of tannic acid (TA), a polyphenolic molecule known for its adhesive properties and ability to form complexes with biomolecules. Our study introduces an unprecedented 2D nanopatch, assembled through the interaction of TA with green fluorescent protein (GFP), and cell-penetrating peptide (CPP). This 2D nanopatch demonstrates robust adhesion to nasal mucosa and significantly enhances immunoglobulin A secretions, suggesting its potential for enhancing nasal vaccine delivery. The promise of a polyphenol-enabled adhesive 2D nanopatch signifies a pivotal shift from conventional spherical nanoparticles, opening new pathways for delivery strategies through respiratory mucoadhesion.

Novel Acryloylated and Methacryloylated Nanocellulose Derivatives with Improved Mucoadhesive Properties.

In this work, three nanocellulose derivatives are synthesized with the aim of preparing new mucoadhesive materials. Nanocellulose is reacted with glycidyl methacrylate in dimethylsulphoxide, and with acryloyl and methacryloyl chloride in dimethylacetamide in the presence of 4-(N,N-dimethylamino)pyridine as a catalyst. These reactions are carried out under heterogeneous conditions, and the reaction products are characterized using various spectroscopic techniques, X-ray diffraction, atomic force microscopy, and thermogravimetric analysis. The Fourier-transform infrared spectra showed all the characteristic absorption bands typical for cellulose and also new peaks at 1720 cm-1 for the carbonyl group (C═O) and 1639, 812 cm-1 for the double bond (C═C). It is established that the crystal structure of the nanocellulose is slightly changed with derivatisation and the thermal stability of these derivatives increased. Mucoadhesive properties of nanocellulose and its derivatives is evaluated using the tensile test, rotating basket method, and fluorescence flow-through method. The retention of these polymers is evaluated on sheep oral mucosal tissue ex vivo using artificial saliva. Test results demonstrated that the new derivatives of nanocellulose have improved mucoadhesive properties compared to the parent nanocellulose.

Targeted Bioimaging of Microencapsulated Recombinant LAB Vector Expressing Fluorescent Reporter Protein: A Non-invasive Approach for Microbial Tracking.

Lactococcus lactis (L. lactis), the first genetically modified Generally Recognized As Safe (GRAS) category Lactic Acid producing Bacteria (LAB), is best known for its generalized health-promoting benefits and ability to express heterologous proteins. However, achieving the optimal probiotic effects requires a selective approach that would allow us to study in vivo microbial biodistribution, fate, and immunological consequences. Although the chemical conjugation of fluorophores and chromophores represent the standard procedure to tag microbial cells for various downstream applications, it requires a high-throughput synthesis scheme, which is often time-consuming and expensive. On the contrary, the genetic manipulation of LAB vector, either chromosomally or extra-chromosomally, to express bioluminescent or fluorescent reporter proteins has greatly enhanced our ability to monitor bacterial transit through a complex gut environment. However, with faster passage and quick washing out from the gut due to rhythmic contractions of the digestive tract, real-time tracking of LAB vectors, particularly non-commensal ones, remains problematic. To get a deeper insight into the biodistribution of non-commensal probiotic bacteria in vivo, we bioengineered L. lactis to express fluorescence reporter proteins, mCherry (bright red monomeric fluorescent protein) and mEGFP (monomeric enhanced green fluorescent protein), followed by microencapsulation with a mucoadhesive and biodegradable polymer, chitosan. We show that coating of recombinant Lactococcus lactis (rL. lactis) with chitosan polymer, cross-linked with tripolyphosphate (TPP), retains their ability to express the reporter proteins stably without altering the specificity and sensitivity of fluorescence detection in vitro and in vivo. Further, we provide evidence of enhanced intragastric stability by chitosan-TPP (CS) coating of rL. lactis cells, allowing us to study the spatiotemporal distribution for an extended time in the gut of two unrelated hosts, avian and murine. The present scheme involving genetic modification and chitosan encapsulation of non-commensal LAB vector demonstrates great promise as a non-invasive and intensive tool for active live tracking of gut microbes.

In Vitro and Ex Vivo Evaluation of Novel Methacrylated Chitosan-PNIPAAm-Hyaluronic Acid Hydrogels Loaded with Progesterone for Applications in Vaginal Delivery.

Miscarriage is defined as the loss of a pregnancy before 24 weeks and administration of progesterone in pregnancy has considerably decreased the risk of premature birth. Progesterone (PGT) starting from the luteal phase stabilizes pregnancy, promotes differentiation of the endometrium, and facilitates the implantation of the embryo. Within the present study, novel hybrid hydrogels based on chitosan methacrylate (CHT), hyaluronic acid (HA), and poly(N-isopropylacrylamide) (PNIPAAm) for vaginal delivery of progesterone were evaluated. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) for structural identity assessment and evaluation of their morphological aspects. The ability to swell, the release capacity, enzymatic degradation, cytotoxicity, and mucoadhesion were also reported. The characterized hydrogels demonstrated mucoadhesive properties in contact with the vaginal tissue of swine and bovine origin as substrates, and biodegradability and controlled release in a simulated vaginal environment. Cytocompatibility tests confirmed the ability of the hydrogels and progesterone to support cell viability and growth. The results showed pH-dependent behavior, controlled drug release, good cytocompatibility, and mucoadhesive properties. The hydrogels with higher chitosan amounts demonstrated better bioadhesive properties. This study provides insights into the potential of these hydrogels for the controlled vaginal delivery of progesterone, with promising therapeutic effects and no cytotoxicity observed. The experimental results indicated that a composition with a moderate content of PNIPAAm was suitable for the controlled delivery of progesterone.

Synthesis of Thiomer/Nanoclay Nanocomposites as a Potential Drug Carrier: Evaluation of Mucoadhesive and Controlled Release Properties.

Novel thiomer/nanoclay nanocomposites based on a thiomer and montmorillonite (MMT) were prepared in order to obtain a mucoadhesive material with controlled release properties for its potential use as drug carrier. The thiomer was synthesized by immobilization of L-cysteine in alginate mediated by carbodiimide reaction and further characterized by FT-IR and Ellman's reaction. Nanocomposites with growing concentrations of thiomer and MMT were prepared and analyzed by XRD, TGA and TEM. Rheological behavior of nanocomposite in contact with mucin and intestinal mucus were studied as in vitro and in situ mucoadhesion approach, showing until ∼10-fold increasing in the complex viscosity and ∼27-fold in elastic modulus when the amount of thiomer is increased. Higuchi and Korsmeyer-Peppas kinetic models were evaluated in order to study the release of deltamethrin from nanocomposite films. Release profiles showed a retard in the migration of the drug influenced by the amount of MMT (P < 0.05). Diffusion coefficient (D) showed a significant decrease (P < 0.0001) when concentration of MMT is increased reaching D = 4.18 × 10-7 m2 h-1, which resulted ∼7-fold lower in comparison with formulation without MMT. This hybrid nanocomposite can be projected as a potential mucoadhesive drug carrier with controlled release properties.

Synthesis and Characterization of Thiolated Nanoparticles Based on Poly (Acrylic Acid) and Algal Cell Wall Biopolymers for the Delivery of the Receptor Binding Domain from SARS-CoV-2.

The COVID-19 pandemic required great efforts to develop efficient vaccines in a short period of time. However, innovative vaccines against SARS-CoV-2 virus are needed to achieve broad immune protection against variants of concern. Polymeric-based particles can lead to innovative vaccines, serving as stable, safe and immunostimulatory antigen delivery systems. In this work, polymeric-based particles called thiolated PAA/Schizo were developed. Poly (acrylic acid) (PAA) was thiolated with cysteine ethyl ester and crosslinked with a Schizochytrium sp. cell wall fraction under an inverse emulsion approach. Particles showed a hydrodynamic diameter of 313 ± 38 nm and negative Zeta potential. FT-IR spectra indicated the presence of coconut oil in thiolated PAA/Schizo particles, which, along with the microalgae, could contribute to their biocompatibility and bioactive properties. TGA analysis suggested strong interactions between the thiolated PAA/Schizo components. In vitro assessment revealed that thiolated particles have a higher mucoadhesiveness when compared with non-thiolated particles. Cell-based assays revealed that thiolated particles are not cytotoxic and, importantly, increase TNF-α secretion in murine dendritic cells. Moreover, immunization assays revealed that thiolated PAA/Schizo particles induced a humoral response with a more balanced IgG2a/IgG1 ratio. Therefore, thiolated PAA/Schizo particles are deemed a promising delivery system whose evaluation in vaccine prototypes is guaranteed.

A Protocol for Preparing Mucoadhesive Emulsion Microgels and Assessing Their Mucoadhesion Properties In Vitro.

Intravesical instillation is an efficient therapeutic technique based on targeted administration of a drug directly into the lesion for the treatment of bladder diseases. This is an alternative to traditional systemic administration of drugs. However, this technique requires repeated procedures, which can lead to even greater inflammation and infection of the urethra. To date, novel systems that allow prolonged drug retention in the bladder cavity are actively being developed. We recently reported a targeted drug delivery system based on the mucoadhesive emulsion microgels consisting of the natural component whey protein isolate. Such micron-sized carriers possess high loading capacity, a prolonged drug release profile, and efficient mucoadhesive properties to the bladder urothelium. As a continuation of this work, we present a protocol for the synthesis of mucoadhesive emulsion microgels. Detailed procedures for preparing precursor solutions as well as studying the physico-chemical parameters of microgels (including loading capacity and drug release rate) and the mucoadhesive properties using the model of porcine bladder urothelium are discussed. Precautionary measures and nuances that are worth paying attention to during each experimental stage are given as well. Key features • The protocol for the synthesis of mucoadhesive emulsion microgels based on whey protein isolate is presented. The experimental conditions of emulsion microgels synthesis are discussed. • Methods for studying the physico-chemical properties of mucoadhesive emulsion microgels (size of emulsion microgels particles, loading capacity, release kinetics) are described. • The method for assessing mucoadhesive properties of emulsion microgels is demonstrated using the porcine bladder tissue model ex vivo.

Chitosan and liposomal delivery systems for epicatechin or propyl gallate targeting localized treatment of vulvovaginal candidiasis.

Natural polyphenols are promising alternatives to antifungals for novel treatments of vulvovaginal candidiasis (VVC) in an era of antimicrobial resistance. However, polyphenols are poorly soluble and prone to degradation. To overcome their limitations, we propose incorporation in liposomes. The study aimed to develop chitosan and liposome comprising delivery systems for epicatechin (EC) or propyl gallate (PG) as treatment of VVC. EC was selected for its antioxidative properties and PG as an ester of antifungal gallic acid. To improve formulation retention at vaginal site, mucoadhesive chitosan was introduced into formulation as liposomal surface coating or hydrogel due to intrinsic antifungal properties. These polyphenol-loaded liposomes exhibited an average size of 125 nm with a 64 % entrapment efficiency (for both polyphenols). A sustained in vitro polyphenol release was seen from liposomes, particularly in chitosan hydrogel (p < 0.01 or lower). Viscosity was evaluated since increased viscosity upon mucin contact indicated adhesive bond formation between chitosan and mucin confirming mucoadhesiveness of formulations. Antifungal activity was evaluated by the broth microdilution method on Candida albicans CRM-10231. Unlike PG, incorporation of EC in liposomes enabled antifungal activity. Fungicidal activity of chitosan was confirmed both when used as liposomal coating material and as hydrogel vehicle.

Association of mucoadhesive polymeric matrices and liposomes for local delivery of miconazole: A new approach for the treatment of oral candidiasis.

Since the local treatment of oral candidiasis usually requires long-term administration of the antifungal drug, an ideal dosage form should be able to maintain the drug release over an extended period, assuring an adequate concentration at the infection site. In this context, we have considered the possibility of a buccal delivery of miconazole nitrate (MN) by mucoadhesive polymeric matrices. The loading of the antifungal drug in a hydrophilic matrix was made possible by taking advantage of the amphiphilic nature of liposomes (LP). The MN-loaded LP were prepared by a thin film evaporation method followed by extrusion, while solid matrices were obtained by freeze-drying a suspension of the LP in a polymeric solution based on chitosan (CH), sodium hyaluronate (HYA), or hydroxypropyl methylcellulose (HPMC). MN-loaded LP measured 284.7 ± 20.1 nm with homogeneous size distribution, adequate drug encapsulation efficiency (86.0 ± 3.3 %) and positive zeta potential (+47.4 ± 3.3). CH and HYA-based formulations almost completely inhibited C. albicans growth after 24 h, even if the HYA-based one released a higher amount of the drug. The CH-based matrix also provided the best mucoadhesive capacity and therefore represents the most promising candidate for the local treatment of oral candidiasis.

In vitro Models for Predicting Bioadhesion Fracture Strength to Ex Vivo Animal Buccal Tissue.

Commitment to the 3Rs principle (Replacement, Reduction, and Refinement) led to the development of a cell-based system to measure buccal bioadhesion in vitro and replace the use of porcine buccal and esophageal tissues (PBT and PET, respectively). Additionally, the aim is to bridge the gap in knowledge regarding the bioadhesion properties of PBT and PET. The in vitro models are based on the human buccal epithelial cell line-TR146 without ("Model I") or with ("Model II") 5% (w/v) mucous layer. The in vitro setup also provides a method to evaluate the bioadhesion between two soft materials. Standard bioadhesive hydrogels (alginate, chitosan, and gelatin) are used to test and compare the results from the in vitro models to the ex vivo tissues. The ex vivo and in vitro models show increased bioadhesion as the applied force and contact time increases. Furthermore, Model I exhibits bioadhesion values-of alginate, chitosan, and gelatin-comparable to those obtained with PBT. It is also found that contact time and applied force similarly affect PBT and PET bioadhesion, while PET exhibits greater values. In conclusion, Model I can replace PBT for measuring bioadhesion and be incorporated into the experimental design of bioadhesive DDS, thus minimizing animal tissue usage.

Intestinal Targeted Nanogel with Broad-Spectrum Autonomous ROS Scavenging Performance for Enhancing the Bioactivity of trans-Resveratrol.

Introduction: To improve the bioavailability of trans-resveratrol (trans-Res), it is commonly co-delivered with antioxidant bioactives using a complex synthetic intestinal targeted carrier, however, which makes practical application challenging. Methods: A nanogel (Ngel), as broad-spectrum autonomous ROS scavenger, was prepared using selenized thiolated sodium alginate (TSA-Se) and crosslinked with calcium lactate (CL) for loading trans-Res to obtain Ngel@Res, which maintained spherical morphology in the upper digestive tract but broke down in the lower digestive tract, resulting in trans-Res release. Results: Under protection of Ngel, trans-Res showed enhanced stability and broad-spectrum ROS scavenging activity. The synergistic mucoadhesion of Ngel prolonged the retention time of trans-Res in the intestine. Ngel and Ngel@Res increased the lifespan of Caenorhabditis elegans to 26.00 ± 2.17 and 26.00 ± 4.27 days by enhancing the activity of antioxidases, upregulating the expression of daf-16, sod-5 and skn-1, while downregulating the expression of daf-2 and age-1. Conclusion: This readily available, intestinal targeted selenized alginate-based nanogel effectively improves the bioactivity of trans-Res.

Enhancing mucoadhesion: Exploring rheological parameters and texture profile in starch solutions, with emphasis on micro-nanofiber influence.

This comprehensive analysis explores the rheological parameters and texture profile analysis (TPA) to effect starch solutions for mucoadhesion and assess the impact of micro-nanofibers (MNFs) on these parameters. The surface chemistry of all six samples was examined through the Fourier transform infrared (FTIR) technique. The spectrum of FTIR was recorded in the range of 500-4000 cm-1. The viscosity of different pHs (2-11) and temperatures (20-70 °C) of verious starches, potato, corn, and rice, decreased with the increasing of shear rate, exhibiting shear thinning behavior, which conformed to pseudoplastic fluid.The combination of chitosan and collagen MNFs significantly changed rheological properties, and the sample with the addtion of 1500 µL CC-MNF exhibited a greater viscosity of 59.8 mPa·s at a shear rate of 1.49 s-1. Potato starch emerged as a strong candidate for mucoadhesion due to its low hardness (4.62 ± 0.31 N), high adhesion (0.0322 ± 0.0053 mJ), cohesiveness (0.37 ± 0.03 Ratio), low chewiness (0.66 ± 0.12 mJ), and gumminess (1.69 ± 0.23 N). The inclusion of MNFs, especially collagen/chitosan MNFs showed the potential to further enhance adhesion.

A thiolated oxidized guar gum and sodium alginate dual-network microspheres with enhanced gastric acid resistance and mucoadhesion for delivery of probiotics.

Probiotics offer numerous beneficial functions for human bodies, while the low survival rate under gastric acid and short retention time in the intestine are the major obstacles to their utilization. To address these issues, we designed a novel dual-network hydrogel microsphere that combines gastric acid resistance with enhanced mucoadhesion, aiming for the targeted delivery of probiotics. Thiolated oxidized guar gum (SOGG) was disulfide-linked to form the first network, and sodium alginate (SA) was cross-linked with Ca2+ to form the second network. Under the protection of the interpenetrating dual network microspheres, a much higher viability of Lactobacillus rhamnosus (LGG) (8.73 log CFU/mL) was achieved in simulated gastric fluid, compared to the zero-survival rate of free LGG. Mucoadhesion tests showed that the adhesion rate of SOGG/SA microspheres to the intestinal mucosa was 1.75 times higher than that of thiol-free microspheres. In vivo studies revealed that LGG-loaded microspheres significantly enhanced intestinal barrier function, remodeled the gut microbiome, and alleviated DSS-induced colitis in mice. Overall, SOGG/SA microspheres provide an effective strategy to the challenges of probiotic reduction in the stomach and rapid expulsion from the intestines, enhancing their health benefits.

Mucoadhesive Budesonide Solution for the Treatment of Pediatric Eosinophilic Esophagitis.

Eosinophilic Esophagitis is an antigen-mediated inflammatory disease characterized by thickening of the esophageal wall, leading to dysphagia, vomiting, reflux, and abdominal pain. This disease can be treated with a therapeutic approach ranging from diet to pharmacological therapy. Jorveza® (budesonide) and Dupixent® (dupilumab) are treatments for Eosinophilic Esophagitis approved by the European Medicines Agency in adults but not in children. Budesonide-based extemporaneous oral liquid suspensions could be prepared for pediatric use. The main limit of this formulation is that budesonide needs a longer residence time on the esophageal mucosa to solubilize and diffuse in it to exert its local anti-inflammatory effect. Herein, we propose the development of an extemporaneous mucoadhesive oral budesonide solution for the pediatric population. A liquid vehicle containing hydroxypropyl-beta-cyclodextrin as a complexing agent and carboxymethylcellulose sodium as a mucoadhesive excipient was used to prepare budesonide-based formulations. A stable solution at a concentration of 0.7 mg/mL was successfully prepared and characterized. The formulation showed rheological and mucoadhesive properties suitable for an Eosinophilic Esophagitis local prolonged treatment. In this way, pharmacists can prepare stable budesonide-based mucoadhesive solutions, providing both patients and physicians with a new therapeutic option for Eosinophilic Esophagitis pediatric treatment.

Optimizing anthocyanin Oral delivery: Effects of food biomacromolecule types on Nanocarrier performance for enhanced bioavailability.

Wall material types influence the efficacy of nanocarriers in oral delivery systems. We utilized three food biomacromolecules (whey protein isolate, oxidized starch, lipids) to prepare three types of nanocarriers. Our aim was to investigate their performance in digestion, cellular absorption, mucus penetration, intestinal retention, and bioavailability of the encapsulated anthocyanins (Ant). The release rate of protein nanocarriers (Pro-NCs) was twice that of starch nanocarriers (Sta-NCs) and four times that of lipid nanocarriers (Lip-NCs) in simulated gastrointestinal fluid. Additionally, Pro-NCs demonstrated superior transmembrane transport capacity and over three times cellular internalization efficiency than Sta-NCs and Lip-NCs. Sta-NCs exhibited the highest mucus-penetrating capacity, while Pro-NCs displayed the strongest mucoadhesion, resulting in extended gastrointestinal retention time for Pro-NCs. Sta-NCs significantly enhanced the in vivo bioavailability of Ant, nearly twice that of free Ant. Our results demonstrate the critical role of wall material types in optimizing nanocarriers for the specific delivery of bioactive compounds.

Biopolymer Drug Delivery Systems for Oromucosal Application: Recent Trends in Pharmaceutical R&D.

Oromucosal drug delivery, both local and transmucosal (buccal), is an effective alternative to traditional oral and parenteral dosage forms because it increases drug bioavailability and reduces systemic drug toxicity. The oral mucosa has a good blood supply, which ensures that drug molecules enter the systemic circulation directly, avoiding drug metabolism during the first passage through the liver. At the same time, the mucosa has a number of barriers, including mucus, epithelium, enzymes, and immunocompetent cells, that are designed to prevent the entry of foreign substances into the body, which also complicates the absorption of drugs. The development of oromucosal drug delivery systems based on mucoadhesive biopolymers and their derivatives (especially thiolated and catecholated derivatives) is a promising strategy for the pharmaceutical development of safe and effective dosage forms. Solid, semi-solid and liquid pharmaceutical formulations based on biopolymers have several advantageous properties, such as prolonged residence time on the mucosa due to high mucoadhesion, unidirectional and modified drug release capabilities, and enhanced drug permeability. Biopolymers are non-toxic, biocompatible, biodegradable and may possess intrinsic bioactivity. A rational approach to the design of oromucosal delivery systems requires an understanding of both the anatomy/physiology of the oral mucosa and the physicochemical and biopharmaceutical properties of the drug molecule/biopolymer, as presented in this review. This review summarizes the advances in the pharmaceutical development of mucoadhesive oromucosal dosage forms (e.g., patches, buccal tablets, and hydrogel systems), including nanotechnology-based biopolymer nanoparticle delivery systems (e.g., solid lipid particles, liposomes, biopolymer polyelectrolyte particles, hybrid nanoparticles, etc.).