A mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery.

Intravesical therapy (IT) is widely used to tackle various urological diseases. However, its clinical efficacy is decreased by the impermeability of various barriers presented on the bladder luminal surface, including the urinary mucus layer and the densely packed tissue barrier. In this study, we report a mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery. Upon intravesical instillation, its poloxamer 407 (PLX) hydrogel gelated and adhered to the urothelium to prolong its intravesical retention. The urea afterwards diffused into the hydrogel, thus generating a concentration gradient. Urease-powered membrane nanomotors (UMN) without asymmetric surface engineering could catalyze the urea and migrate down this concentration gradient to deeply and unidirectionally penetrate the urothelial barrier. Moreover, the intravesical hybrid system-delivered gemcitabine could effectively inhibit the bladder tumor growth without inducing any side effect. Therefore, our mucoadhesive-to-penetrating nanomotors-in-hydrogel system could serve as an alternative to IT to meet the clinical need for more efficacious therapeutics for urological diseases.

Timolol Maleate in Situ Ophthalmic Mucoadhesive-Thermosensitive Gel: Development and Characterization.

Objectives: The aim of this study was to prepare a sustained-delivery mucoadhesive-thermosensitive formulation containing poloxamer 338 (P338), poloxamer 188 (P188), and mucoadhesive agents, such as chitosan (CHT) and carboxymethylcellulose (CMC), to increase the ophthalmic bioavailability of timolol maleate (TM). Materials and Methods: Gels were prepared by mixing different amounts of P338, P188, and a mucoadhesive agent in cold isotonic water using a magnetic stirrer. The sol-gel gelation time of the gels was determined using the test tube inversion method. Viscosity measurements and analysis of the mechanical properties of the gel formulations were performed. In vitro release using dialysis membranes and ex vivo permeation studies using fresh-warmed cow eyes were performed. Results: The gelation times of formulations containing 20:2.5 (P338:P188) and 0.1% CMC and formulations containing 20:2.5 (P338:P188) and 0.1% CHT were 35 s and 26.67 s, respectively. An optimally selected CHT mucoadhesive-thermosensitive in situ gelling system can successfully control the release of moderately hydrophilic drugs, such as TM. In the viscosity study, both formulations showed Newtonian fluid, and the CHT gel's viscosity was found to be higher. The CHT gel showed better mechanical properties than the CMC gel. The amount of TM penetrating the cow cornea after 24 hours was 73.38%, 71.80%, 67.25%, and 60.55% from the CHT gel, CMC gel, TM solution, and commercial preparation, respectively. Conclusion: The improved mucoadhesive-thermosensitive in situ gelling system successfully controlled the release of TM. The significantly lower drainage of TM into the circulation compared with eye drops is an advantage in treating glaucoma, and the use of mucoadhesive agents increases drug penetration.

Thermosensitive chitosan-based hydrogel: a vehicle for overcoming the limitations of nose-to-brain cell therapy.

Cell therapy is a promising strategy for treating neurological pathologies but requires invasive methods to bypass the blood-brain barrier restrictions. The nose-to-brain route has been presented as a direct and less invasive alternative to access the brain. The primary limitations of this route are low retention in the olfactory epithelium and poor cell survival in the harsh conditions of the nasal cavity. Thus, using chitosan-based hydrogel as a vehicle is proposed in this work to overcome the limitations of nose-to-brain cell administration. The hydrogel's design was driven to achieve gelification in response to body temperature and a mucosa-interacting chemical structure biocompatible with cells. The hydrogel showed a <30 min gelation time at 37°C and >95% biocompatibility with 2D and 3D cultures of mesenchymal stromal cells. Additionally, the viability, stability, and migration capacity of oligodendrocyte precursor cells (OPCs) within the hydrogel were maintained in vitro for up to 72 hours. After the intranasal administration of the OPCs-containing hydrogel, histological analysis showed the presence of viable cells in the nasal cavity for up to 72 hours post-administration in healthy athymic mice. These results demonstrate the hydrogel's capacity to increase the residence time in the nasal cavity while providing the cells with a favorable environment for their viability. This study presents for the first time the use of thermosensitive hydrogels in nose-to-brain cell therapy, opening the possibility of increasing the delivery efficiency in future approaches in translational medicine. STATEMENT OF SIGNIFICANCE: : This work highlights the potential of biomaterials, specifically hydrogels, in improving the effectiveness of cell therapy administered through the nose. The nose-to-brain route has been suggested as a non-invasive way to directly access the brain. However, delivering stem cells through this route poses a challenge since their viability must be preserved and cells can be swept away by nasal mucus. Earlier attempts at intranasal cell therapy have shown low efficiency, but still hold promise to the future. The hydrogels designed for this study can provide stem cells with a biocompatible environment and adhesion to the nasal atrium, easing the successful migration of viable cells to the brain.

Synthesis and biological applications of nanocomposite hydrogels based on the methacrylation of hydroxypropyl methylcellulose and lignin loaded with alpha-pinene.

Oral conditions, such as recurrent aphthous stomatitis, are chronic inflammatory disorders that significantly affect the life quality. This study aims to develop a novel buccal mucoadhesive based on methacrylate hydroxypropyl methylcellulose (M-HPMC) and methacrylate lignin (M-SLS) encapsulated with nanostructured lipid carriers (NLCs) for controlled release of alpha-pinene (α-pinene). NLCs with particle sizes of 152 ± 3 nm were prepared by using stearic acid and oleic acid as solid and liquid lipids, respectively. Following the successful synthesis of M-HPMC and M-SLS, various concentrations of α-pinene loaded NLCs (0, 18, 38, and 50 wt%) were encapsulated in M-HPMC/M-SLS hydrogel. It was demonstrated that the physiological and mechanical performances of hydrogels were changed, depending on the NLC content. Remarkably, the incorporation of 18 wt% NLC improved the compressive strength (143 ± 14 kPa) and toughness (17 ± 1 kJ/m3) of M-HPMC/M-SLS hydrogel. This nanocomposite hydrogel considerably decreased dissipated energy from 1.64 kJ/m3 to 0.99 kJ/m3, after a five-cycle compression test. The nanocomposite hydrogel exhibited controlled α-pinene release for up to 96 h which could significantly improve the antioxidant activity of M-HPMC/M-SLS matrix. Moreover, the reinforcing M-HPMC/M-SLS hydrogel with α-pinene-loaded NLCs resulted in increased adhesive strength (113.5 ± 7.5 kPa) to bovine buccal mucosa and cytocompatibility in contact with fibroblasts.

Design of experiment (DoE) of mucoadhesive valproic acid-loaded nanostructured lipid carriers (NLC) for potential nose-to-brain application.

Epilepsy is a highly prevalent neurological disease and valproic acid (VPA) is used as a first-line chronic treatment. However, this drug has poor oral bioavailability, which requires the administration of high doses, resulting in adverse effects. Alternative routes of VPA administration have therefore been investigated, such as the nose-to-brain route, which allows the drug to be transported directly from the nasal cavity to the brain. Here, the use of nanostructured lipid carriers (NLC) to encapsulate drugs administered in the nasal cavity has proved advantageous. The aim of this work was to optimise a mucoadhesive formulation of VPA-loaded NLC for intranasal administration to improve the treatment of epilepsy. The Design of Experiment (DoE) was used to optimise the formulation, starting with component optimisation using Mixture Design (MD), followed by optimisation of the manufacturing process parameters using Central Composite Design (CCD). The optimised VPA-loaded NLC had a particle size of 76.1 ± 2.8 nm, a polydispersity index of 0.190 ± 0.027, a zeta potential of 28.1 ± 2.0 mV and an encapsulation efficiency of 85.4 ± 0.8%. The in vitro release study showed VPA release from the NLC of 50 % after 6 h and 100 % after 24 h. The in vitro biocompatibility experiments in various cell lines have shown that the optimised VPA-loaded NLC formulation is safe up to 75 µg/mL, in neuronal (SH-SY5Y), nasal (RPMI 2650) and hepatic (HepG2) cells. Finally, the interaction of the optimised VPA-loaded NLC formulation with nasal mucus was investigated and mucoadhesive properties were observed. The results of this study suggest that the use of intranasal VPA-loaded NLC may be a promising alternative to promote VPA targeting to the brain, thereby improving bioavailability and minimising adverse effects.

Optimization and comparison of unidirectional lidocaine-loaded buccal patch with the articaine-loaded buccal patch to reduce injection pain and increment of patients' compliance in dental procedures: A double-blind randomized controlled trial.

Introduction: Nervous patients often postpone dental visits until they are in severe pain, exacerbating anxiety. Buccal patches provide a noninvasive method of delivering drugs between the upper gum and cheek, offering local and systemic effects. Prior research has demonstrated the effectiveness, safety, and reliability of topical lidocaine or articaine patches for oral anesthesia. Consequently, this study aimed to develop a three-layered buccal drug delivery system for topical anesthetics. Methods: The first step was preparing and optimizing lidocaine-loaded three-layer patches using Design-expert software. The effects of ethylcellulose, Eudragit, and carbopol concentrations were investigated on patch characteristics, including mucoadhesion, Young's modulus, and Elongation-at-break. Subsequently, patches were fabricated according to the optimized formulation determined by the software, and their efficacy was studied in a randomized, double-blind clinical trial. Participants received either lidocaine or articaine-loaded compared with placebo in a split-mouth study. They evaluated their pain levels using the Visual Analogue Scale (VAS), and the onset and duration of action were recorded for each treatment. Results: According to the results, increasing ethyl cellulose and Eudragit concentrations improved mucoadhesion force (p < 0.05) while increasing ethyl cellulose and reducing Eudragit concentrations increased Young's modulus (p < 0.05). Increasing Carbopol and decreasing Eudragit concentrations also raised elongation at break significantly in the patch (p < 0.05). Treatment with lidocaine-loaded patches resulted in lower VAS scores and faster onset of action in patients than articaine-loaded patches. However, the duration of the effect was longer in the former(p < 0.001). Conclusion: Based on the responses' analysis, the formulation of the 3-layered buccal patch was optimized. This formulation comprised 4.72 % ethyl cellulose, 2 % Carbopol, and 5 % eudragit. Clinical evaluation results showed that loading the optimized formulation with lidocaine was more efficient in controlling the injection pain than articaine. Trial registration: This trial was prospectively registered with irct.behdasht.gov.ir (registration number: IRCT20210118050067N2) on Aug 19, 2022.

Modification of the Biorelevant Release Testing of Esophageal Applied Mucoadhesive Films and Development of Formulation Strategies to Increase the Mucosal Contact Time.

The increasing prevalence of esophageal disease highlights the clinical relevance of novel, long-lasting mucoadhesive oral dosage forms. The EsoCap device enables targeted local application of films in the esophagus. Biorelevant test systems such as EsoPeriDiss are essential for early formulation development. To this end, the developed and already described release model for simulating the esophagus is being further developed for its potential for biorelevant mapping of the application site through complete tempering and investigation of biorelevant release media. Particularly viscous saliva formulations led to an extension of the retention time. In addition, possible formulation strategies for increasing the retention time of esophageal applied films are being evaluated, such as different film thicknesses, polymer grades and the influence of different active ingredient properties on the retention time. For highly soluble active ingredients, the film thickness represents an option for extending the retention time, while for less soluble substances, the choice of polymer grade may be of particular interest.

Chitosan-based mucoadhesive films loaded with curcumin for topical treatment of oral cancer.

This study aimed to develop mucoadhesive chitosan-based films capable of enhancing the curcumin penetration into the oral mucosa to treat oral cancers. We developed three films containing medium molecular weight chitosan (190-310 KDa) and other excipients (polyvinyl alcohol, Poloxamer®407, and propylene glycol) that have proven to be compatible with each other and with curcumin in thermal analyses. The films were smooth, flexible, and precipitates free, with uniform weight and thickness, pH compatible with the oral mucosa, resistance to traction, and entrapped curcumin in a high proportion. They also exhibited necessary swelling and mucoadhesion for tissue adherence. Ex vivo penetration studies proved that the films significantly increased the penetration of curcumin into the oral mucosa compared to control, even when the mucosa was subjected to a condition of simulated salivation. Curcumin exhibited cytotoxic activity in vitro in the two head and neck cancer cell lines (FaDu, SCC-9) at doses close to those found in penetration studies with the films. When combined with radiotherapy, curcumin demonstrated superiority over single doses of radiotherapy at 4, 8, and 12 Gy. Therefore, the developed films may represent a promising alternative for the topical treatment of oral tumors.

Absorption enhancement strategies in chitosan-based nanosystems and hydrogels intended for ocular delivery: Latest advances for optimization of drug permeation.

Ophthalmic diseases can be presented as acute diseases like allergies, ocular infections, etc., or chronic ones that can be manifested as a result of systemic disorders, like diabetes mellitus, thyroid, rheumatic disorders, and others. Chitosan (CS) and its derivatives have been widely investigated as nanocarriers in the delivery of drugs, genes, and many biological products. The biocompatibility and biodegradability of CS made it a good candidate for ocular delivery of many ingredients, including immunomodulating agents, antibiotics, ocular hypertension medications, etc. CS-based nanosystems have been successfully reported to modulate ocular diseases by penetrating biological ocular barriers and targeting and controlling drug release. This review provides guidance to drug delivery formulators on the most recently published strategies that can enhance drug permeation to the ocular tissues in CS-based nanosystems, thus improving therapeutic effects through enhancing drug bioavailability. This review will highlight the main ocular barriers to drug delivery observed in the nano-delivery system. In addition, the CS physicochemical properties that contribute to formulation aspects are discussed. It also categorized the permeation enhancement strategies that can be optimized in CS-based nanosystems into four aspects: CS-related physicochemical properties, formulation components, fabrication conditions, and adopting a novel delivery system like implants, inserts, etc. as described in the published literature within the last ten years. Finally, challenges encountered in CS-based nanosystems and future perspectives are mentioned.

Buccal lidocaine mucoadhesive patches for pediatrics' teething pain: overcoming possible hazards of oral gels.

OBJECTIVES: The utilization of pharmaceutical products in pediatric medicine, while established for use in adults, often presents uncertainties due to differences in application for children. The FDA discourages the use of local anesthetic gels, notably lidocaine, for teething pain in pediatrics due to concerns regarding potential adverse effects if inadvertently swallowed excessively. Therefore, significant attention is being directed towards modifying available marketed products to make them suitable for pediatric use. Here, we introduce mucoadhesive patches that not only have an adjusted dose of lidocaine but also feature a controlled release profile to manage teething pain with prolonged effect. This design helps to prevent issues related to gel liquefaction and swallowing, thereby reducing the potential hazardous side effects of lidocaine in the pediatric population. METHODS: The study involved the development of controlled-release lidocaine HCl-loaded pellets forming a matrix for inclusion in mucoadhesive patches. Characterization was performed to ensure prolonged drug release, particularly during overnight use, aiming to improve pediatric patient compliance and enable precise dosing. KEY FINDINGS: The mucoadhesive patches exhibited sustained lidocaine release lasting 24 h, potentially offering overnight relief suitable for pediatric application. The analysis of lidocaine content revealed that the developed patches maintained stable levels compared to doses obtained from commercially available oral gels. This finding implies effective pain control without the need for frequent reapplications, alongside controlled doses that decrease the likelihood of side effects. CONCLUSION: The formulated medicated patches demonstrated consistent lidocaine content, effectively controlled drug release, and consequently, reduced the likelihood of undesired side effects when compared to oral gel administration.

Intranasally Inoculated SARS-CoV-2 Spike Protein Combined with Mucoadhesive Polymer Induces Broad and Long-Lasting Immunity.

Current mRNA vaccines against SARS-CoV-2 effectively induce systemic and cell-mediated immunity and prevent severe disease. However, they do not induce mucosal immunity that targets the primary route of respiratory infection, and their protective effects wane after a few months. Intranasal vaccines have some advantages, including their non-invasiveness and the additional ability to activate mucosal immunity. In this study, we aimed to explore the effectiveness of an intranasally inoculated spike protein of SARS-CoV-2 mixed with a carboxy-vinyl polymer (S-CVP), a viscous agent. Intranasally inoculated S-CVP strongly induced antigen-specific IgG, including neutralizing antibodies, in the mucosal epithelium and serum and cellular immunity compared to the spike protein mixed with aluminum potassium sulfate. Furthermore, IgA production was detected only with S-CVP vaccination. S-CVP-inoculation in mice significantly suppressed the viral load and inflammation in the lung and protected mice against SARS-CoV-2 challenges, including an early circulating strain and the Omicron BA.1 variant in a manner dependent on CD8+ cells and monocytes/neutrophils. Surprisingly, high antibody responses and protective effects against multiple variants of SARS-CoV-2, including Omicron BA.5, persisted for at least 15 months after the S-CVP immunization. Hence, we propose intranasal inoculation with S-CVP as a promising vaccine strategy against SARS-CoV-2.

Buccal Administration of a Zika Virus Vaccine Utilizing 3D-Printed Oral Dissolving Films in a Mouse Model.

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain-Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases.

Thermo-activated in situ rectal gel preparation for Ibuprofen using eutectic mixture.

This study aimed to develop a thermosensitive in situ gel formulation for rectal delivery of Ibuprofen as an efficient alternative dosage form. Utilizing poloxamer 188, poloxamer 407, and HPMC via cold technique method, a thermosensitive in situ gel was successfully prepared. The concentration of Ibuprofen in the formulations was 1.2 % (w/w). The prepared gels underwent assessment for clarity, gelation temperature, gelation time, gel strength, spread ability, syringe-ability, pH, viscosity, FTIR, and drug content. The selected formulations exhibited a gelation temperature within the range of 30 °C to 36 °C, with consistent amount of drug soluble in the formulations (93 % - 110 %). Mucoadhesive studies, in vitro release tests, ex vivo modeling of drug release, kinetic studies modeling, and histopathology testing were also conducted. The formulation comprising 18 % poloxamer 407, 12 % poloxamer 188, and 1 % sodium chloride (FS15) demonstrated suitable gelation temperature and desirable drug release rate. In vitro drug release tests indicated completion within one hour for both FS10 (20 % P407 & 10 % P188) and FS15 (18 % P407 & 12 % P188), with consistent and predictable release patterns observed through kinetic modeling analysis. Microscopic histopathology examination confirmed the safety of the selected formula, exhibiting no irritation in the mucosal membrane of the sheep. In conclusion, Ibuprofen thermosensitive in situ gel presents a promising and convenient strategy as a rectal carrier and an alternative dosage form to solid suppositories.

Bioadhesive and drug-loaded cellulose nanofiber/alginate film for healing oral mucosal wounds.

Recurrent oral ulcers are common oral mucosal lesions that severely reduce patients' quality of life. Commercial mucoadhesive films are easily disrupted due to oral movement and complex wet environments, thus reducing drug utilization and even causing toxic side effects. Herein, we report a mucoadhesive film composed of Ca2+-crosslinked carboxymethylated cellulose nanofibers and alginate, in which two drugs of dexamethasone (DXM) and dyclonine hydrochloride (DYC) are loaded for the treatment of oral ulcers. The wet films have a high Young's modulus of 7.1 ± 2.6 MPa and a large strain of 53.6 ± 9.8 % and adhere to tissue strongly, which allows them to resist the deformation caused by frequent oral movement. The films also have nice durability against water and excellent biocompatibility. Moreover, the drug release was controlled at different rates. The fast release of DYC facilitates the quick relief of pain, while the slow release of DXM benefits the long-term treatment of wounds. Finally, the animal experiment demonstrates the films displayed excellent therapeutic efficacy in healing oral ulcers.

Promising brain biodistribution of insulin via intranasal dry powder for nose-to-brain delivery.

Nose-to-brain delivery (NTBD) offering potential benefits for treating Alzheimer's disease. In previous research, insulin dry powder (IDP) formulation for NTBD was developed, exhibiting favorable stability. This study aims to conduct in vitro and ex vivo assessment of release, permeation, mucoadhesion and histopathology, as well as an in vivo biodistribution study to produce IDP for NTBD and evaluate brain biodistribution. Spray-freeze-dried IDP formulations with varying weight ratios of trehalose-to-inulin were produced and analyzed. The release study was carried out in PBS with a pH of 5.8 stirred at 50 rpm and maintained at 37 °C ± 0.5 °C. Goat nasal mucosa was used for ex vivo permeation and mucoadhesion testing under similar conditions. An ex vivo histopathological examination and an in vivo study using enzyme-linked immunosorbent assay, were also performed. The IDP dissolution study demonstrated complete release of all IDPs within 120 min. The permeation study indicated that steady-state conditions were observed between 30 and 240 min. The mucoadhesion study unveiled that IDP F5 exhibited the fastest mucoadhesion time and the least force required within the fastest time of 43.60 ± 2.57 s. The histopathological study confirmed that none of the tested IDPs induced irritation in the nasal mucosa. Furthermore, the biodistribution study demonstrated the absence of detectable insulin in the plasma, while IDP F3 exhibited the highest deposited concentration of insulin within both the olfactory bulb and the whole brain. The extensive evaluation of the IDP formulations through in vitro, ex vivo, and in vivo studies implies their strength non-invasive NTBD. IDP F3, with a 1:1 wt ratio of trehalose to inulin, exhibited favorable brain biodistribution outcomes and was recommended for further investigation and development in the context of NTBD.

Effect of Formulation Parameters on Enalapril Maleate Mucoadhesive Buccal Tablet Using Quality by Design (QbD) Approach.

The buccal route has great prospects and possible benefits for the administration of drugs systemically. The present study involves designing, developing and optimising the buccal tablet formulation of Enalapril Maleate (EM) by using the QbD approach. We prepared the EM buccal tablets using the dry granulation method. In the QTPP profile, the CQAs for EM buccal tablets are Mucoadhesive strength, swelling index and drug release (dependent variables); the CMAs identified for EM buccal tablets were Carbopol 934P, HPMC-K100M and chitosan (independent variables). Diluent quantity, blending time and compression force were selected as CPPs; the Box-Behnkentdesign was used to evaluate the relationship between the CMAs and CPPs. Based on the DoE, the composition of the optimised formulation of EM BT-18 consists of 20mg of EM, 15 mg of carbopol 934p, 17 mg of HPMC-K100M, 10mg of chitosan, 30 mg of PVP K-30, 1 mg of magnesium stearate, 16 mg of Mannitol, 1 mg of aspartame, and 50 mg of Ethyl cellulose. The optimised formulation of EM BT 18 was found to have a Mucoadhesive strength of 24.32±0.30g. The swelling index was 90.74±0.25% and drug release was sustained up to 10 hours 98.4±3.62% compared to the marketed product, whose release was up to 8 hours. We attempted to design a buccal tablet of Enalapril Maleate for sustained drug release in the treatment of hypertension. Patients who cannot take oral medication due to trauma or unconscious conditions could receive the formulation. Development of a newly P.ceutical product is very time-consuming, extremely costly and high-risk, with very little chance of a successful outcome. Hence, this study showed EM tablets are already available on the market but we have chosen a buccal drug delivery system using a novel approach using QbD tools to target the quality of the product accurately.

Mucoadhesive Microspheres: A Promising Delivery System for Helicobacter Pylori (H. pylori) Treatment.

A major worldwide health problem, Helicobacter Pylori (H. pylori) infection is associated with a number of gastrointestinal disorders, such as gastric cancer and peptic ulcers. The shortcomings of traditional treatment plans often include adverse effects, low patient compliance, and the emergence of antibiotic resistance. Investigating different delivery methods is thus necessary to improve the effectiveness of treatment. Mucoadhesive microspheres show promise as a method for delivering anti H. pylori drugs in a targeted and sustained manner. With their ability to stick to the stomach mucosa, these microspheres increase the local concentration of the medication and guarantee a more thorough removal of the pathogen. The potential of Mucoadhesive microspheres in the management of H. pylori infection is examined in this review. We explore the properties and benefits of Mucoadhesive polymers, the production techniques for microspheres, and the variables affecting their functionality. To provide a thorough grasp of this delivery system, a variety of drug-loading strategies, release mechanisms, and in vitro and in vivo assessment methodologies are covered. The potential of Mucoadhesive microspheres to overcome the drawbacks of traditional therapy is shown by highlighting recent developments in their formulation and their therapeutic consequences. Mucoadhesive microspheres constitute an important advancement in the treatment of Helicobacter pylori because they guarantee a regulated release of antibiotics and improve medication absorption at the site of infection. In order to fully appreciate the advantages of this novel delivery method, further study is necessary. Future research paths and the difficulties in the clinical translation of this technology are also discussed.

Permeability of triamcinolone acetonide, released from mucoadhesive films, through a buccal mucosa-mimetic barrier: Permeapad™.

OBJECTIVES: The permeability of triamcinolone acetonide (TA), from bilayer mucoadhesive buccal films, through a biomimetic membrane, Permeapad™, was investigated employing Franz diffusion cell. The delivery systems composition and ethyl cellulose (EC) backing layer, on drug permeability, were assessed. METHODS: Three TA-loaded films were tested; hydroxypropyl methylcellulose (HPMC K4M; bilayer [F1] and monolayer), HPMC K4M/Polyvinylpyrrolidone (PVP): 90/10 [F2], and HPMC K15M film [F3]. All films contained propylene glycol (PG-plasticiser). TA solution alone was used as a control. TA permeability via a Permeapad™ barrier, simulating buccal mucosa, was assessed over 8 h using a Franz diffusion cell. TA permeated into the receptor compartment, released in the donor compartment, and located on/within the Permeapad™ barrier were analysed using UV-spectrophotometer. RESULTS: 45.7 % drug retention within the Permeapad™ barrier was delivered from F1 (highest). F1, F2, and F3 significantly improved the TA's permeability through Permeapad™, compared to TA solution alone (e.g., 8.5 % TA-solution, 21.5 %-F1), attributed to the synergy effect of HPMC and propylene glycol acting as penetration enhancers. F1 displayed a significant increase in drug permeability (receptor compartment; 21.5 %) compared to F3 (17.0 %). PVP significantly enhanced drug permeability (27.5 %). Impermeable EC backing layer controlled unidirectional drug release and reduced drug loss into the donor compartment (e.g., ∼28 % for monolayer film to ∼10 % for bilayer film, F1). SIGNIFICANCE: The mucoadhesive films demonstrated improved TA permeability via Permeapad™. The findings suggest that these bilayer mucoadhesive films, particularly F1, hold promise for the effective topical treatment of oral mucosa disorders, such as recurrent aphthous stomatitis and oral lichen planus.

Adhesive Antibacterial Moisturizing Nanostructured Skin Patch for Sustainable Development of Atopic Dermatitis Treatment in Humans.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex etiology that lacks effective treatment. The therapeutic goals include alleviating symptoms, such as moisturizing and applying antibacterial and anti-inflammatory medications. Hence, there is an urgent need to develop a patch that effectively alleviates most of the AD symptoms. In this study, we employed a "green" cross-linking approach of poly(vinyl alcohol) (PVA) using glycerol, and we combined it with polyacrylonitrile (PAN) to fabricate core-shell (CS) nanofibers through electrospinning. Our designed structure offers multiple benefits as the core ensures controlled drug release and increases the strength of the patch, while the shell provides skin moisturization and exudate absorption. The efficient PVA cross-linking method facilitates the inclusion of sensitive molecules such as fermented oils. In vitro studies demonstrate the patches' exceptional biocompatibility and efficacy in minimizing cell ingrowth into the CS structure containing argan oil, a property highly desirable for easy removal of the patch. Histological examinations conducted on an ex vivo model showed the nonirritant properties of developed patches. Furthermore, the eradication of Staphylococcus aureus bacteria confirms the potential use of CS nanofibers loaded with argan oil or norfloxacin, separately, as an antibacterial patch for infected AD wounds. In vivo patch application studies on patients, including one with AD, demonstrated ideal patches' moisturizing effect. This innovative approach shows significant promise in enhancing life quality for AD sufferers by improving skin hydration and avoiding infections.

Mucoadhesive Mesalamine Prodrug Nanoassemblies to Target Intestinal Macrophages for the Treatment of Inflammatory Bowel Disease.

While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine's pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect. This retention enables the efficient uptake by intestinal pro-inflammatory macrophages expressing high cathepsin B, triggering a burst release of the 5-ASA. This cascade fosters the polarization toward an M2 macrophage phenotype, diminishes inflammatory responses, and simultaneously facilitates the delivery of active agents to adjacent epithelial cells. Therefore, the nanoassemblies show outstanding therapeutic efficacy in inhibiting local inflammation and contribute to suppressing systemic inflammation by restoring damaged intestinal barriers. Collectively, this study highlights the promising role of the prodrug nanoassemblies in enhancing targeted drug delivery, potentially broadening the use of mesalamine in managing IBD.