Search Results (785)

Three-dimensional (3D) printing has emerged as a versatile platform in pharmaceutical sciences, enabling fabrication of personalized dosage forms with controlled drug release and tailored properties using printable hydrogel bioinks. This study aimed to develop mucoadhesive hydrogel buccal films for cannabinoid delivery using extrusion-based 3D bioprinting. The films incorporated cannabidiol (CBD) and tetrahydrocannabinol (THC) as cyclodextrin inclusion complexes with HPMC or Carbopol as mucoadhesive hydrogel-forming polymers, while terpenes were evaluated as permeation enhancers. Terpenes including 1,8-cineole, d-limonene, α-pinene, and L-menthol were investigated individually and in combinations to assess their ability to enhance buccal cannabinoid permeation. Hydrogel bioinks were prepared and characterized for viscosity, pH, and drug content prior to printing under optimized conditions. The printed films were evaluated for mechanical properties, swelling behaviour, mucoadhesion, in vitro drug release, and ex vivo buccal mucosal penetration. Ex vivo penetration studies demonstrated that combinations of natural terpenes significantly improved CBD penetration compared with individual terpenes and the synthetic enhancer Azone. HPMC-based hydrogel films exhibited superior mechanical strength, cohesive gel matrices, and sustained non-Fickian cannabinoid release, while enhancing transmucosal penetration compared with unformulated drugs. Carbopol-based films showed higher mucoadhesion but weaker mechanical properties and faster erosion-driven release. These findings demonstrate the potential of 3D-printed mucoadhesive hydrogel films as gel-based systems for transmucosal cannabinoid delivery. Full article

Background/Objectives: This investigation aims to assess the potential for repurposing nitazoxanide (NIT) as a treatment for COVID-19. NIT was loaded into terpene-enriched chondrosomes (TECs) to assess its anti-hCoV-19 activity through pulmonary delivery. Methods: NIT-TECs were then fabricated utilizing the ethanol injection method. Using a D-optimal design, the effects of factors on entrapment efficiency (EE%), particle size (PS), and zeta potential (ZP) were determined, and the optimal formulation was selected. Results: The optimum TEC exhibited an EE% of 98.87 ± 0.69, a PS of 129.43 ± 5.43 nm, a polydispersity index (PDI) of 0.433 ± 0.022, and a ZP of −25.99 ± 0.99 mV. The optimum TEC was lyophilized to attain a dry powder. Further, the differential scanning calorimetry test confirmed that NIT was transformed from crystalline to amorphous form inside the optimum TEC. In addition, the mucoadhesion test confirmed the ability of the optimum TECs to adhere to pulmonary tissues. Additionally, NIT binding to the active site of SARS-CoV-2 enzymes was investigated using in silico analysis. When compared to NIT, the aerodynamic characteristics of the lyophilized optimum TECs employing the cascade impactor showed superior residence in the lungs. Conclusions: These findings suggest that loading NIT into TECs enhanced its antiviral activity, as indicated by the in vitro cytotoxicity study. Overall, the results point to NIT-loaded TECs as a potentially effective pulmonary delivery system for COVID-19 treatment. Full article

Background/Objectives: Rebamipide is a gastroprotective agent with poor aqueous solubility and rapid gastrointestinal clearance, leading to reduced therapeutic efficiency. This study aimed to enhance the solubility, mucoadhesion, and sustained oral delivery of Rebamipide through the development of a deep eutectic mixture (DEM)-based bioadhesive controlled-release granule formulation. Methods: In silico hydrogen-bonding interactions between Rebamipide, malonic acid, and urea were analyzed using CCDC tools. A thermodynamically stable DEM (1:3:1) was prepared and incorporated into bioadhesive granules using chitosan and HPMC. Physicochemical characterization was conducted using FTIR, DSC, TGA, and PXRD. Solubility, in vitro dissolution, ex vivo mucoadhesion (sheep gastric mucosa), and in vivo gastric retention (BaSO₄-loaded granules in rats) were evaluated. Results: The optimized DEM significantly enhanced Rebamipide solubility (10.08 mg/mL vs. 0.045 mg/mL). Solid-state analyses confirmed hydrogen-bond formation and reduced crystallinity. DEM granules exhibited sustained drug release over 24 h (99.7 ± 0.8%) with improved dissolution efficiency compared to the marketed tablet (Mucosta®, 100 mg; T₅₀%: 5.03 h vs. 0.82 h). Kinetic modeling indicated non-Fickian anomalous transport (n = 0.47). The bioadhesive force of DEM granules (0.29 ± 0.02 N) was significantly higher than that of the pure drug and physical mixture. In vivo radiographic studies confirmed prolonged gastric retention. Conclusions: The DEM-based bioadhesive granule system effectively improves solubility, dissolution rate, mucoadhesion, and gastric retention of Rebamipide. This approach represents a promising platform for once-daily gastroretentive oral delivery, pending further pharmacokinetic evaluation. Full article

The study aimed to develop a mucoadhesive thermosensitive buccal gel capable of forming an artificial clot after application in the extraction socket and providing prolonged release for metronidazole (MZ) and ibuprofen (IB). The critical quality attributes of the product were systematically evaluated using Ishikawa (cause–effect) diagrams as a risk assessment tool, considering the factors related to the formulation, process, and methodology. Subsequently, Failure Mode and Effects Analysis (FMEA) was used to identify the critical parameters of the formulation and process characterized by a high probability of occurrence and a significant impact on product performance. The influence of qualitative and quantitative formulation variables was further investigated using two experimental designs, applied for both screening and optimization purposes. The rheological, adhesion, and in vitro release properties of the drugs were studied, and the optimized formulation for these characteristics contains Poloxamer 407 20.99% and HPMC K100M:K4M 1:1, 0.74%. The release of MZ and IB was prolonged over 8 h and followed Peppas’s kinetics. The optimized formula had an appropriate pH and an acceptable ex vivo mucoadhesion time. Stability studies revealed the preservation of mechanical properties and a recovery coefficient for MZ and IB of over 90%, after 12 months of storage. The optimized formula may be a potential candidate for the prevention of alveolar osteitis. Full article

Cinnamomum zeylanicum (C. zeylanicum) is rich in bioactives, such as cinnamaldehyde and phenols, which are susceptible to thermal degradation, volatilisation, and oxidative deterioration during processing and storage, thereby reducing chemical stability and limiting bioavailability. Encapsulation using lecithin and chitosan-based systems mitigates these instabilities by forming a protective barrier against oxygen, light, and heat while enhancing structural stability. In this study, freeze-dried extracts of C. zeylanicum were encapsulated into lecithin-based primary liposomes (PL) and chitosan-coated secondary liposomes (CH/L). The coating of liposomes with chitosan improves the liposome stability, mucoadhesion, and provides protection in the gastric pH while facilitating electrostatic bonding with the biological membrane. The high compatibility and low toxicity of chitosan also make it a suitable carrier in food and nutraceutical applications. The formed liposomes were characterised for particle size, polydispersity index, zeta potential, encapsulation efficiency (EE), and storage stability over 8 weeks. CH/L showed superior EE (89.027%) compared to the PL (84.154%; p < 0.05). The particle size, polydispersity index, and zeta potential of the cinnamon-loaded lecithin-based primary liposome (CZ-PL) upon formation were 161.93 nm, 0.13, and −37.597 mV. In comparison, those of the cinnamon-loaded chitosan-coated liposomes (CZ-CH/L) were 591.7 nm, 0.27, and +28.17 mV. The particle size of CZ-PL and CZ-CH/L was 175.90 and 588.60 nm after 8 weeks of storage. The TEM confirmed the spherical morphology of the liposomes. The differential scanning calorimetry analysis demonstrated the disappearance of the characteristic cinnamon melting peak and shifts in liposomal transition temperatures, confirming successful encapsulation. FTIR analysis showed reduction or disappearance of characteristic cinnamon fingerprint peaks and slight band shifts, indicating successful encapsulation and non-covalent interactions, including hydrogen bonding and electrostatic effects, within the liposomal systems. These findings imply that lecithin-based and chitosan-coated liposomes could be employed to successfully carry C. zeylanicum bioactives. Full article

Background/Objectives: Enteric drug forms are developed to delay drug release to avoid drug degradation in the acidic environment of the stomach or to prevent irritation of the stomach mucosa. The bioavailability of posaconazole (POS) after oral administration depends on stomach pH and food intake. Delayed-release tablets and unmodified oral suspension are the POS formulations currently available on the market. The oral suspension formulation is characterized by highly variable bioavailability, which may significantly affect therapy effectiveness. Methods: In this study, multi-unit drug forms with delayed and sustained POS release were designed. Polymeric microparticles consisting of sodium alginate (ALG), methacrylic acid–ethyl acrylate copolymer (EUD), or both, were prepared using the spray-drying technique. The formulations that met the pharmacopoeia enteric release standards in the in vitro dissolution test were subjected to further in vitro evaluation via swelling and mucoadhesion assays, an antifungal activity test, attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR), and thermal analysis. Results: It was shown that EUD formulations at concentrations of 5% and 6% provided enteric release, whereas ALG at 1.5% concentration exhibited a sustained, although not delayed, POS release profile. The optimal blended formulations (EAP15–EAP18), comprising 4% EUD with 1.5–2.0% ALG and either 1% or 4% POS, met the pharmacopoeia criteria for enteric dosage forms. Furthermore, these blends demonstrated the most favorable sustained-release profiles in the buffer phase, ranging from 2 to 3 h. The microparticles exhibited beneficial swelling and mucoadhesive properties, which are essential for prolonging contact with the intestinal mucosa; combined with antifungal properties. Conclusions: Obtained carrier may provide a promising preliminary basis for developing a multi-unit, sustained-release enteric dosage form for POS and future in vivo investigations. Full article

Sulfated polysaccharides, carrageenans (CRGs) derived from Chondrus armatus, were used as mucoadhesive matrices for incorporating the antiviral drug acyclovir (ACV). Through IR spectroscopy and quantum-chemical calculations, it was demonstrated that CRGs interact with ACV, forming complexes via intermolecular hydrogen bonding and coordination interactions, with an enthalpy of approximately 15–20 kcal/mol. The monomodal ζ-potential distribution observed in the CRG/ACV mixture confirmed the successful formation of this complex. The antiviral efficacy of the CRG/ACV complex was evaluated during the early stages of herpes simple virus (HSV-1) infection, focusing on its ability to inhibit the cytopathic effects of the virus on host cells. Notably, CRGs enhanced antiviral activity by allowing a reduction in the ACV dosage. Unlike ACV alone, the CRG complex exhibited a prophylactic effect, with therapeutic efficacy comparable to that of ACV. When incorporated into liposomes, the CRG/ACV complex displayed excellent mucoadhesive properties. This liposomal formulation demonstrated notable antiviral activity against infected cells with selective index (SI) 344 and a heightened prophylactic effect (SI 128) compared to the complex alone. Overall, these new antiviral compounds show promise in selectively inhibiting viral adsorption and replication processes without adversely affecting the host organism. Full article

Background/Objectives: Compounded vaginal creams are widely used for conditions such as hormone replacement therapy, vaginal dryness, low libido, vaginal infections, etc. Recent research highlights the potential of using anhydrous bases to extend shelf life, particularly when combined with self-emulsifying and mucoadhesive properties that improve mucosal retention and enhance drug bioavailability. This study provides in vitro and ex vivo evaluation of an anhydrous vaginal base. Methods: Key quality indicators such as irritation potential, leakage potential, pH compatibility, mucoadhesion, and self-emulsification were assessed using the chorioallantoic membrane Hen’s Egg Test, MTT assay, texture analysis, and fluorescence microscopy. Results: The anhydrous vaginal base demonstrated high cell viability (>78%) and non-irritant potential (IS = 2.5) in in vitro assays. It maintained physiological vaginal pH (4.56 ± 0.05), showed strong mucoadhesive properties comparable to commercial products, and exhibited minimal leakage. Ex vivo studies confirmed its prolonged retention on vaginal tissues. The anhydrous vaginal base formed stable emulsions upon contact with vaginal fluid simulant, effectively distributing both lipophilic and hydrophilic compounds. Conclusions: Compared to water-containing bases, an anhydrous vaginal base shows advantages: longer retention time and lower leakage; adaptability to varying vaginal fluid levels; and efficient dispersion of both hydrophilic and lipophilic active pharmaceutical ingredients. These features support its potential use in compounded vaginal products, minimizing stability risks and enhancing patient compliance and therapeutic outcomes. Full article

Background/Objectives: Oral diseases remain among the most prevalent noncommunicable conditions worldwide, with biofilm-driven dysbiosis playing a central role in dental caries, gingivitis, periodontitis, and oral candidiasis. Curcumin has attracted considerable interest because of its anti-inflammatory, antioxidant, antimicrobial, and regenerative properties. However, its clinical use remains limited by poor water solubility, chemical instability, rapid metabolism, and low bioavailability. This review aimed to provide a comprehensive analysis of curcumin-based nanoformulations for oral health applications, with emphasis on their mechanistic actions, antibiofilm activity, and translational relevance. Methods: This review examined representative nanocarrier systems developed for curcumin delivery in oral health. These included polymeric nanoparticles, nanomicelles and nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers, nanogels, hydrogels, mucoadhesive films, and metallic or hybrid nanosystems. The analysis focused on molecular mechanisms of action, antimicrobial and antibiofilm effects against major oral pathogens, and key translational challenges. Results/Findings: Across the reviewed studies, nanoformulations consistently improved curcumin solubility, stability, tissue penetration, mucosal retention, and controlled release. Mechanistically, they enhanced anti-inflammatory activity through inhibition of nuclear factor kappa B (NF-κB), strengthened antioxidant defenses via the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) axis, supported tissue repair and osteogenic responses, disrupted oral biofilms, and modulated local immune responses. Antimicrobial activity was reported against Streptococcus mutans, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Candida albicans, with reduced exopolysaccharide production, impaired adhesion, and improved biofilm penetration. Conclusions: Curcumin-based nanoformulations represent promising adjunctive platforms for oral healthcare. However, their clinical translation still requires improved stability in the oral-environment standardized manufacturing and characterization, rigorous safety evaluation, and well-designed controlled clinical studies. Full article

Purpose: The objective of this study was to engineer and optimize a mucoadhesive, positively charged stearylamine-enriched liposomal platform, termed Aminosomes, to circumvent the biophysical barriers limiting the ocular bioavailability of Brimonidine Tartrate (BT), an alpha-2 adrenergic receptor agonist for glaucoma management. Methods: Aminosomes were synthesized using a tailored ethanol injection technique and optimized via a 3² × 2¹ full factorial design. Molecular integrity and crystallinity were assessed using Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The mucoadhesive potential was validated through a mucin interaction assay based on zeta potential shifts. In vitro release kinetics were evaluated using the dialysis membrane diffusion technique, while the therapeutic potential and ocular safety were validated through in vivo pharmacodynamic profiling of intraocular pressure (IOP) reduction, alongside comprehensive biocompatibility assessments via Draize irritancy protocol and histopathological examination. Results: The optimized Aminosomes exhibited nanometric dimensions, monodisperse size distribution, robust positive surface charge, and superior drug loading. FTIR and XRD analyses confirmed the chemical compatibility of the formulation components, as well as the successful encapsulation of BT and its transition to an amorphous state within the lipidic matrix. The mucoadhesion test demonstrated a high binding affinity for mucin. The in vitro release profile demonstrated a sustained-release pattern (78.8% over 12 h). Non-compartmental pharmacodynamic analysis of IOP-reduction data revealed a 2.8-fold increase in AUC_0–24h, 3.5-fold extension in t_1/2, and 5.2-fold prolongation in mean residence time (MRT) relative to the standard solution. Conclusions: The optimized Aminosomes demonstrated superior mucoadhesive anchoring, enhanced and sustained therapeutic flux without inducing ocular toxicity, offering a robust strategy for enhancing the pharmacodynamics of BT. Full article

The study presents novel photocrosslinked hydrogels based on methacrylated chitosan and methacrylated gelatin/allyl-modified gelatin and compares their properties as drug delivery systems in wound healing applications. The polymers were selected due to their biocompatible, mucoadhesive, cell-interactive properties and flexibility in adjusting their structure, making them suitable candidates for applications that require tissue repair. A range of hydrogel formulations was obtained by modulating the ratio of modified chitosan to two distinct modified gelatins, with photocrosslinking performed using Irgacure 2959 as the photoinitiator. FT-IR analysis, SEM data, and swelling and mechanical properties confirmed the 3D networking and the compatibility between the hydrogel components. Allylic gelatin-based hydrogels present larger pores and a stronger pH-responsive swelling behaviour compared to methacrylated gelatin-based samples, reflecting the higher flexibility of allylic gelatin networks. The hydrogels release bacitracin during the first six hours, with a release profile that follows a non-Fickian diffusion mechanism. Cytocompatibility and wound healing potential were tested in the presence of human and mouse fibroblasts, cells with a pivotal role in the wound healing process. All formulated hydrogels exhibit antioxidant capacity and protein stabilization properties, which are attributed to the presence of chitosan in their composition. The cytocompatibility, in vitro wound healing, and biological properties of the obtained hydrogels, as well as the drug release results, confirm their suitability in wound healing applications. Full article

Periodontitis is a chronic inflammatory disease marked by the progressive destruction of periodontal tissues, where conventional therapies often fail to maintain adequate drug levels at the target site. This study reports the development and characterization of a thermosensitive gel containing nanostructured lipid carriers (NLC) for controlled local periodontal delivery. Apigenin (AP)-loaded NLC were prepared using AP as active agent and clove essential oil (CEO) as liquid lipid subsequently incorporated into Poloxamer 407 (5–15% w/w) hydrogels. The formulations were evaluated in relation to particle size, morphology, thermal and rheological behavior, mucoadhesion, in vitro release, antibacterial activity, and stability. Optimized nanoscale NLC showed a high entrapment efficiency, and uniform morphology. Raman analysis confirmed successful AP incorporation and homogeneous distribution in the gel without incompatibility. NLC-loaded gels exhibited sol–gel transition at physiological temperature with improved viscoelasticity and enhanced mucoadhesion. The drug release was sustained for 48 h and followed the Korsmeyer–Peppas model, indicating diffusion-based and anomalous transport. The antibacterial assessment demonstrated the pronounced inhibitory activity of the NLC formulations against key periodontal pathogens, with the formulation-dependent modulation of antimicrobial efficacy observed following the gel incorporation. Stability studies showed preserved nanoparticle structure and uniform dispersion. Overall, the thermoresponsive NLC-hydrogel system offers a promising strategy for prolonged, localized periodontal therapy. Full article

Oral squamous cell carcinoma (OSCC) therapy frequently produces acute and chronic injury to the oral mucosa, including surgical lining defects and radiochemotherapy-associated oral mucositis (OM). Beyond pain and ulceration, these injuries compromise nutrition, speech, oral hygiene, and feasibility of dental/implant rehabilitation, and may disrupt oncologic treatment delivery. The oral cavity imposes stringent constraints on regenerative biomaterials—continuous salivary flow, high microbial load, and repeated mechanical shear—such that clinical success depends on reliable mucoadhesion/wet adhesion, barrier function, mechanical compliance, and safe, spatially confined bioactivity. This PRISMA-informed evidence-mapped structured narrative review provides an evidence map and structured qualitative synthesis of hydrogel and scaffold platforms relevant to post-OSCC care, spanning clinically used mucoadhesive barrier formulations through emerging wet-adhesive multifunctional patches, acellular matrices, and tissue-engineered oral mucosa (TEOM) constructs. Clinically, the strongest evidence base remains barrier-forming gels and liquids that reduce OM pain and improve oral function during active therapy, establishing performance benchmarks for intraoral retention and patient-reported benefit. Preclinical studies are rapidly expanding toward multifunctional designs that integrate antimicrobial, anti-inflammatory, pro-epithelialization, and pro-angiogenic cues. However, a pervasive limitation is the inconsistent use of OSCC-relevant models (e.g., irradiated/xerostomic tissue beds), standardized functional endpoints (e.g., oral intake, durability under mastication, and neurosensory outcomes), and explicit oncologic safety evaluation, which severely compromises translational validity. For reconstructive applications, dermal matrices and early TEOM reports suggest feasibility for selected defects, but controlled comparative trials and scalable manufacturing pathways remain limited. Translational priorities include oncologic-by-design bioactivity (time-limited, locally confined cues), clinically anchored outcome reporting, and quality-by-design manufacturing aligned with device/combination/advanced-therapy regulatory requirements. Full article

This review presents a comprehensive analysis of modern thermosensitive polymer systems for in situ systems (ISSs) which are used for targeted drug delivery in situ. The main classes of polymers used to create “smart” hydrogels that undergo a “sol–gel” phase transition in response to a temperature stimulus in the physiological range are considered. Key representatives of thermosensitive matrices are described in detail: synthetic block copolymers (poloxamers, block copolymers of polylactic-co-polyglycolic acid with polyethyleneglycol, etc.) and natural, modified natural, and semi-synthetic polymers (chitosan, including in combination with β-glycerophosphate, xyloglucan, etc.). This paper systematizes the advantages and disadvantages of various thermosensitive systems and highlights the key risks in their pharmaceutical development, including the influence of the nature and concentration of the active pharmaceutical ingredients and excipients on the rheological properties and phase transition temperature. Particular attention is paid to the difference between thermoreversible and irreversible gel-forming systems. Modern in vitro, ex vivo, and in vivo methods for evaluating critical quality parameters of thermosensitive systems, such as gelation temperature and time, gel strength, mucoadhesive properties, and release kinetics, are discussed. The need to develop standardized and biologically relevant methods to improve the reproducibility and success of preclinical studies is emphasized. The review is intended to help researchers to make informed choices about polymer matrices and optimize compositions for successful pharmaceutical development. Full article

Oral mucositis frequently develops during radiotherapy or chemotherapy for head and neck cancer and is characterized by severe pain and impaired eating and speech. It was previously demonstrated that freeze-dried hyaluronic acid (HA) sheets effectively promote the healing of oral mucosal ulcers. This study aimed to optimize the HA sheet formulation by evaluating the effects of HA molecular weight and nicotinamide mononucleotide (NMN) loading on therapeutic efficacy. HA sheets were prepared using HA with four different molecular weights (50, 350, 800, and 2000 kDa), and their therapeutic effects were evaluated in an animal oral ulcer model using 6-week-old male Syrian hamsters. Among the formulations tested, the 800 kDa HA sheet exhibited the greatest healing efficacy, and it showed an excellent balance between buccal retention and the sustained release of NMN for the treatment of oral mucositis. In vitro cytotoxicity assays confirmed that HA, with or without NMN, was non-toxic and suitable for local applications. These findings indicate that HA sheets, particularly those composed of 800 kDa HA, may represent a promising and biocompatible mucoadhesive material for the delivery of NMN and the local treatment of oral mucositis associated with head and neck cancer. Full article