Search Results (40)

Background: Local anesthesia is essential for most dental procedures, but its parenteral administration is often painful. Topical anesthetics are commonly used to minimize local anesthesia pain; however, commercial formulations fail to fully prevent the discomfort of local anesthetic injection. Methods: We developed and characterized a novel lidocaine and epinephrine co-loaded liquid crystalline precursor system (LCPS) for topical anesthesia. The formulation was structurally characterized using polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). Rheological behavior was assessed through continuous and oscillatory rheological analyses. Texture profile analysis, in vitro mucoadhesive force evaluation, in vitro drug release and permeation studies, and an in vivo toxicity assay using the chicken chorioallantoic membrane (CAM) model were also conducted. Results: PLM and SAXS confirmed the transition of the LCPS from a microemulsion to a lamellar liquid crystalline structure upon contact with artificial saliva. This transition enhanced formulation consistency by over 100 times and tripled mucoadhesion strength. The LCPS also provided controlled drug release, reducing permeation flow by 93% compared to the commercial formulation. Importantly, the CAM assay indicated that the LCPS exhibited similar toxicity to the commercial product. Conclusions: The developed LCPS demonstrated promising physicochemical and biological properties for topical anesthesia, including enhanced mucoadhesion, controlled drug delivery, and acceptable biocompatibility. These findings support its potential for in vivo application and future clinical use to reduce pain during dental anesthesia procedures. Full article

Background: Captopril (CAP), an angiotensin-converting enzyme inhibitor (ACEI), is widely prescribed for managing hypertension, heart failure, and related conditions. When administered orally, CAP undergoes hepatic metabolism, resulting in a bioavailability of 60–75%. However, to bypass the first-pass metabolism and other limitations of the oral route, mucoadhesive buccal films have gained attention as a promising alternative with several advantages. The aim of this work was the formulation and optimization of chitosan-ascorbate mucoadhesive films for buccal delivery of CAP for the management of a hypertension crisis (10 mg and 20 mg) by employing quality by design (QbD) principles and the design of experiment (DoE) approach. Materials and methods: In the present work, chitosan (CHI) was selected as a film-forming agent due to its permeability-enhancing properties, which could be further improved through salification with ascorbic acid (AA). The polymer films were prepared by the solvent casting method. Results: The optimized CAP-loaded formula showed appropriate in vitro mucoadhesion force (>15 N) and breaking hardness (>14 N). The different CAP-containing films had a high drug content (>95%) with homogeneous drug distribution, thus complying with the requirements of Pharmacopeia. FT-IR and RAMAN spectroscopy analyses demonstrated successful incorporation of the drug, and interaction was observed between the excipients of the films, especially in the form of hydrogen bonds. The dissolution test showed immediate release of the API with a similar release pattern from both concentrations of CAP-loaded films. Conclusions: The properties of the prepared films met the predetermined critical quality attribute requirements. The optimized formula of CHI 1.4%, AA 2.5%, and glycerol 0.3% appears to be a promising buccal drug delivery system for CAP. Full article

Glycerohydrogels based on silicon glycerolate, chitosan (CS) and polyvinyl alcohol (PVA) are widely studied for use in biomedical applications. In line with the general trend of replacing synthetic polymers with natural ones in such compositions, it would be of interest to replace PVA with the polysaccharide glucomannan (GM), as well as to introduce functional additives to impart the desired properties, including gelation time, to the final hydrogel. In this work, a comprehensive study of the preparation conditions and properties of glycerohydrogels based on silicon tetraglycerolate, chitosan hydrochloride (CS·HCl) and GM was carried out. Viscometry was used to assess the conformational state of CS·HCl and GM macromolecules, and their associates in solution before gelation. Gelation was studied using the vessel inversion method. The mucoadhesive and the dermoadhesive properties of the glycerohydrogels obtained were assessed using the tearing off method from the model substrates simulating mucous and dermal tissues. The conformational state of the individual polymers and their mixed associates in solution before gelation was estimated; the intrinsic viscosity and the hydrodynamic radius of the macromolecular coils were calculated. The influence of various factors (addition of ε-aminocaproic and hydrochloric acids, sodium chloride, hydroxide and tetraborate to vary the acidity and ionic strength of the medium, as well as temperature) and the molecular weight of chitosan on the gelation time was studied. The gelation time achieved was less than 2 min, which is promising in practical terms, i.e., for creating liquid plasters. Our best samples are not inferior to the commercial preparation “Metrogyl Denta”^® in terms of tearing force during mucoadhesion and dermoadhesion at short gelation times. Thus, the glycerohydrogels synthesized by us and based on silicon tetraglycerolate, CS·HCl and GM could find usage in new biopharmaceutical and biomedical applications. Full article

It is challenging to deliver therapeutics in the oral environment due to the wet surfaces, the nature of the mucosa and the potential for saliva washout. In this study, the development of a mucoadhesive dimethicone-based oral carrier system for adhesion to the hard tissue and mucosa in the mouth was examined. This study reports the viscosity and mucoadhesion of dimethicone based polymer blends. The viscosity of the materials was measured using a rheometer. The mucoadhesion of these materials was determined as the work of adhesion and peak tack force using the tensile test method with a texture analyzer. Materials were prepared with either calcium and phosphate salts or sodium fluoride as potential therapeutics for promoting remineralization and treating dentin hypersensitivity by mechanical occlusion. Scanning electron microscopy was used to look at mineral deposition on the surface of dental hard tissue after the application of the dimethicone-based formulations. The results of this study confirm the potential for using these dimethicone-based materials as mucoadhesive therapeutic delivery systems in the oral environment. Full article

The aim of this study was to prepare vaginal suppositories with mucoadhesive properties to prolong the action of antifungal component clotrimazole (CLO). This was achieved by preparing vaginal pessaries on a hydrophilic gel base composed of gelatin and gelatin enriched with PEG 400 (in a 1:1 ratio), and then checking the properties of the obtained vaginal drugs. The prepared globules, containing 100 mg of CLO, were characterized in terms of mass and swelling index, organoleptic analysis was also prepared. In addition, a texture analysis and a study of the dissolution of clotrimazole were performed. On the basis of the obtained results, it was concluded that the modification of the composition of the gelatin–glycerin base by the addition of macrogol had a positive effect on the mucoadhesive properties of the globules. In addition, due to the presence of PEG 400, the globules were stiffer. It was also observed that the presence of CLO reduces the value of the force needed for compression during the texture analysis study. Comparing the CLO release profiles of the prepared globules and commercially available clotrimazole tablets, the release profile for the globules was slower than for the tablets, which indicates the possibility of using mucoadhesive globules as a form of a drug that releases the medicinal substance more slowly at the site of administration. Full article

Background/Objectives: Oral diseases causing mucosal lesions are normally treated with local or systemic anti-inflammatory, analgesic and antimicrobial agents. The development of topical formulations, including wound-healing promoters, might speed up the recovery process, improving patients’ quality of life, and reduce the risk of deterioration in health conditions. In this study, a mucoadhesive multilayer film, including a novel biocompatible substance (solubilized eggshell membrane, SESM), was rationally designed. Methods: The SESM preparation procedure was optimized and its biological effects on cell proliferation and inflammation marker gene expression were evaluated in vitro; preformulation studies were conducted to identify the most promising polymers with film-forming properties; then, trilayer films, consisting of an outer layer including chlorhexidine digluconate as a model drug, a supporting layer and a mucoadhesive layer, incorporating SESM, were prepared using the casting method and their mechanical, adhesion and drug release control properties were evaluated. Results: SESM proved to possess a notable wound-healing capacity, inducing a wound closure of 84% in 24 h without inhibiting blood clotting. The films revealed a maximum detachment force from porcine mucosa of approx. 1.7 kPa and maximum in vivo residence time of approx. 200–240 min; finally, they released up to 98% of the loaded drug within 4 h. Conclusions: The formulated trilayer films were found to possess adequate properties, making them potentially suitable for protecting oral lesions and favoring their rapid healing, while releasing antimicrobial substances that might be beneficial in reducing the risk of bacterial infections. Full article

Drug administration by oral delivery is the preferred route, regardless of some remaining challenges, such as short resident time and toxicity issues. One strategy to overcome these barriers is utilizing mucoadhesive vectors that can increase intestinal resident time and systemic uptake. In this study, biomimetic nanoparticles (NPs) were produced from 14 types of edible algae and evaluated for usage as oral DDSs by measuring their size, surface charge, morphology, encapsulation efficiency, mucoadhesion force, and cellular uptake into Caco-2 cells. The NPs composed of algal materials (aNPs) exhibited a spherical morphology with a size range of 126–606 nm and a surface charge of −9 to −38 mV. The mucoadhesive forces tested ex vivo against mice, pigs, and sheep intestines revealed significant variation between algae and animal models. Notably, Arthospira platensis (i.e., Spirulina) NPs (126 ± 2 nm, −38 ± 3 mV) consistently exhibited the highest mucoadhesive forces (up to 3127 ± 272 µN/mm²). Moreover, a correlation was found between high mucoadhesive force and high cellular uptake into Caco-2 cells, further supporting the potential of aNPs by indicating their ability to facilitate drug absorption into the human intestinal epithelium. The results presented herein serve as a proof of concept for the possibility of aNPs as oral drug delivery vehicles. Full article

(1) Background: The study aimed to compare the impact of various natural polymers–sodium alginate, acacia gum, carrageenan, guar gum, xanthan gum, and tragacanth on the formulation and the physical properties of mucoadhesive vaginal tablets containing metronidazole (167 mg/g). (2) Methods: The quality of the tablets prepared by direct compression was evaluated by pharmacopoeia tests (uniformity of mass, resistance to crushing, friability). Mucoadhesion of the tablets was characterized by swelling capacity and mucoadhesive strength, i.e., the force required to detach the tablet from the rabbit mucosa. In vitro drug release was performed by a modified dissolution method in paddle apparatus containing the simulated vaginal fluid (pH 4.5). Scanning electron microscopy observed morphological changes on the swollen tablets’ surface. (3) Results: Pharmacopoeia tests have shown that all prepared tablets met the requirements on quality. The highest mucoadhesive strength was noted in tablets containing guar and xanthan gum. The highest swelling capacity was possessed by tablets containing carrageenan. (4) Conclusions: Summarizing all tests’ results, sodium alginate can be considered the most suitable natural polymer in tablet formulation. The combination of polymers providing higher mucoadhesiveness and at the same time a prolonged release, e.g., xanthan or guar, together with sodium alginate, could also be of interest. Full article

Chitosan succinate is distinguished by its ability to shield the loaded drug from the acidic environment, localize and keep the drug at the colon site, and release the drug over an extended time at basic pH. The current study attempts to develop polyelectrolyte liposomes (PEL), using chitosan and chitosan succinate (CSSC), as a carrier for liposomal-assisted colon target delivery of 5 fluorouracil (5FU). The central composite design was used to obtain an optimized formulation of 5FU-chitosomes. The chitosan-coated liposomes (chitosomes) were prepared by thin lipid film hydration technique. After that, the optimized formulation was coated with CSSC, which has several carboxylic (COOH) groups that produce an anionic charge that interacts with the cation NH2 in chitosan. The prepared 5FU-chitosomes formulations were evaluated for entrapment efficiency % (EE%), particle size, and in vitro drug release. The optimized 5FU-chitosomes formulation was examined for particle size, zeta potential, in vitro release, and mucoadhesive properties in comparison with the equivalent 5FU-liposomes and 5FU-PEL. The prepared 5FU-chitosomes exhibited high EE%, small particle size, low polydispersity index, and prolonged drug release. PEL significantly limited the drug release at acidic pH due to the deprotonation of carboxylate ions in CSSC, which resulted in strong repulsive forces, significant swelling, and prolonged drug release. According to a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, PEL treatment significantly decreased the viability of HT-29 cells. When compared to 5FU-liposome and 5FU-chitosome, the in vivo pharmacokinetics characteristics of 5FU-PEL significantly (p < 0.05) improved. The findings show that PEL enhances 5FU permeability, which permits high drug concentrations to enter cells and inhibits the growth of colon cancer cells. Based on the current research, PEL may be used as a liposomal-assisted colon-specific delivery. Full article

The objective of the current study was to fabricate a thermosensitive in situ gelling system for the ocular delivery of carvedilol-loaded spanlastics (CRV-SPLs). In situ gel formulations were prepared using poloxamer analogs by a cold method and was further laden with carvedilol-loaded spanlastics to boost the precorneal retention of the drug. The gelation capacity, rheological characteristics, muco-adhesion force and in vitro release of various in situ gel formulations (CS-ISGs) were studied. The optimized formula (F2) obtained at 22% w/v poloxamer 407 and 5% w/v poloxamer 188 was found to have good gelation capacity at body temperature with acceptable muco-adhesion properties, appropriate viscosity at 25 °C that would ease its ocular application, and relatively higher viscosity at 37 °C that promoted prolonged ocular residence of the formulation post eye instillation and displayed a sustained in vitro drug release pattern. Ex vivo transcorneal penetration studies through excised rabbit cornea revealed that F2 elicited a remarkable (p ˂ 0.05) improvement in CRV apparent permeation coefficient (P_app = 6.39 × 10⁻⁶ cm/s) compared to plain carvedilol-loaded in situ gel (CRV-ISG; P_app = 2.67 × 10⁻⁶ cm/s). Most importantly, in normal rabbits, the optimized formula (F2) resulted in a sustained intraocular pressure reduction and a significant enhancement in the ocular bioavailability of carvedilol, as manifested by a 2-fold increase in the AUC_0–6h of CRV in the aqueous humor, compared to plain CRV-ISG formulation. To sum up, the developed thermosensitive in situ gelling system might represent a plausible carrier for ophthalmic drug delivery for better management of glaucoma. Full article

Cobalamin (vitamin B₁₂), an essential vitamin with low oral bioavailability, plays a vital role in cellular functions. This research aimed to enhance the absorption of vitamin B₁₂ using sublingual mucoadhesive tablets by increasing the residence time of the drug at the administration site. This research involved the preparation of different 50 mg placebo formulas using different methods. Formulas with disintegration times less than one minute and appropriate physical characteristics were incorporated into 1 mg of cyanocobalamin (S1–S20) using the direct compression method. The tablets obtained were evaluated ex vivo for residence time, and only those remaining for >15 min were included. The final formulas (S5, S8, S11, and S20) were evaluated in several ways, including pre- and post-compression, drug content, mucoadhesive strength, dissolution, and Permeapad^® permeation test employed in the Franz diffusion cell. After conducting the evaluation, formula S11 (Eudragit L100-55) emerged as the most favorable formulation. It exhibited a mucoadhesive residence time of 118.2 ± 2.89 min, required a detachment force of 26 ± 1 g, maintained a drug content of 99.124 ± 0.001699%, and achieved a 76.85% drug release over 22 h, fitting well with the Peppas–Sahlin kinetic model (R²: 0.9949). This suggests that the drug release process encompasses the Fickian and non-Fickian kinetic mechanisms. Furthermore, Eudragit L100-55 demonstrated the highest permeability, boasting a flux value of 6.387 ± 1.860 µg/h/cm²; over 6 h. These findings indicate that including this polymer in the formulation leads to an improved residence time, which positively impacts bioavailability. Full article

The human respiratory syncytial virus (hRSV) is a major cause of serious lower respiratory infections and poses a considerable risk to public health globally. Only a few treatments are currently used to treat RSV infections, and there is no RSV vaccination. Therefore, the need for clinically applicable, affordable, and safe RSV prevention and treatment solutions is urgent. In this study, an ion-activated in situ gelling formulation containing the broad-spectrum antiviral 18β-glycyrrhetinic acid (GA) was developed for its antiviral effect on RSV. In this context, pH, mechanical characteristics, ex vivo mucoadhesive strength, in vitro drug release pattern, sprayability, drug content, and stability were all examined. Rheological characteristics were also tested using in vitro gelation capacity and rheological synergism tests. Finally, the cytotoxic and antiviral activities of the optimized in situ gelling formulation on RSV cultured in the human laryngeal epidermoid carcinoma (HEp-2) cell line were evaluated. In conclusion, the optimized formulation prepared with a combination of 0.5% w/w gellan gum and 0.5% w/w sodium carboxymethylcellulose demonstrated good gelation capacity and sprayability (weight deviation between the first day of the experiment (T0) and the last day of the experiment (T14) was 0.34%), desired rheological synergism (mucoadhesive force (Fb): 9.53 Pa), mechanical characteristics (adhesiveness: 0.300 ± 0.05 mJ), ex vivo bioadhesion force (19.67 ± 1.90 g), drug content uniformity (RSD%: 0.494), and sustained drug release over a period of 6 h (24.56% ± 0.49). The optimized formulation demonstrated strong anti-hRSV activity (simultaneous half maximal effective concentration (EC₅₀) = 0.05 µg/mL; selectivity index (SI) = 306; pre-infection EC₅₀ = 0.154 µg/mL; SI = 100), which was significantly higher than that of ribavirin (EC₅₀ = 4.189 µg/mL; SI = 28) used as a positive control against hRSV, according to the results of the antiviral activity test. In conclusion, this study showed that nasal in situ gelling spray can prevent viral infection and replication by directly inhibiting viral entry or modulating viral replication. Full article

Aim: This study aims to design a novel thiolated κ-carrageenan (κ-CA-SH) and evaluate its potential as an excipient for the design of mucoadhesive drug delivery systems. Methods: Native κ-carrageenan (κ-CA) was thiolated with phosphorous pentasulfide in sulfolane and characterized via ¹H NMR, FTIR, as well as Ellman’s test. Cytotoxicity was assessed via resazurin assay. In vitro release of the model drug, benzydamine hydrochloride, was determined. Tensile and mucosal residence time studies were performed on buccal and small intestinal mucosa. Mucoadhesive features were investigated via rheological studies with freshly isolated porcine mucus. Results: Thiolated κ-CA (κ-CA-SH) with 1213.88 ± 52 µmol/g thiol groups showed no cytotoxicity at a concentration of 1% (m/v) and low cytotoxicity up to 2% (m/v). Benzydamine hydrochloride showed slow release in solution for both polymers. Tensile studies on buccal and intestinal mucosa showed an up to 2.7-fold and 7.7-fold enhancement in the maximum detachment force (MDF) and total work of adhesion (TWA) of κ-CA-SH vs. κ-CA, respectively. The κ-CA-SH exhibited an up to 4.4-fold improved dynamic viscosity with mucus and significantly prolonged residence time on mucosa compared to native κ-CA. Conclusion: Since highly thiolated κ-CA shows a slow release of positively charged active pharmaceutical ingredients and enhanced mucoadhesive properties, it might be a promising excipient for local drug delivery in the oral cavity. Full article

The absorption of drugs with narrow absorption windows in the upper small intestine can be improved with a mucoadhesive drug delivery system such as enteric films. To predict the mucoadhesive behaviour in vivo, suitable in vitro or ex vivo methods can be performed. In this study, the influence of tissue storage and sampling site on the mucoadhesion of polyvinyl alcohol film to human small intestinal mucosa was investigated. Tissue from twelve human subjects was used to determine adhesion using a tensile strength method. Thawing of tissue frozen at −20 °C resulted in a significantly higher work of adhesion (p = 0.0005) when a low contact force was applied for one minute, whereas the maximum detachment force was not affected. When the contact force and time were increased, no differences were found for thawed tissue compared to fresh tissue. No change in adhesion was observed depending on the sampling location. Initial results from a comparison of adhesion to porcine and human mucosa suggest that the tissues are equivalent. Full article

This research was carried out to create a pH-responsive polymeric system for the targeted drug delivery of Diloxanide furoate. It relied on sodium alginate (Na-Alg) and Carbopol 934P as building blocks. Using an aqueous free radical polymerization method, SCH1-SCH12 was created with varying polymer, MAA, and MBA input ratios. Positive outcomes were seen in the swelling and release profiles at higher pH levels. Hydrogel formation, as well as component compatibility, thermal stability, and Diloxanide furoate loading, were all validated by instrumental characterization. A drug loading percentage of 83.56% was determined, with the swelling reaching 743.19%. For the formulation with MBA, the gel fraction was 94.58%. The release of diloxanide furoate increased to 91.77% at neutral pH. The formulation containing Carbopol 934P provided the highest mucoadhesion force (3993.42 dynes/cm²). The created hydrogel has been shown to be biocompatible by toxicological testing of the network. Based on the findings, the created polymeric nexus proved promising for pH-dependent localized and regulated delivery of Diloxanide furoate. Full article