Search Results (99)

Background: Oral squamous cell carcinoma (OSCC) is one of the most serious forms of cancer in the world. The opportunities to decrease the mortality rate would lie in the possibility of earlier identification of this pathology, and at the same time, the immediate approach of anticancer therapy. Furthermore, new treatment strategies for OSCC are needed to improve existing therapeutic options. Bioactive compounds found in medicinal plants could be used to support these strategies. It is already known that they have an increased potential for action and a safety profile; therefore, they could improve the therapeutic effect of classical chemotherapeutic agents in combination therapies. Methodology: This research was based on an extensive review of recently published studies in scientific databases (PubMed, Scopus, and Web of Science). The selection criteria were based on experimental protocols investigating molecular mechanisms, synergistic actions with conventional anticancer agents, and novel formulation possibilities (e.g., nanoemulsions and mucoadhesive films) for the targeted delivery of bioactive compounds in OSCC. Particular attention was given to in vitro, in vivo, translational, and clinical studies that have proven therapeutic relevance. Results: Recent discoveries regarding the effect of bioactive compounds in the treatment of oral cancer were analyzed, with a view to integrating them into oncological practice for increasing therapeutic efficacy and reducing the occurrence of adverse reactions and treatment resistance. Conclusions: Significant progress has been achieved in this review, allowing us to appreciate that the valorization of these bioactive compounds is emerging. Full article

Hydroxypropyl methylcellulose (Hypromellose, HPMC) is a well-known excipient used in the pharmaceutical and nutraceutical fields due to its versatile physicochemical properties. HPMC (derived from cellulose and obtained through etherification) varies in polymerization degree and viscosity, factors that both influence its functional applications. Usually, an increased polymerization degree implies a higher viscosity, depending also on the amount of polymer used. Hypromellose plays a crucial role in solid dosage forms, serving as a binder in the case of controlled-release tablets, a film-forming agent in the case of orodispersible films and mucoadhesive films, and a release modifier due to its presence in different polymerization degrees in the case of extended or modified release tablets. However, its compatibility with other excipients and the active ingredient must be carefully evaluated to prevent formulation challenges via several analytical methods such as differential scanned calorimetry (DSC), Fourier Transformed Infrared spectroscopy (FT-IR), X-Ray Particle Diffraction (XRPD), and Scanning Electron Microscopy (SEM). This review explores the physicochemical characteristics, and diverse applications of HPMC, emphasizing its significance in modern drug delivery systems. Full article

Background/Objectives: Non-invasive central nervous system (CNS) therapies are limited by complex mechanisms and the blood–brain barrier, but nasal delivery offers a promising alternative. The study planned to develop a non-invasive in situ intranasal mucoadhesive thermosensitive gel to deliver CNS-active risperidone via nose-to-brain targeting. Risperidone, a second-generation antipsychotic, has shown efficacy in managing both psychotic and mood-related symptoms. The mucoadhesive gel formulations help to prolong the residence time at the nasal absorption site, thereby facilitating the uptake of the drug. Methods: The poloxamer 407 (18.0% w/v), HPMC K100M and K15M (0.3–0.5% w/v), and benzalkonium chloride (0.1% v/v) were used as thermosensitive polymers, a mucoadhesive agent, and a preservative, respectively, for the development of in situ thermosensitive gel. The developed formulations were evaluated for various parameters. Results: The pH, gelation temperature, gelation time, and drug content were found to be 6.20 ± 0.026–6.37 ± 0.015, 34.25 ± 1.10–37.50 ± 1.05 °C, 1.65 ± 0.30–2.50 ± 0.55 min, and 95.58 ± 2.37–98.03 ± 1.68%, respectively. Furthermore, the optimized F3 formulation showed satisfactory gelling capacity (9.52 ± 0.513 h) and an acceptable mucoadhesive strength (1110.65 ± 6.87 dyne/cm²). Diffusion of the drug through the egg membrane depended on the formulation’s viscosity, and the F3 formulation explained the first-order release kinetics, indicating concentration-dependent drug diffusion with n < 0.45 (0.398) value, indicating the Fickian-diffusion (diffusional case I). The pharmacokinetic study was performed with male Wistar albino rats, and the F3 in situ thermosensitive risperidone gel confirmed significantly (p < 0.05) ~5.4 times higher brain AUC_0–∞ when administered intranasally compared to the oral solution. Conclusions: Based on physicochemical, in vitro, and in vivo parameters, it can be concluded that in situ thermosensitive gel is suitable for administration of risperidone through the nasal route and can enhance patient compliance through ease of application and with less repeated administration. Full article

Excessive blood loss is a leading cause of mortality among soldiers and accident victims. The wound healing process typically ranges from three weeks to several months, with disruptions in healing stages potentially prolonging recovery time. Chronic wounds may persist for years, creating a favorable environment for microbial growth. Chitosan, a derivative of chitin—the second most abundant biopolymer in nature—is obtained through deacetylation and exhibits mucoadhesive, analgesic, antioxidant, biodegradable, non-toxic, and biocompatible properties. Due to its hemostatic and regenerative support capabilities, chitosan is widely applied in the food, cosmetic, and agricultural industries; environmental protection; and as a key component in dressings for chronic wound healing. Notably, its antibacterial properties make it a promising candidate for novel biomaterials to replace traditional antibiotics and prevent the emergence of drug-resistant strains. The primary aim of this study was the chemical cross-linking of chitosan with the amino acids L-aspartic and L-glutamic acid in the presence of periclase (magnesium oxide) under microwave radiation conditions. Subsequent research stages involved the analysis of the samples’ physicochemical properties using SEM, FT-IR, XPS, atomic absorption spectrometry, swelling behavior (in water, SBF, and blood), porosity, and density. Biological assessments included biodegradation, cytotoxicity, and antibacterial activity against Escherichia coli and Staphylococcus aureus. The obtained results confirmed the high potential of the newly developed hemostatic agents for effective hemorrhage management under non-sterile conditions. 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

Hydrogel delivery systems are popular dosage forms that have a number of advantages, such as ease of use, painlessness, increased efficiency due to prolongation of rheological, swelling and sorption characteristics, regulation of drug release, and stimulus sensitivity. Particular interest is shown in hydrogels of cellulose ether derivatives due to the possibility of obtaining their modified forms to vary the solubility, the degree of prolonged action, and the release of the active substance, as well as their widespread availability, affordability, and the possibility of sourcing raw materials from different sources. Hydroxypropyl methylcellulose (HPMC, “hypromellose”) is one of the most popular cellulose ethers in the production of medicines as a filler, coating and carrier. Research on hydrogel carriers based on polymer complexes and modified forms of HPMC using acrylic, citric, and lactic acids, PVP, chitosan, Na-CMC, and gelatin is of particular interest, as they provide the necessary rheological and swelling characteristics. There is growing interest in medical transdermal hydrogels, films, capsules, membranes, nanocrystals, and nanofibers based on HPMC with the incorporation of biologically active substances (BASs), especially those of plant origin, as antibacterial, wound-healing, antimicrobial, mucoadhesive, anti-inflammatory, and antioxidant agents. The aim of this article is to review modern research and achievements in the field of hydrogel systems based on cellulose ethers, particularly HPMC, analyzing their properties, methods of production, and prospects for application in medicine and pharmacy. Full article

The oral administration of probiotics is a promising strategy to regulate the host–intestinal flora balance and improve health. Nevertheless, adverse gastrointestinal (GI) conditions affect the activity of free native probiotics. In this study, a novel probiotic encapsulation system based on milk exosomes (mExos) and DSPE-PEG-PBA was developed. mExos acted as a shield to protect probiotics from harsh GI environments, and DSPE-PEG-PBA served as a bridge between mExos and probiotics. The coated probiotics were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and intrinsic fluorescence spectra. The results showed three probiotics (Akkermansia muciniphila (AKK), Bifidobacterium animalis subsp. lactis BB-12 (BB12), and Lactiplantibacillus plantarum Q7 (Q7)) were coated with mExos@DSPE-PEG-PBA, with encapsulation rates of 90.37 ± 0.45%, 84.47 ± 1.22%, and 70.93 ± 2.39%, respectively. This encapsulation not only preserved the growth activity of the probiotics but also provided robust protection against the detrimental effects of acidic pH, bile salts, and digestive enzymes. The encapsulated strains Q7, BB12, and AKK demonstrated survival rates of 80.99 ± 0.41%, 85.28 ± 0.20%, and 94.53 ± 0.26%, respectively, in an in vitro simulated GI environment. The mExos@DSPE-PEG-PBA-encapsulated probiotics exhibited enhanced hydrophobicity and auto-aggregation capacity, accompanied by a significant improvement in mucoadhesive properties, which collectively potentiated their colonization potential within the gastrointestinal tract. These findings substantiate the potential of mExos as an encapsulation platform for probiotics, providing valuable insights into the selection of exosomes as encapsulating agents to enhance probiotic viability and mucoadhesive capacity. Full article

Atorvastatin calcium, an antifungal agent, has the potential to be repositioned/repurposed to combat the increasing antimicrobial resistance. However, one of the most crucial issues in developing atorvastatin calcium-loaded products with a topical antifungal effect is achieving the optimal release and dissolution rates of this statin to produce the desired therapeutic effect. In this paper, we report on the development and pharmaceutical assessment of hydrogels composed of low-molecular-weight chitosan, tragacanth, and xanthan gum/pectin/κ-carrageenan as potential drug carriers for atorvastatin calcium for buccal delivery. Multidirectional analysis of the carriers with regard to their drug-release profiles and mucoadhesive, antimicrobial, and cytotoxic properties was accompanied by an evaluation of the freeze-drying process used to improve the hydrogels’ applicability. Using differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy techniques, the role of lyophilization in enhancing atorvastatin calcium delivery from polyelectrolyte complex-based matrices via drug amorphization was demonstrated. The freeze-dried hydrogels had significantly improved release and dissolution rates for the amorphic statin. Therefore, there is great potential for the use of lyophilization in the design of polyelectrolyte complex-based semi-solids in usable dosage forms for numerous crystalline and poorly water-soluble active substances. Full article

Background/Objectives: Posaconazole is an antifungal agent from triazoles with variable bioavailability. To avoid its irregular absorption caused by gastric conditions and ensure more repeatable pharmacokinetic enabling the maximization of its absorption regardless of food intake without the need to administer multiple doses, can be provided by the technology of enteric drug preparations. The cross-linking of polysaccharide polymers with divalent and trivalent cations enables multi-unit formulations to be obtained that prevent drug absorption in the stomach. Microcapsules, as an example of multi-unit drug dosage forms, provide more predictable gastric emptying, depending on nutritional status, and spread extensively throughout the gastrointestinal tract. Methods: Therefore, the utilization of zinc acetate for the cross-linking of the alginate and pectin mixture was evaluated. The obtained formulations were evaluated for the impact of cross-linking process and pectin’s presence on their pharmaceutical, mucoadhesive, physicochemical and antifungal properties. Results: It was shown that cross-linked microcapsules by zinc acetate provided delayed posaconazole release. Additionally, the cross-linking process with Zn²⁺ ions significantly enhanced antifungal activity against the analyzed Candida strains. It was observed that pectin content in the formulation enhanced the swelling ability in an intestinal condition and increased the mucoadhesive properties of drug-loaded formulations to the intestinal mucosa. Full article

This research aimed to develop mucoadhesive buccal films incorporating nanostructured lipid carriers (NLCs) loaded with triamcinolone acetonide (TN-films). A Box–Behnken design was employed as a systematic approach to optimize the formulation. Key components of the NLCs—spermaceti, soybean oil, and polysorbate 80—were considered independent variables. The NLCs were prepared and size-reduced using a combination of hot homogenization and ultrasonic probe techniques. Films were cast using hydroxypropyl methylcellulose (HPMC) as the film-forming agent. The TN-films were characterized based on weight, thickness, tensile strength, elongation at break, contact angle, and surface free energy. Linear regression showed that spermaceti increased film weight and thickness, while polysorbate 80 decreased them. The mechanical strength of the films was primarily influenced by spermaceti; higher concentrations of spermaceti resulted in decreased film strength. Additionally, all independent variables contributed positively to the lipophilicity of the films. The TN-films were found to sustain drug release via a Fickian diffusion mechanism, exhibiting rapid swelling and favorable mucoadhesive properties. Moreover, the TN-films demonstrated superior drug release and permeation to pastes and films loaded with emulsions. These findings suggest that the TN-films represent a promising and effective approach for the buccal delivery of triamcinolone acetonide. Full article

Many antifungal agents, including isoconazole nitrate (ISN), suffer from low aqueous solubility and inconsistent dissolution kinetics, which limit their therapeutic potential. To address these challenges, this study aimed to enhance the solubility and stability of ISN through the development of inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-β-CD). HP-β-CD inclusion complexes were prepared using a spray-drying technique and characterized through phase-solubility studies, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H-NMR), and differential scanning calorimetry (DSC). The inclusion complex significantly improved ISN solubility, increasing from 0.5088 mg/mL to 3.6550 mg/mL. These complexes were incorporated into a thermosensitive, mucoadhesive in situ gel system using Pluronic^® F127 and hydroxypropyl methylcellulose (HPMC) to optimize vaginal drug delivery. The formulations were evaluated for gelation temperature, viscosity, swelling behavior, and pH, confirming their suitability for vaginal application. Antimicrobial studies demonstrated that the ISN/HP-β-CD gels exhibited superior activity against Candida albicans, C. glabrata, and C. krusei compared to ISN alone. In vitro release studies further revealed sustained drug release following Peppas-Sahlin kinetics, supporting enhanced bioavailability and prolonged therapeutic action. This study demonstrates that the ISN/HP-β-CD-loaded in situ gel system offers a promising and effective approach for improving the solubility, stability, and antifungal efficacy of ISN for the treatment of vaginal infections. Full article

Cilostazol (CIL), a BCS class II antiplatelet aggregation and vasodilator agent, is used for cerebrovascular diseases to minimize blood–brain barrier dysfunction, white matter-lesion formation, and motor deficits. The current work aimed to develop and optimize cilostazol-loaded spanlastics (CIL-SPA) for nose-to-brain delivery to overcome the low solubility and absorption, the first pass-metabolism, and the adverse effects. The optimal CIL-SPA formulation was loaded into Phytagel^® (SPA-PG), Poloxamer-407 (SPA-P407), and chitosan (SPA-CS) gel bases and characterized in terms of colloidal properties, encapsulation efficiency (EE%), mucoadhesive properties, and biopharmaceutical aspects. The developed in situ gelling formulations showed a <300 nm average hydrodynamic diameter, <0.5 polydispersity index, and >|±30| mV zeta potential with a high EE% (>99%). All formulations met the droplet size-distribution criteria of nasal requirements (<200 µm), and all formulations showed adequate mucoadhesion properties. Both the BBB-PAMPA and horizontal permeability study through an artificial membrane revealed that all formulations had higher CIL flux and cumulative permeability at in vitro nose-to-brain conditions compared to the initial CIL. The in vitro drug-release study showed that all formulations released ca. 100% of CIL after 2 h. Therefore, the developed formulations could be promising for improving the low bioavailability of CIL through nose-to-brain delivery. Full article

The study focuses on the development of an in situ gelling dexamethasone (DEX) oromucosal formulation designed for the treatment of aphthous stomatitis. Three series of formulations were prepared; a first series containing DEX suspended, a second series containing DEX and, in addition, mint essential oil (EO), and a third series containing EO and DEX solubilized in propylene glycol (PG). In the composition, polymers in the role of mucoadhesive agent were interchanged (hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), methyl cellulose (MC), carboxymethyl cellulose (CMC), and sodium carboxymethyl cellulose (NaCMC). Specifically, DEX was incorporated at a concentration of 0.1% (w/w) in each formulation. The influence of mint EO and DEX solubilization on the physical properties (pH measurements, rheological analysis, swelling ability, and texture analysis) and in vitro drug release was studied. Key findings revealed that HPMC-based formulation containing mint EO and PG exhibited best swelling properties (700 ± 46% after 5 h), adequate adhesiveness and in vitro drug release (34.7 ± 5.9%). Furthermore, the irritation potential assessed via the hen’s egg test on the chorioallantoic membrane (HET-CAM) demonstrated low irritancy risk. Finally, Fourier-transform infrared spectroscopy (FT-IR) showed no incompatibility between DEX and excipients. Overall, the research highlights the potential of mucoadhesive systems in improving the therapeutic efficacy of oromucosal drug delivery for managing painful oral lesions. Full article

Background/Objectives: Films in the mouth offer a promising alternative drug delivery system for oral administration, with several advantages over traditional oral formulations. Furthermore, their non-invasive nature and easy administration make them conducive to increasing patient compliance. The use of active agents in these films can further improve their drug delivery properties, making them an even more useful drug delivery system. Methods: In this research, carrageenan was used as a polymer, while glycerine was added as a plasticizer, furthermore, lidocaine hydrochloride and diclofenac sodium were used as the active agents. The prepared films were characterized by analytical techniques. Results: The results showed that glycerine reduced the mucoadhesivity and breaking hardness of the films and increasing the temperature made the films brittle. These results are also confirmed by the statistical analysis. Based on the FTIR results, glycerine can be used in films without structural changes. Conclusions: Based on the findings, films prepared from a solution with a concentration of 1.5% carrageenan and 1.5% glycerine at 70 °C are suitable as a drug delivery system for use on the buccal mucosa when combined with active agents. Carrageenan was successfully used as a carrier for two different types of active agents. Full article

Background: Despite extensive research over the decades, cancer therapy is still a great challenge because of the non-specific delivery of chemotherapeutic agents, which could be overcome by limiting the distribution of chemotherapeutic agents toward cancer cells. Objective: To reduce the cytolytic effects against cancer cells, graphene oxide (GO) nanoparticles (NPs) can load anticancer medicines and genetic tools. Methodology: During the current study, folic-acid-conjugated graphene oxide (Fa-GO) hybrid mucoadhesive chitosan (CS)-based hydrogel beads were fabricated through an “ion-gelation process”, which allows for regulated medication release at malignant pH. Results: The fabricated chitosan–alginate (SA-CS) hydrogel beads were examined using surface morphology, optical microscopy, XRD, FTIR, and homogeneity analysis techniques. The size analysis indicated that the size of the Fa-GO was up to 554.2 ± 95.14 nm, whereas the beads were of a micrometer size. The folic acid conjugation was confirmed by NMR. The results showed that the craggy edges of the graphene oxide were successfully encapsulated in a polymeric matrix. The mucoadhesive properties were enhanced with the increase in the CS concentration. The nanohybrid SA-CS beads exhibited good swelling properties, and the drug release was 68.29% at pH 5.6 during a 24 h investigation. The accelerated stability study, according to ICH guidelines, indicated that the hydrogel beads have a shelf-life of more than two years. Conclusions: Based on the achieved results, it can be concluded that this novel gastro-retentive delivery system may be a viable and different way to improve the stomach retention of anticancer agents and enhance their therapeutic effectiveness. Full article