Search Results (116)

Intermittent catheterization mitigates urinary retention for over 300,000 people in the US every year, but can cause microtrauma in the urothelium, compromising its barrier function and increasing the risk of pathogen entry, which may affect user health. To reduce adverse effects, intermittent catheters (ICs) with increased lubricity are used. A common strategy to enhance IC lubricity is to apply a polyvinylpyrrolidone (PVP) coating to ICs; however, this coating can become adhesive upon drying, potentially leading to microtrauma. An alternative approach for lubricity is the migration of integrated amphiphilic surfactant (IAS) within the IC to the surface. The present work examines differences in urethral microtrauma caused by the simulated catheterization of ex vivo porcine urethral tissue using PVP-coated and IAS ICs. Scanning electron microscopy and fluorescence microscopy of the tissue showed the removal of the apical cell layer after contact with the PVP-coated ICs, but not the IAS IC. More extracellular matrices and DNA were observed on the PVP-coated ICs than the IAS IC after tissue contact. Contact angle analysis of the polar and dispersive components of the surface energy demonstrated that the PVP-coated ICs promoted mucoadhesion, while the IAS IC limited mucoadhesion. Overall, the results indicate that IAS ICs cause less microtrauma to urethral tissue than traditional PVP-coated ICs. 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

The application of electrospinning technologies for the preparation of mats based on mucoadhesive polysaccharides, such as chitosan (CS), is an attractive strategy for the development of biopolymeric delivery systems for topical corticosteroids. In this work, an electrospinning technique is described for the preparation of CS-based mats doped with halloysite nanotubes (HNTs) with modified release of clobetasol propionate (CP). The optimized composition of the electrospinning solution was determined: 2.4% solution of CS in 46% acetic acid with addition of PEO (10% of CS mass) and HNTs (5% of CS mass); CP was introduced as an ethanol solution at the rate of 2 mg CP per 1 g of the obtained nonwoven material. The process parameters (the electrospinning voltage of 50–65 kV, the rotation speed of the spinning electrode of 10 min⁻¹, and the distance between the electrodes of 24 cm) were also optimized. The developed technology allowed us to obtain homogeneous nanofiber mats with excellent mechanical properties and biphasic drug release patterns (66% of CP released within 0.5 h and 88% of CP released within 6 h). The obtained nanofiber mats maintained the anti-inflammatory activity of corticosteroid at the level of free CP and showed no cytotoxicity. 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

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

Ocular diseases affecting the anterior and posterior segments of the eye are major causes of global vision impairment. Curcumin, a natural polyphenol, exhibits anti-inflammatory, antioxidant, antibacterial, and neuroprotective properties, making it a promising candidate for ocular therapy. However, its clinical use is hindered by low aqueous solubility, poor bioavailability, and rapid systemic elimination. This review comprehensively highlights advances in curcumin delivery systems aimed at overcoming these challenges. Emerging platforms, including proniosomal gels, transferosomes, and cyclodextrin complexes, have improved solubility, permeability, and ocular retention. Nanoparticle-based carriers, such as hybrid hydrogels and biodegradable nanoparticles, enable sustained release and targeted delivery, supporting treatments for posterior segment diseases like diabetic retinopathy and age-related macular degeneration. For anterior segment conditions, including keratitis and dry eye syndrome, cyclodextrin-based complexes and mucoadhesive systems enhance corneal permeability and drug retention. Mechanistically, curcumin modulates key pathways, such as NF-κB and TLR4, reducing oxidative stress, angiogenesis, and apoptosis. Emerging strategies like photodynamic therapy and neuroprotective approaches broaden their application to eyelid conditions and neuroinflammatory ocular diseases. These advancements address curcumin’s pharmacokinetic limitations, supporting its clinical translation into ophthalmic therapies. This work underscores curcumin’s potential in ocular disease management and advocates clinical trials to validate its safety, efficacy, and therapeutic relevance. Full article

Cellulose nanofibers gained increasing interest in the production of medical devices such as mucoadhesive nanohydrogels due to their ability to retain moisture (high hydrophilicity), flexibility, superior porosity and durability, biodegradability, non-toxicity, and biocompatibility. In this work, we aimed to compare the suitability of selected bacterial and vegetal nanocellulose to form hydrogels for biomedical applications. The vegetal and bacterial cellulose nanofibers were synthesized from brewer’s spent grains (BSG) and kombucha membranes, respectively. Two hydrogels were prepared, one based on the vegetal and the other based on the bacterial cellulose nanofibers (VNC and BNC, respectively). VNC was less opaque and more fluid than BNC. The cytocompatibility and in vitro antioxidant activity of the nanocellulose-based hydrogels were investigated using human gingival fibroblasts (HGF-1, ATCC CRL-2014). The investigation of the hydrogel–mucin interaction revealed that the BNC hydrogel had an approx. 2× higher mucin binding efficiency than the VNC hydrogel at a hydrogel/mucin ratio (mg/mg) = 4. The BNC hydrogel exhibited the highest potential to increase the number of metabolically active viable cells (107.60 ± 0.98% of cytotoxicity negative control) among all culture conditions. VNC reduced the amount of reactive oxygen species (ROS) by about 23% (105.5 ± 2.2% of C−) in comparison with the positive control, whereas the ROS level was slightly higher (120.2 ± 3.9% of C−) following the BNC hydrogel treatment. Neither of the two hydrogels showed antibacterial activity when assessed by the diffusion method. The data suggest that the BNC hydrogel based on nanocellulose from kombucha fermentation could be a better candidate for cytocompatible and mucoadhesive nanoformulations than the VNC hydrogel based on nanocellulose from brewer’s spent grains. The antioxidant and antibacterial activity of BNC and both BNC and VNC, respectively, should be improved. 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

Despite the large number of works on the synthesis of polylactide-co-glycolide (PLGA) nanoparticles (NP) loaded with antituberculosis drugs, the data on the influence of various factors on the final characteristics of the complexes are quite contradictory. In the present study, a comprehensive analysis of the effect of multiple factors, including the molecular weight of PLGA, on the size and stability of nanoparticles, as well as the loading efficiency and release of the antituberculosis drug rifampicin (RIF), was carried out. Emulsification was carried out using different surfactants (polyvinyl alcohol, Tween 80 and Pluronic F127), different aqueous-to-organic phase ratios, and different solvents (dichloromethane, dimethyl sulfoxide, ethyl acetate). In this research, the PLGA nanoemulsion formation process was accompanied by ultrasonic dispersion, at different frequencies and durations of homogenization. The use of the central composite design method made it possible to select optimal conditions for the preparation of PLGA-RIF NPs (particle size 223 ± 2 nm, loading efficiency 67 ± 1%, nanoparticles yield 47 ± 2%). The release of rifampicin from PLGA NPs was studied for the first time using the flow cell method and vertical diffusion method on Franz cells at different pH levels, simulating the gastrointestinal tract. For the purpose of the possible inhalation administration of rifampicin immobilized in PLGA NPs, their mucoadhesion to mucin was studied, and a high degree of adhesion of polymeric nanoparticles to the mucosa was shown (more than 40% within 4 h). In the example of strain H37Rv in vitro, the sensitivity of Mycobacterium tuberculosis to PLGA-RIF NPs was proven by the complete inhibition of their growth. Full article

We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m. Full article

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

Cystinosis is a low-prevalence lysosomal storage disease. The pathomechanism involves abnormal functioning of the cystinosine lysosomal cystine transporter (CTNS), causing intraliposomal accumulation of the amino acid cysteine disulfide, which crystallizes and deposits in several parts of the body. The most common ophthalmic complication of cystinosis is the deposition of “gold dust” cystine crystals on the cornea, which already occurs in infancy and leads to severe photosensitivity and dry eyes as it gradually progresses with age. In the specific treatment of cystinosis, preparations containing cysteamine (CYA) are used. The availability of commercialized eyedrops for the targeted treatment is scarce, and only Cystadrops^® are commercially available with strong limitations. Thus, magistral CYA-containing compounded eyedrops (CYA-CED) could have a key role in patient care; however, a rationally designed comprehensive study on the commercialized and magistral products is still missing. This work aims to build up a comprehensive study about commercialized and magistral CYA eye drops, involving pharmacokinetic and physicochemical characterization (applying mucoadhesivity, rheology test, investigation of drug release, and parallel artificial membrane permeability assays), as well as ex vivo tests, well supported by statistical analysis. Full article

Recent studies have demonstrated that Sirtuin-1 (SIRT-1)-activating molecules exert a protective role in degenerative ocular diseases. However, these molecules hardly reach the back of the eye due to poor solubility in aqueous environments and low bioavailability after topical application on the eye’s surface. Such hindrances, combined with stability issues, call for the need for innovative delivery strategies. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for SIRT-1 delivery can represent a promising approach. The aim of the work was to design and optimize SNEDDS for the ocular delivery of two natural SIRT-1 agonists, resveratrol (RSV) and melatonin (MEL), with potential implications for treating diabetic retinopathy. Pre-formulation studies were performed by a Design of Experiment (DoE) approach to construct the ternary phase diagram. The optimization phase was carried out using Response Surface Methodology (RSM). Four types of SNEDDS consisting of different surfactants (Tween^® 80, Tween^® 20, Solutol^® HS15, and Cremophor^® EL) were optimized to achieve the best physico-chemical parameters for ocular application. Stability tests indicated that SNEDDS produced with Tween^® 80 was the formulation that best preserved the stability of molecules, and so it was, therefore, selected for further technological studies. The optimized formulation was prepared with Capryol^® PGMC, Tween^® 80, and Transcutol^® P and loaded with RSV or MEL. The SNEDDS were evaluated for other parameters, such as the mean size (found to be ˂50 nm), size homogeneity (PDI < 0.2), emulsion time (around 40 s), transparency, drug content (>90%), mucoadhesion strength, in vitro drug release, pH and osmolarity, stability to dilution, and cloud point. Finally, an in vitro evaluation was performed on a rabbit corneal epithelial cell line (SIRC) to assess their cytocompatibility. The overall results suggest that SNEDDS can be used as promising nanocarriers for the ocular drug delivery of RSV and MEL. Full article

The purpose of this work was to investigate the feasibility of a novel ophthalmic formulation of amphotericin B-encapsulated silk fibroin nanoparticles incorporated in situ hydrogel (AmB-FNPs ISG) for fungal keratitis (FK) treatment. AmB-FNPs ISG composites were successfully developed and have shown optimized physicochemical properties for ocular drug delivery. Antifungal effects against Candida albicans and in vitro ocular irritation using corneal epithelial cells were performed to evaluate the efficacy and safety of the composite formulations. The combined system of AmB-FNPs-ISG exhibited effective antifungal activity and showed significantly less toxicity to HCE cells than commercial AmB. In vitro and ex vivo mucoadhesive tests demonstrated that the combination of silk fibroin nanoparticles with in situ hydrogels could enhance the adhesion ability of the particles on the ocular surface for more than 6 h, which would increase the ocular retention time of AmB and reduce the frequency of administration during the treatment. In addition, AmB-FNP-PEG ISG showed good physical and chemical stability under storage condition for 90 days. These findings indicate that AmB-FNP-PEG ISG has a great potential and be used in mucoadhesive AmB eye drops for FK treatment. Full article

Photodynamic therapy using delta-aminolevulinic acid is considered a promising option in the treatment of oral lichen planus. In the present work, three emulgel compositions prepared from natural polysaccharide gums, tragacanth, xanthan and gellan, were preliminarily tested for oromucosal delivery of delta-aminolevulinic acid. Apart from cytotoxicity studies in two gingival cell lines, the precise goal was to investigate whether the presence of the drug altered the rheological and mucoadhesive behavior of applied gelling agents and to examine how dilution with saliva fluid influenced the retention of the designed emulgels by oromucosal tissue. Ex vivo mucoadhesive studies revealed that a combination of xanthan and gellan gum enhanced carrier retention by buccal tissue even upon dilution with the saliva. In turn, the incorporation of delta-aminolevulinic acid favored interactions with mucosal tissue, particularly formulations comprised of tragacanth. The designed preparations had no significant impact on the cell viability after a 24 h incubation in the tested concentration range. Cytotoxicity studies demonstrated that tragacanth-based and gellan/xanthan-based emulgels might exert a protective effect on the metabolic activity of human gingival fibroblasts and keratinocytes. Overall, the presented data show the potential of designed emulgels as oromucosal platforms for delta-aminolevulinic acid delivery. Full article