Mucoadhesive delivery systems for oral candidiasis treatment: A systematic review and meta-analysis.

OBJECTIVES: This systematic review and meta-analysis aimed to evaluate the clinical and mycological effectiveness of mucoadhesives as vehicles for drugs or natural products in the treatment of oral candidiasis. MATERIALS AND METHODS: The search for articles was carried out in the Medline/PubMed, SCOPUS, EMBASE, Web of Science, Cochrane Library, and SciELO databases before August 2023. We selected the studies, extracted the data, evaluated the study quality, graded the evidence, performed the risk of bias, and carried out meta-analysis. RESULTS: A total of 389 potentially relevant articles were identified, and 11 studies (1869 participants) met the inclusion criteria of the systematic review. The overall risk of bias was considered low. The most common presentation of mucoadhesives was tablets, with miconazole being the most frequently drug used in the delivery system. Mucoadhesives demonstrated comparable efficacy with topical or systemic antifungal agents, with no significant differences between treatments in terms of clinical (RR = 0.907; 95CI = 0.3-1.297; p = 0.591; I2 = 64.648) or mycological (RR = 0.95; 95CI = 0.667-1.360; p = 0.789; I2 = 73.271) efficacy. CONCLUSIONS: Mucoadhesives may be a suitable alternative to conventional treatments, with the advantage of reducing the frequency of application by up to 5 times and the daily dosage by up to 20 times.

In Vitro and In Vivo Evaluation of Magnetic Floating Dosage Form by Alternating Current Biosusceptometry.

Floating controlled systems seek to extend the gastric retention time (GRT) of solid pharmaceutical forms by sustaining buoyancy in the stomach without affecting gastric emptying rates. This investigation aimed to evaluate a magnetic floating drug delivery system (MFDDS) under diverse physiological conditions (pressure and viscosity) using an Alternating Current Biosusceptometry (ACB) system by conducting assessments in vitro and in vivo. For in vitro experiments, MFDDSs were placed under different pressures (760, 910, and 1060 mmHg) and viscosities (1, 50, 120, and 320 mPa·s) for evaluation of floating lag time (FLT). For in vivo experiments, eight healthy volunteers participated in two phases (fasting and fed) for gastric parameters (GRT, FLT, and OCTT-orocaecal transit time) assessment, employing the ACB system. The results indicated that pressure, viscosity, and FLT were directly proportional in the in vitro assay; in addition, increases in the OCTT (fasting = 241.9 ± 18.7; fed = 300 ± 46.4), GRT (fasting = 139.4 ± 25.3; fed = 190.2 ± 47.7), and FLT (fasting = 73.1 ± 16.9; fed = 107.5 ± 29.8) were detected in vivo. Our study emphasizes that the ACB system is a valuable technique, and it is capable of tracking and imaging MFDDS in in vitro and in vivo experiments.

Lemongrass essential oil micro- and nanoencapsulation for industrial application: Production techniques and potential applications.

Due to its characteristic aroma and diverse therapeutic properties, lemongrass essential oil (LEO) has garnered increased attention in the pharmaceutical, food, and cosmetic industries. However, LEO's volatile nature, low chemical stability, and limited solubility in water limits its applications in the industry. Micro- and nanoencapsulation technologies emerge as a promising solution to overcome these challenges. A systematic methodology involving keyword searches in databases was employed to gather relevant literature on LEO micro- and nanoencapsulation, providing an extensive overview of techniques, processes, encapsulating materials, and possible applications. Beyond established methods, emerging techniques were explored. This review highlights the critical role of encapsulation in enhancing the thermal and chemical stability, applicability, bioavailability, and controlled release of LEO.

Characterization and antifungal activity of chlorhexidine:ß-cyclodextrin inclusion complexes.

Aim: This study aimed to develop, characterize and analyze the antifungal activity of chlorhexidine:ß-cyclodextrin inclusion complexes (Chx:ßCD). Materials & methods: Chx:ßCD were characterized by physicochemical techniques and the susceptibility of nine Candida strains was assessed. The inhibition of Candida albicans biofilm growth was evaluated in a denture material modified with the incorporation of Chx:ßCD. Results: Chx was better complexed in 1:2 molar ratio by freeze-drying. Chx:ßCD presented antifungal activity against all Candida strains. When incorporated into the denture material, Chx:ßCD showed better antifungal activity, as it required about 7.5% of Chx concentration compared with the raw Chx for 14 days. Conclusion: The improved characteristics of Chx:ßCD can result in new formulations to treat oral candidiasis and denture stomatitis.

Many people who wear dentures can get a fungal infection called denture stomatitis. Treating this infection is hard because it often comes back. There are many reasons why it can come back, like not following instructions, taking the wrong amount of medicine or having a bad reaction to the drugs. Using old and poorly fitting dentures and the difficulty to maintain the medicine in the right place can also make it harder to get better. One idea to make treatment easier is to add stronger drugs with fewer side effects to the material used to make dentures. That way, patients would only need to wear dentures with the right amount of medicine for a certain time to treat the infection.

Biopharmaceutical and nanotoxicological aspects of cyclodextrins for non-invasive topical treatments: A critical review.

Cyclodextrins are nanometric cyclic oligosaccharides with amphiphilic characteristics that increase the stability of drugs in pharmaceutical forms and bioavailability, in addition to protecting them against oxidation and UV radiation. Some of their characteristics are low toxicity, biodegradability, and biocompatibility. They are divided into α-, ß-, and γ-cyclodextrins, each with its own particularities. They can undergo surface modifications to improve their performances. Furthermore, their drug inclusion complexes can be made by various methods, including lyophilization, spray drying, magnetic stirring, kneading, and others. Cyclodextrins can solve several problems in drug stability when incorporated into dosage forms (including tablets, gels, films, nanoparticles, and suppositories) and allow better topical biological effects of drugs at administration sites such as skin, eyeballs, and oral, nasal, vaginal, and rectal cavities. However, as they are nanostructured systems and some of them can cause mild toxicity depending on the application site, they must be evaluated for their nanotoxicology and nanosafety aspects. Moreover, there is evidence that they can cause severe ototoxicity, killing cells from the ear canal even when applied by other administration routes. Therefore, they should be avoided in otologic administration and should have their permeation/penetration profiles and the in vivo hearing system integrity evaluated to certify that they will be safe and will not cause hearing loss.

Characterization, Antifungal Evaluation against Candida spp. Strains and Application of Nystatin: ß-cyclodextrin Inclusion Complexes.

BACKGROUND: Nystatin (Nys) is a fungicidal drug commonly prescribed for candidiasis disease in several administration routes. However, Nys is a class IV drug, according to the Biopharmaceutical Classification System, that possesses limited bioavailability and is used for local activity. OBJECTIVE: This study developed and characterized nystatin:ß-cyclodextrin (Nys:ßCD) inclusion complexes and evaluated their activity against Candida spp. METHODS: Complexes were characterized by physicochemical techniques and drug dissolution profiles. The susceptibility of C. albicans, C. krusei, C. parapsilosis, C. glabrata, C. guilliermondii, C. tropicalis, and C. auris was assessed using the broth microdilution method. The applicability of Nys:ßCD inclusion complex was evaluated by incorporating it into a temporary soft material for denture stomatitis treatment. RESULTS: Nys was better complexed in a 1:1 molar ratio by freeze-drying and spray-drying methods. The inclusion complexes show bi-exponential release, an initial burst release followed by a sustained manner, presenting higher dissolution efficiency than raw Nys. The 1:1 freeze-drying Nys:ßCD complex presents antifungal activity against all evaluated Candida strains, showing the maintenance of the drug effectiveness. The inclusion complex incorporated into a tissue conditioner material for denture stomatitis treatment effectively inhibited more than 90% of C. albicans biofilm growth during 7 and 14 days, in a half dose compared to raw Nys. CONCLUSION: This work represents a significant contribution to treating a wide variety of diseases caused by the Candida species, optimizing the drug bioavailability and compliance to the treatment due to improved drug solubility, dissolution, and sustained delivery.

Exploiting Polymeric Films as a Multipurpose Drug Delivery System: a Review.

Polymeric films are drug delivery systems that maintain contact with the delivery tissue and sustain a controlled release of therapeutic molecules. These systems allow a longer time of drug contact with the target site in the case of topical treatments and allow the controlled administration of drugs. They can be manufactured by various methods such as solvent casting, hot melt extrusion, electrospinning, and 3D bioprinting. Furthermore, they can employ various polymers, for example PVP, PVA, cellulose derivatives, chitosan, gelling gum, pectin, and alginate. Its versatility is also applicable to different routes of administration, as it can be administered to the skin, oral mucosa, vaginal canal, and eyeballs. All these factors allow numerous combinations to obtain a better treatment. This review focuses on exploring some possible ways to develop them and some particularities and advantages/disadvantages in each case. It also aims to show the versatility of these systems and the advantages and disadvantages in each case, as they bring the opportunity to develop different medicines to facilitate therapies for the most diverse purposes .

Solid Dispersions Incorporated into PVP Films for the Controlled Release of Trans-Resveratrol: Development, Physicochemical and In Vitro Characterizations and In Vivo Cutaneous Anti-Inflammatory Evaluation.

Trans-resveratrol can promote various dermatological effects. However, its high crystallinity decreases its solubility and bioavailability. Therefore, solid dispersions have been developed to promote its amorphization; even so, they present as powders, making cutaneous controlled drug delivery unfeasible and an alternative necessary for their incorporation into other systems. Thus, polyvinylpyrrolidone (PVP) films were chosen with the aim of developing a controlled delivery system to treat inflammation and bacterial infections associated with atopic dermatitis. Four formulations were developed: two with solid dispersions (and trans-resveratrol) and two as controls. The films presented with uniformity, as well as bioadhesive and good barrier properties. X-ray diffraction showed that trans-resveratrol did not recrystallize. Fourier-transform infrared spectroscopy (FT-IR) and thermal analysis evidenced good chemical compatibilities. The in vitro release assay showed release values from 82.27 ± 2.60 to 92.81 ± 2.50% (being a prolonged release). In the in vitro retention assay, trans-resveratrol was retained in the skin, over 24 h, from 42.88 to 53.28%. They also had low cytotoxicity over fibroblasts. The in vivo assay showed a reduction in inflammation up to 66%. The films also avoided Staphylococcus aureus's growth, which worsens atopic dermatitis. According to the results, the developed system is suitable for drug delivery and capable of simultaneously treating inflammation and infections related to atopic dermatitis.

Antimicrobial dressing of silver sulfadiazine-loaded halloysite/cassava starch-based (bio)nanocomposites.

(Bio)nanocomposites have been studied for biomedical applications, including the treatment of wounds. However, wound infection is one of the main problems of wound care management, and the use of wound dressings with antibacterial agents is essential. This work focused on developing and characterizing silver sulfadiazine-loaded halloysite/cassava starch-based (bio)nanocomposites potentially suitable as antimicrobial dressing. Silver sulfadiazine was complexed inside the halloysite nanotubes lumen, and the drug-loaded nanotubes were incorporated in thermoplastic starch dispersion, forming the (bio)nanocomposites. The silver sulfadiazine-loaded halloysite and the (bio)nanocomposite were characterized by zeta potential, scanning electron microscopy, X-ray diffraction, and infrared spectroscopy. The dressing properties of (bio)nanocomposites (water vapor permeability and mechanical stability) and their antimicrobial efficacy by Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were also evaluated. Physicochemical studies suggested the silver sulfadiazine-loaded halloysite complexation (zeta potential of -38.9 mV) and its interactions with the starch forming the nanocomposites. The silver sulfadiazine-loaded halloysite/starch-based (bio)nanocomposites possessed a homogeneous and organized structure. Also, they had mechanical properties to be used as a dressing (13.73 ± 3.09 MPa and 3.17 ± 1.28% of elongation at break), and its permeability (6.18 ± 0.43 (10-13) g.Pa-1.s-1.m-1) could be able to maintain the environmental moisture at the wound surface. Besides that, the (bio)nanocomposites acted against the studied bacteria, being a potential contact antimicrobial and biodegradable wound dressing. Finally, the developed (bio)nanocomposites are semi-occlusive and good candidates for dry wounds to be widely in vitro and in vivo tested as controlled silver sulfadiazine delivery dressing.

Hesperidin-Loaded Solid Lipid Nanoparticles: Development and Physicochemical Properties Evaluation.

Although nanocarrier systems have been investigated to function as therapeutic delivery agents to specific sites of the body, the drug encapsulation method is not always well elucidated. In this work, solid lipid nanoparticles (SLN) composed by stearic acid or cetostearyl alcohol were prepared by a hot homogenization method using poly(vinyl alcohol) or polysorbate as surfactant and loaded with hesperidin, a bioflavonoid that possesses many pharmacological properties. The obtained SLN were characterized by several physicochemical techniques to identify interactions between the constituents and to evaluate the drug incorporation into the nanoparticles. According to scanning electron microscopy and dynamic light scattering the hesperidin-loaded and unloaded SLN have spherical shapes, sizes ranging from 300 to 600 nm, zeta potentials varying from -35 to -20 mV, polydispersity indexes between 0.240 and 0.445, and entrapment efficiencies higher than 88%. X-ray diffraction showed the hesperidin amorphization due to its encapsulation in SLN, and also showed crystallization degree and polymorphic modification of the lipids after the SLN preparation. FTIR, Raman and Photoacoustic spectroscopy revealed no chemical reactions between drug and lipids, however, these results indicated that the drug was incorporated differently into nanoparticles based on the SLN composition. The analysis showed that stearic acid-based SLN prepared with polysorbate were more efficient to enclosure the hesperidin while the glycosydic part of the hesperidin was not entrapped in the cetostearyl alcohol-based SLN; instead, the hesperidin remained on the SLN surface due to lipid crystallization. The physicochemical characterization allowed identifying different types of hesperidin incorporation into the SLN, which can interact in a varied manner as targeted drug delivery systems.

Floating ability and drug release evaluation of gastroretentive microparticles system containing metronidazole obtained by spray drying

Abstract Gastroretentive floating microparticles were developed and evaluated for the controlled metronidazole delivery for treatment of gastric disease. Floating microparticles, varying in proportions of chitosan and hydroxypropyl methylcellulose or ethylcellulose, were obtained by spray drying. Floating microparticles were characterized by physicochemical and in vitro studies, according to their floating ability and drug delivery. Microparticles presented mean diameter from 1.05 to 2.20 µm. The infrared spectroscopy confirmed the drug encapsulation and showed no chemical linkage between microparticles components. X-ray diffraction showed changes in the drug`s solid state, from crystalline to amorphous, indicating partial drug encapsulation, due to the presence of some crystalline peaks of metronidazole in microparticles. All microparticles floated immediately in contact of simulated gastric fluid and both floating and drug release profiles were dependent of microparticles composition. Microparticles samples constituted by chitosan and hydroxypropyl methylcellulose revealed the best relationship between floating duration and drug release, remaining floating during the occurrence of the drug release, ideal condition for the floating gastroretentive systems.

A simple HPLC method for the determination of halcinonide in lipid nanoparticles: development, validation, encapsulation efficiency, and in vitro drug permeation

ABSTRACT Halcinonide is a high-potency topical glucocorticoid used for skin inflammation treatments that presents toxic systemic effects. A simple and quick analytical method to quantify the amount of halcinonide encapsulated into lipid nanoparticles, such as polymeric lipid-core nanoparticles and solid lipid nanoparticles, was developed and validated regarding the drug's encapsulation efficiency and in vitro permeation. The development and validation of the analytical method were carried out using the high performance liquid chromatography with the UV detection at 239 nm. The validation parameters were specificity, linearity, precision and accuracy, limits of detection and quantitation, and robustness. The method presented an isocratic flow rate of 1.0 mL.min-1, a mobile phase methanol:water (85:15 v/v), and a retention time of 4.21 min. The method was validated according to international and national regulations. The halcinonide encapsulation efficiency in nanoparticles was greater than 99% and the in vitro drug permeation study showed that less than 9% of the drug permeated through the membrane, indicating a nanoparticle reservoir effect, which can reduce the halcinonide's toxic systemic effects. These studies demonstrated the applicability of the developed and validated analytical method to quantify halcinonide in lipid nanoparticles.

A novel automated alternating current biosusceptometry method to characterization of controlled-release magnetic floating tablets of metronidazole.

CONTEXT: Alternating Current Biosusceptometry is a magnetically method used to characterize drug delivery systems. This work presents a system composed by an automated ACB sensor to acquire magnetic images of floating tablets. OBJECTIVE: The purpose of this study was to use an automated Alternating Current Biosusceptometry (ACB) to characterize magnetic floating tablets for controlled drug delivery. MATERIALS AND METHODS: Floating tablets were prepared with hydroxypropyl methylcellulose (HPMC) as hydrophilic gel material, sodium bicarbonate as gas-generating agent and ferrite as magnetic marker. ACB was used to characterize the floating lag time and the tablet hydration rate, by quantification of the magnetic images to magnetic area. Besides the buoyancy, the floating tablets were evaluated for weight uniformity, hardness, swelling and in vitro drug release. RESULTS: The optimized tablets were prepared with equal amounts of HPMC and ferrite, and began to float within 4 min, maintaining the flotation during more than 24 h. The data of all physical parameters lied within the pharmacopeial limits. Drug release at 24 h was about 40%. CONCLUSIONS: The ACB results showed that this study provided a new approach for in vitro investigation of controlled-release dosage forms. Moreover, using automated ACB will also be possible to test these parameters in humans allowing to establish an in vitro.in vivo correlation (IVIVC).

Development and in vitro evaluation of coated pellets containing chitosan to potential colonic drug delivery.

In this work pellets containing chitosan for colonic drug delivery were developed. The influence of the polysaccharide in the pellets was evaluated by swelling, drug dissolution and intestinal permeation studies. Drug-loaded pellets containing chitosan as swellable polymer were coated with an inner layer of Kollicoat(®) SR 30 D and an outer layer of the enteric polymer Kollicoat(®) MAE 30 DP in a fluidized-bed apparatus. Metronidazole released from pellets was assessed using Bio-Dis dissolution method. Swelling, drug release and intestinal permeation were dependent on the chitosan and the coating composition. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously. The film coating was found to be the main factor controlling the drug release and the chitosan controlling the drug intestinal permeation. Coated pellets containing chitosan show great potential as a system for drug delivery to the colon.