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AIM: This study investigated the effectiveness of a drug-modified tissue conditioner in an animal model of denture stomatitis. METHODS AND RESULTS: Wistar rats wore a Candida albicans-contaminated palatal device for 4 days. Next, nystatin (Nys) or chlorhexidine (Chx) were added to a tissue conditioner in their raw or ß-cyclodextrin-complexed (ßCD) forms at their minimum inhibitory concentrations. As controls, one group was not subjected to any procedure (NC), one group used sterile devices, one group had denture stomatitis but was not treated (DS), and another had the devices relined with the tissue conditioner without the addition of any drug (Soft). After 4 days of treatment, treatment effectiveness was assessed visually, histologically, and through CFU count, and myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) assays. Rats from the Soft, Nys, Nys:ßCD, and Chx groups presented a significant decrease in the microbial load compared with the untreated group. Treatment groups showed lower MPO and NAG activity compared to the non-treated group. CONCLUSIONS: The addition of antifungals to a soft tissue conditioner can be a promising approach for denture stomatitis treatment.
Assuntos
Antifúngicos , Candida albicans , Clorexidina , Nistatina , Ratos Wistar , Estomatite sob Prótese , Animais , Estomatite sob Prótese/microbiologia , Estomatite sob Prótese/tratamento farmacológico , Ratos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Nistatina/farmacologia , Nistatina/uso terapêutico , Clorexidina/farmacologia , Candida albicans/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Contagem de Colônia Microbiana , Testes de Sensibilidade Microbiana , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/microbiologia , Peroxidase/metabolismo , Acetilglucosaminidase/metabolismo , beta-CiclodextrinasRESUMO
The emergence of resistant fungal species and the toxicity of currently available antifungal drugs are relevant issues that require special consideration. Cyclodextrins inclusion complexes could optimize the antimicrobial activity of such drugs and create a controlled release system with few side effects. This study aimed to assess the in vitro toxicity and antifungal effectiveness of nystatin (Nys) and chlorhexidine (Chx) complexed or not with ß-cyclodextrin (ßCD). First, a drug toxicity screening was performed through the Artemia salina bioassay. Then, the minimum inhibitory concentrations (MICs) against Candida albicans were determined with the broth microdilution test. After MICs determination, the cytotoxicity of the drugs was evaluated through the methyl-thiazolyl-tetrazolium (MTT) and neutral red (NR) assays and through cell morphology analysis. The PROBIT analysis was used to determine the median lethal concentration (LC50), and the cell viability values were submitted to one-way analysis of variance(ANOVA)/Tukey (α = 0.05). Overall, the ßCD-complexed antifungals were less toxic against A. salina than their raw forms, suggesting that inclusion complexes can reduce the toxicity of drugs. The MICs obtained were as follows: Nys 0.5 mg/L; Nys:ßCD 4 mg/L; Chx 4 mg/L; and Chx:ßCD 8 mg/L. Chx showed significant cytotoxicity (MTT: 12.9 ± 9.6%; NR: 10.6 ± 12.5%) and promoted important morphological changes. Cells exposed to the other drugs showed viability above 70% with no cellular damage. These results suggest that antifungals complexed with ßCD might be a biocompatible option for the treatment of Candida-related infections.
Assuntos
Antifúngicos , beta-Ciclodextrinas , Antifúngicos/toxicidade , Candida , Nistatina/toxicidade , Candida albicans , Clorexidina/farmacologia , beta-Ciclodextrinas/toxicidadeRESUMO
Aim: The study aimed to review experimental models using cyclodextrins to improve antibacterial drugs' physicochemical characteristics and biological activities. Methods: The following terms and their combinations were used: cyclodextrins and antibacterial agents in title or abstract, and the total study search was conducted over a period up to October 2022. The review was carried out using PubMed, Scopus and Embase databases. A total of 1580 studies were identified, of which 27 articles were selected for discussion in this review. Results: The biological results revealed that the antibacterial effect of the inclusion complexes was extensively improved. Cyclodextrins can enhance the therapeutic effects of antibiotics already existing on the market, natural products and synthetic molecules. Conclusion: Overall, CDs as drug-delivery vehicles have been shown to improve antibiotics solubility, stability, and bioavailability, leading to enhanced antibacterial activity.
The overuse of drugs can cause bacteria to become less susceptible to them. This is known as resistance. One idea on how to tackle this resistance is by using cyclodextrins (CDs). CDs can change how drugs work, making them better at fighting bacteria. As CDs are already used in making drugs, they are a good choice for the basis of creating new drugs.
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Ciclodextrinas , Antibacterianos/farmacologia , Ciclodextrinas/farmacologia , SolubilidadeRESUMO
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.
Assuntos
Clorexidina , beta-Ciclodextrinas , Clorexidina/farmacologia , Antifúngicos/farmacologia , Candida albicans , beta-Ciclodextrinas/farmacologia , beta-Ciclodextrinas/químicaRESUMO
Pterostilbene (PTS) is a drug candidate with low water solubility and poor bioavailability. On the other hand, drug:cyclodextrins complexes frequently provide bulk powders with low drug concentrations, which is crucial for obtention solid or semi-solid pharmaceutical dosage forms. In order to determine the optimal conditions for enhancing the solubility of PTS:BCD (ß-cyclodextrin) complex, a Box-Behnken design was performed. Although the optimal conditions have been applied, low complexation efficiency (0.127) and the bulk powder remained. A PTS:BCD:HPMC (HPMC, hydroxypropyl methylcellulose) ternary system was developed to overcome this limitation, comparing two media, water and a mixture of ethanol-water. When ethanol was used as a co-solvent, the PTS:BCD:HPMC ternary system (freeze-dried) contained 116.65 ± 1.40 mg/g of PTS. This value was 3.4-fold higher than the PTS content observed when the same ternary system was obtained in aqueous media (34.8 mg/g) and 2.8-fold higher than the PTS content observed for PTS:BCD complex (freeze-dried) obtained using ethanol as a co-solvent. Dissolution tests revealed that after 120 min, in a buffer with a pH value of 1.2, only 43% of PTS dissolved. In contrast, 80% and 90% of PTS were dissolved from the PTS:BCD complex and PTS:BCD:HPMC ternary system, respectively. Moreover, the dissolution was fast in a buffer with a pH value of 6.8. PTS:BCD complex reached the maximum PTS dissolution at 75 min and PTS:BCD:HPMC at 45 min. In summary, the results of this study demonstrated, for the first time, that low-bulk powders with a high content of PTS can be obtained from PTS:BCD:HPMC ternary systems using ethanol as a co-solvent. This new finding offers a valuable alternative for producing solid or semi-solid formulations containing highly soluble PTS.
Assuntos
Química Farmacêutica , Água , Solubilidade , Pós , Química Farmacêutica/métodos , Derivados da Hipromelose , Água/química , SolventesRESUMO
BACKGROUND: ß-lapachone (ß-lap) is a naphthoquinone widely found in species of vegetables. However, its poor aqueous solubility limits its systemic administration and clinical applications in vivo. To overcome this limitation, several studies have been carried out in order to investigate techniques that can enhance the solubility and dissolution rate of ß-lap, such as the use of inclusion complexes with cyclodextrin. PURPOSE: To evaluate the in vivo effect of ß-lap complexed in methyl-ß-cyclodextrin (MßCD) on the evolutionary stages of Schistosoma mansoni in a murine model. METHODS: The development and characterization of the physicochemical properties of the inclusion complex of ß-lap in ß-lap:MßCD was prepared by solubility and dissolution tests, FTIR, DSC, X-RD and SEM. The mice were infected and subsequently treated with ß-lap:MßCD orally with 50 mg/kg/day and 100 mg/kg/day for 5 consecutive days, starting therapy on the 1st (skin schistosomula), 14th (pulmonary schistosomula), 28th (young worms) and 45th (adult worms) days after infection. Control groups were also formed; one infected untreated, treated with MßCD, and the other treated with PZQ. RESULTS: The loss of the crystalline form of ß-lap in the ß-lap:MßCD complex obtained by spray drying was proven through physical-chemical characterization analyses. ß-lap:MßCD caused reduction in the number of worms of the 33.56%, 35.7%, 35.45% and 36.45%, when the dose was at 50 mg/kg, and 65.00%, 60.34%, 52.72% and 65.01%, in the dose 100 mg/kg; when treatment was started in the 1st, 14th, 28th and 45th days after infection, respectively. It was also possible to observe a significant reduction in the number of immature eggs and an increase in the number of ripe and dead eggs and, consequently, a reduction in the damage caused by the egg antigens to the host tissue, where we attributed the reduction in the average diameter of the granulomas to the ß-lap. CONCLUSION: The dissolved content of ß-lap:MßCD by spray drying reached almost 100%, serving for future formulations and delineation of the mechanisms of action of ß-lap against S. mansoni.
Assuntos
Naftoquinonas , Schistosoma mansoni , Animais , Camundongos , Secagem por Atomização , Modelos Animais de Doenças , Naftoquinonas/farmacologiaRESUMO
In the early 2000s, a method for cross-linking cyclodextrins (CDs) with citric acid (CTR) was developed. This method was nontoxic, environmentally friendly, and inexpensive compared to the others previously proposed in the literature. Since then, the CD/CTR biopolymers have been widely used as a coating on implants and other materials for biomedical applications. The present review aims to cover the chemical properties of CDs, the synthesis routes of CD/CTR, and their applications as drug-delivery systems when coated on different substrates. Likewise, the molecules released and other pharmaceutical aspects involved are addressed. Moreover, the different methods of pretreatment applied on the substrates before the in situ polymerization of CD/CTR are also reviewed as a key element in the final functionality. This process is not trivial because it depends on the surface chemistry, geometry, and physical properties of the material to be coated. The biocompatibility of the polymer was also highlighted. Finally, the mechanisms of release generated in the CD/CTR coatings were analyzed, including the mathematical model of Korsmeyer-Peppas, which has been dominantly used to explain the release kinetics of drug-delivery systems based on these biopolymers. The flexibility of CD/CTR to host a wide variety of drugs, of the in situ polymerization to integrate with diverse implantable materials, and the controllable release kinetics provide a set of advantages, thereby ensuring a wide range of future uses.
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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.
Assuntos
Antifúngicos , Estomatite sob Prótese , Antifúngicos/farmacologia , Nistatina/farmacologia , Candida , Estomatite sob Prótese/tratamento farmacológico , Estomatite sob Prótese/microbiologia , Testes de Sensibilidade Microbiana , Candida albicans , Candida parapsilosisRESUMO
Hydroxycinnamic acids (HCAs) are a subclass of phenolic acids presenting caffeic acid (CA), chlorogenic acid (CGA), coumaric acid (COA) isomers, ferulic acid (FA), and rosmarinic acid (RA) as the major representants, being broadly distributed into vegetal species and showing a range of biological potentials. Due to the low oral bioavailability of the HCAs, the development of delivery systems to promote better administration by the oral route is demanding. Among the systems, cyclodextrin (CD)-based delivery systems emerge as an important technology to solve this issue. Regarding these aspects, in this review, CD-based delivery systems containing HCAs are displayed, described, and discussed concerning the degree of interaction and their effects on crucial parameters that affect the oral bioavailability of HCAs.
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(1) Background: estragole is a monoterpene found in the essential oils of several aromatic plants, which can be used for several pharmacological activities. The aim of this study was to evaluate the antinociceptive effect of estragole (Es) and its ß-cyclodextrins inclusion complex (Es/ß-CD). (2) Methods: the effects of Es and Es/ß-CD on the central nervous system (CNS) were evaluated through open field and rota-rod assays, and the antinociceptive effect in formalin models, abdominal writhing induced by acetic acid, hot plate, tail flick test and plantar mechanical hyperalgesia. (3) Results: Es and Es/ß-CD showed no alterations on the CNS evaluated parameters and the results suggested there was an antinociceptive action in the formalin, abdominal writhing, hot plate, tail flick tests and plantar mechanical hyperalgesia, proposing the involvement of the nitric oxide, glutamatergic signaling pathways, cyclic guanosine monophosphate and vanilloid pathways. (4) Conclusion: the results suggest that Es and Es/ß-CD have a promising antinociceptive potential as a possible alternative for the pharmacological treatment of pain, also showing that the encapsulation of Es in ß-cyclodextrins probably improves its pharmacological properties, since the complexation process involves much lower amounts of the compound, contributing to better bioavailability and a lower probability of adverse effect development.