Analysis of Key Factors for Evaluating Mucosal Adhesion Using Swine Buccal Tissue.

The assessment of the mucoadhesive properties peak mucoadhesive force (Fmax) and work of mucoadhesion (Wmuc) with texture analyzers is a common in vitro method for analyzing formulation capabilities. Challenges arise in selecting and standardizing experimental conditions due to various variables influencing mucoadhesion. This complexity hampers direct product performance comparisons. In our study, we explored factors (contact force and time, probe speed and mucin in artificial saliva) impacting a model formulation's mucoadhesive capacity. Using Omcilon-A®Orabase on porcine buccal mucosa, we systematically varied experimental conditions, employing a statistical approach (Central Composite Design - CCD). Three variables (contact force, contact time, probe speed) and their interactions were assessed for their impact on Fmax and Wmuc. Results showed that contact time and force positively affected Fmax, while only contact time influenced Wmuc. In the mucin artificial saliva test, a force of 0.5 N, time of 600 s, and speed of 1 mm/s yielded optimal Fmax (0.587 N) and Wmuc (0.468 N.s). These conditions serve as a reference for comparing mucoadhesive properties of formulations for topical oral use.

New Technological Approaches for Dental Caries Treatment: From Liquid Crystalline Systems to Nanocarriers.

Dental caries is the most common oral disease, with high prevalence rates in adolescents and low-income and lower-middle-income countries. This disease originates from acid production by bacteria, leading to demineralization of the dental enamel and the formation of cavities. The treatment of caries remains a global challenge and the development of effective drug delivery systems is a potential strategy. In this context, different drug delivery systems have been investigated to remove oral biofilms and remineralize dental enamel. For a successful application of these systems, it is necessary that they remain adhered to the surfaces of the teeth to allow enough time for the removal of biofilms and enamel remineralization, thus, the use of mucoadhesive systems is highly encouraged. Among the systems used for this purpose, liquid crystalline systems, polymer-based nanoparticles, lipid-based nanoparticles, and inorganic nanoparticles have demonstrated great potential for preventing and treating dental caries through their own antimicrobial and remineralization properties or through delivering drugs. Therefore, the present review addresses the main drug delivery systems investigated in the treatment and prevention of dental caries.

Liquid crystal precursor system as a vehicle for curcumin-mediated photodynamic inactivation of oral biofilms.

Curcumin has great potential as a photosensitizer, but it has low solubility in aqueous solutions. This study reports the antimicrobial efficacy of photodynamic inactivation (PDI) mediated by a curcumin-loaded liquid crystal precursor (LCP) on in situ dental biofilms. Thirty volunteers used intraoral devices containing enamel samples for 48 hours for biofilm formation. The samples were then removed from the device and treated either with LCP with 160 µM of curcumin plus illumination at 18 J/cm2 (C + L+ group) or with LCP without curcumin in the dark (C - L - group). Following this, the biofilm from the samples was plated for quantifying the viable colonies at 37°C for 48 hours. Specific and nonspecific media were used for the presumptive isolation of Streptococcus mutans, Lactobacillus species/aciduric microorganisms, Candida species, and total microbiota. The C + L+ group showed a highly significant (P < .001) reduction in the log10 (colony forming units/mL) values as compared to the C - L - group for all culture media. Hierarchical linear regression indicated that there may be predictors at individual volunteer level explaining the difference in the PDI efficacy among different individuals (P = .001). The LCP system retained curcumin and released it slowly and continuously, thus protecting the drug from photodegradation. LCP with curcumin is considered effective for the photoinactivation of dental biofilms, but the PDI efficacy may differ based on the host's individual characteristics.

Potential of curcumin-loaded cubosomes for topical treatment of cervical cancer.

Cervical cancer is one of the most common cancers affecting women worldwide. There are an estimated 570.000 new cases of cervical cancer each year and conventional treatments can cause severe side effects. In this work, we developed a platform for vaginal administration of lipophilic drugs for cervical cancer treatment. We formulated mucoadhesive cubosomes for the delivery of curcumin, a lipophilic drug for cervical cancer treatment, to increase its bioavailability and local absorption. This study tests the use of cubosomes for vaginal drug administration and assesses their potential efficiency using the CAM (chick embryo chorioallantoic membrane) model. SAXS (small-angle X-ray scattering), cryo-TEM (cryo-transmission electron microscopy), and dynamic light scattering (DLS) were employed to characterise the system. With ex vivo permeation and retention studies, we find that the curcumin released from our system is retained in the vaginal mucosa. In vitro cytotoxicity assay and cellular uptake showed an increased cytotoxic effect of curcumin against HeLa cell line when incorporated into the cubosomes. The curcumin-loaded cubosomes also demonstrated an antiangiogenic effect evaluated in vivo by the CAM model.

Mucoadhesive, Thermoreversible Hydrogel, Containing Tetracaine-Loaded Nanostructured Lipid Carriers for Topical, Intranasal Needle-Free Anesthesia.

Recent advances have been reported for needle-free local anesthesia in maxillary teeth by administering a nasal spray of tetracaine (TTC) and oxymetazoline, without causing pain, fear, and stress. This work aimed to assess whether a TTC-loaded hybrid system could reduce cytotoxicity, promote sustained permeation, and increase the anesthetic efficacy of TTC for safe, effective, painless, and prolonged analgesia of the maxillary teeth in dental procedures. The hybrid system based on TTC (4%) encapsulated in nanostructured lipid carriers (NLC) and incorporated into a thermoreversible hydrogel of poloxamer 407 (TTCNLC-HG4%) displayed desirable rheological, mechanical, and mucoadhesive properties for topical application in the nasal cavity. Compared to control formulations, the use of TTCNLC-HG4% slowed in vitro permeation of the anesthetic across the nasal mucosa, maintained cytotoxicity against neuroblastoma cells, and provided a three-fold increase in analgesia duration, as observed using the tail-flick test in mice. The results obtained here open up perspectives for future clinical evaluation of the thermoreversible hybrid hydrogel, which contains TTC-loaded NLC, with the aim of creating an effective, topical, intranasal, needle-free anesthesia for use in dentistry.

Bioadhesive Curcumin-Mediated Photodynamic Inactivation and Its Potential to Cause Undesirable Effects on Dental and Restorative Surfaces.

Curcumin-mediated Photodynamic Inactivation (PDI) has shown great potential to disinfect specific sites on tooth enamel but may involve contact with restorative materials. Thus, before use in dentistry, it is necessary to investigate whether the PDI protocol causes undesirable changes in the surfaces of aesthetic restorative materials and dental enamel. This study investigated the effect of PDI mediated by curcumin (CUR) in a liquid crystal precursor system on color stability (ΔE), surface roughness (Ra), and microhardness (kgf) of three different composite resins and bovine dental enamel specimens. The microhardness and roughness readings were performed 60 days after the treatments while the color readings were performed immediately, 24, 48, and 72 h, 7, 14, 21, 30, and 60 days after the treatments. Results showed that CUR mediated-PDI does not seem to have the potential to promote any esthetic or mechanical changes to the surface of tooth enamel and can be applied safely in clinical practice. However, the results on color, roughness, and hardness obtained for composite resins show that some negative effects can be produced, depending on the type of restorative material; more experiments must be performed with different formulations and, perhaps, with lower concentrations of CUR.

Photodynamic potential of curcumin in bioadhesive formulations: Optical characteristics and antimicrobial effect against biofilms.

BACKGROUND: Although Curcumin (CUR) has great potential as a photosensitizer, the low solubility in water impairs its clinical performance in photodynamic inactivation (PDI). This study sought to establish an effective antimicrobial protocol for PDI using CUR in three different bioadhesive formulations. METHODS: A CUR-loaded chitosan hydrogel with a poloxamer (CUR-CHIH), a CUR-loaded liquid crystal precursor system (CUR-LCP), a CUR-loaded microemulsion (CUR-ME), and CUR in dimethylsulfoxide (DMSO) solution (CUR-S; control formulation) were tested against in vitro and in situ oral biofilms. The optical properties of each formulation were evaluated. RESULTS: All of the formulations exhibited lower absorbance than CUR-S; however, the CUR-LCP curve bore the highest resemblance. The CUR present in all formulations was completely degraded after 15 min of illumination. In vitro experiments showed that CUR-S was the only formulation able to significantly reduce biofilm viability of Candida albicans and Lactobacillus casei when compared to the negative control (no PDI); the amount of reduction obtained was 1.8 and 3.7 log (CFU/mL) for C. albicans and L. casei, respectively. There was a significant reduction on the viability of Streptococcus mutans biofilms when CUR-S and CUR-LCP were applied (approximately 3.5 and 1.6 log [CFU/mL], respectively). In situ testing showed antimicrobial efficacy against S. mutans and general microorganisms. CONCLUSIONS: Although the evaluated protocols has not been effective to all of the evaluated microorganisms, PDI showed potential against dental biofilms and evidence that the phototoxic effects of CUR have a high relation with the type of formulation in which it is loaded.

Innovative Mucoadhesive Precursor of Liquid Crystalline System Loading Anti-Gellatinolytic Peptide for Topical Treatment of Oral Cancer.

Current researches report an actual benefit of a treatment for oral cancer via inhibition of proteolytic matrix metallopro-teinases (MPP) with a peptide drug, called CTT1. However, peptides present poor oral bioavailability. Topical administration on oral mucosa avoids its passage through the gastrointestinal tract and the first-pass liver metabolism, but the barrier function of the oral mucosa can impair the permeation and retention of CTT1. The objective of this study is to incorporate CTT1 into a mucoadhesive precursor of liquid crystalline system (PLCS) as an interesting strategy for the topical treatment of oral cancer. PLCS consisting of oleic acid, ethoxylated 20 and propoxylated cetyl alcohol 5, polyethyleneimine (P)-associated chitosan (C) dispersion and CTT1 (FPC-CTT1) was developed and characterized by polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). In vitro permeation and retention across esophageal mucosa, In vitro cytotoxicity towards tongue squamous cell carcinoma cells, and in vivo evaluation of vascular changes using the chick embryo chorioallantoic membrane (CAM) model were performed. PLM and SAXS showed that FPC-CTT1acted as PLCS, because it formed a lamellar liquid crystalline system after the addition of artificial saliva. FPC-CTT1increased approximately 2-fold the flux of permeation and 3-fold the retention of CTT1 on the porcine esophageal mucosa. CTT1 does not affect cell viability. CAM tests showed that FPC preserved the blood vessels and it can be a safe formulation. These findings encourage the use of the FPC-CTT1 for topical treatment of oral cancer.

In vivo study of hypericin-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system in a mice model of vulvovaginal candidiasis.

The present study reports the performance of the pigment hypericin (HYP)-loaded poloxamer-based mucoadhesive in situ gelling liquid crystalline precursor system (LCPS) for the treatment of vulvovaginal candidiasis (VVC) in mice. LCPS composed of 40% of ethoxylated and propoxylated cetyl alcohol, 30% of oleic acid and cholesterol (7:1), 30% of a dispersion of 16% poloxamer 407 and 0.05% of HYP (HYP-LCPS) was prepared and characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS) and ex vivo permeation and retention studies across vaginal porcine mucosa were performed. In addition, the antifungal properties of the HYP-LCPS were evaluated in a murine in vivo model; for this, infected C57BL female mice groups were treated with both HYP in solution and HYP-LCPS, and after 6 days colony forming unit (CFU)/ml count was performed. PLM and SAXS confirmed that HYP-LCPS is a microemulsion situated in boundary transition region confirming its action as an LCPS. When in contact with simulated vaginal fluid, HYP-LCPS became rigid and exhibited maltase crosses and bragg peaks characteristics of lamellar phase. Ex vivo permeation and retention studies showed that HYP-LCPS provides a localized treatment on the superficial layers of porcine vaginal mucosa. HYP-LCPS induced a significant reduction in the number of CFU/ml in the mice; thus this formulation indicated it is as effective as a commercial dosage form. It was concluded that LCPS maintains the biological activity of HYP and provides an adequate drug delivery system for this lipophilic molecule at the vaginal mucosa, being a promising option in cases of VVC.

Terpinen-4-ol and nystatin co-loaded precursor of liquid crystalline system for topical treatment of oral candidiasis.

This study was performed to develop a liquid crystalline system (LCS) incorporated with terpinen-4-ol and nystatin to evaluate its antifungal, antibiofilm, and synergistic/modulatory activity against Candida albicans. The LCS was composed of a dispersion containing 40% propoxylated and ethoxylated cetyl alcohol, 40% oleic acid, and 0.5% chitosan dispersion. According to analysis by polarized light microscopy, rheology, and mucoadhesion studies, the incorporation of 100% artificial saliva increased the pseudoplasticity, consistency index, viscosity, and mucoadhesion of the formulation. The minimum inhibitory concentration, minimum fungicidal concentration, and rate of biofilm development were used to evaluate antifungal activity; the LCS containing terpinen-4-ol and nystatin effectively inhibited C. albicans growth at a lower concentration, displaying a synergistic action. Therefore, LCS incorporated with terpinen-4-ol and nystatin is a promising alternative for preventing and treating infections and shows potential for the development of therapeutic strategies against candidiasis.

Chick embryo chorioallantoic membrane as a suitable in vivo model to evaluate drug delivery systems for cancer treatment: A review.

Cancer represents a significant public health problem. More than 18.1 million people are annually diagnosed with cancer and 9.6 million die mainly due to metastatic disease. Chemotherapy has been one of the main cancer treatment modalities; however, most of the chemotherapeutic agents are non-specific, exhibiting several toxic side effects, which compromises the patient's quality of life. Therefore, it is necessary to search for new therapeutic alternatives, using for example, drug delivery systems (DDS) to target cancer cells, increasing the selectivity of chemotherapeutic drugs. This approach is promising; however, it is crucial to evaluate the biological performance of the systems. Although mammalian models continue to be explored for clinical applications, they are time-consuming and very restrictive from the ethical and legal perspectives. Hence, the chick embryo chorioallantoic membrane (CAM) has been shown to be a suitable in vivo model since it allows a more appropriate model for the study of drugs and/or DDS performance than in vitro tests. Thereby, this article revises the recent advances of DDS for cancer therapy, evaluating the feasibility of the CAM model.

Chitosan-Based Drug Delivery Systems for Optimization of Photodynamic Therapy: a Review.

Drug delivery systems (DDS) can be designed to enrich the pharmacological and therapeutic properties of several drugs. Many of the initial obstacles that impeded the clinical applications of conventional DDS have been overcome with nanotechnology-based DDS, especially those formed by chitosan (CS). CS is a linear polysaccharide obtained by the deacetylation of chitin, which has potential properties such as biocompatibility, hydrophilicity, biodegradability, non-toxicity, high bioavailability, simplicity of modification, aqueous solubility, and excellent chemical resistance. Furthermore, CS can prepare several DDS as films, gels, nanoparticles, and microparticles to improve delivery of drugs, such as photosensitizers (PS). Thus, CS-based DDS are broadly investigated for photodynamic therapy (PDT) of cancer and fungal and bacterial diseases. In PDT, a PS is activated by light of a specific wavelength, which provokes selective damage to the target tissue and its surrounding vasculature, but most PS have low water solubility and cutaneous photosensitivity impairing the clinical use of PDT. Based on this, the application of nanotechnology using chitosan-based DDS in PDT may offer great possibilities in the treatment of diseases. Therefore, this review presents numerous applications of chitosan-based DDS in order to improve the PDT for cancer and fungal and bacterial diseases.

Mucoadhesive In Situ Gelling Liquid Crystalline Precursor System to Improve the Vaginal Administration of Drugs.

The vaginal mucosa is a very promising route for drug administration due to its high permeability and the possibility to bypass first pass metabolism; however, current vaginal dosage forms present low retention times due to their dilution in vaginal fluids, which hampers the efficacy of many pharmacological treatments. In order to overcome these problems, this study proposes to develop a mucoadhesive in situ gelling liquid crystalline precursor system composed of 30% of oleic acid and cholesterol (7:1), 40% of ethoxylated and propoxylated cetyl alcohol, and 30% of a dispersion of 16% Poloxamer 407. The effect of the dilution with simulated vaginal fluid (SVF) on this system was evaluated by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological studies, texture profile analysis (TPA), mucoadhesion study, in vitro drug release test using hypericin (HYP) as drug model, and cytotoxicity assay. PLM and SAXS confirmed the formation of an isotropic system. After the addition of three different concentrations of SVF (30, 50, and 100%), the resultant formulations presented anisotropy and characteristics of viscous lamellar phases. Rheology shows that formulations with SVF behaved as a non-Newtonian fluid with suitable shear thinning for vaginal application. TPA and mucoadhesion assays indicated the formation of long-range ordered systems as the amount of SVF increases which may assist in the fixation of the formulation on the vaginal mucosa. The formulations were able to control about 75% of the released HYP demonstrating a sustained release profile. Finally, all formulations acted as safe vaginal drug delivery systems.

Curcumin-Loaded Liquid Crystalline Systems for Controlled Drug Release and Improved Treatment of Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC) is the most common infection caused by Candida albicans and greatly reduces the quality of life of women affected by it. Due to the ineffectiveness of conventional treatments, there is growing interest in research involving compounds of natural origin. One such compound is curcumin (CUR), which has been proven to be effective against this microorganism. However, some of CUR's physicochemical properties, especially its low aqueous solubility, make the therapeutic application of this compound difficult. Thus, the incorporation of CUR in mucoadhesive liquid crystalline systems (MLCSs) for vaginal administration may be an efficient strategy for the treatment of VVC. MLCSs are capable of potentiating the compound's action, releasing it in a controlled manner, and can enable longer exposure at the site of infection. In this study, MLCSs consisting of oleic acid and ergosterol 5:1 (w/w) as the oily phase, PPG-5-CETETH-20 as the surfactant, and a polymer dispersion of 1% chitosan as the aqueous phase, were developed for the application of CUR (MLCS-CUR) in VVC treatment. The formulations were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), oscillatory rheometry, continuous shear rheometry, texture profile analysis, and in vitro mucoadhesion. In addition, the antimicrobial activity was evaluated in vitro, and the effects on local fungal burden and cytokine profiles were investigated in a murine model of VVC. PLM and SAXS showed that the developed formulations presented a characteristic of a microemulsion. However, after the addition of artificial vaginal mucus (AVM), PLM showed that the formulations had structures similar to the "Maltese cross" characteristic of lamellar MLCS. Mucoadhesive test results showed an increase in the mucoadhesive strength of these formulations. Rheology analyses suggested long-lasting action of the formulation at the infected site. The in vitro antimicrobial activity assays suggested that CUR possesses antifungal activity against Candida albicans, determined after its incorporation into the MLCS. Further, MLCS-CUR was also more effective in vivo in the control of vaginal infection than treatment with fluconazole. Immunological assays showed that the ratio of pro-inflammatory (IL-1ß) to anti-inflammatory (TGF-ß) cytokines has decreased and that there is a reduction in the number of polymorphonuclear neutrophils recruited to the vaginal lumen, showing that treatment with MLCS-CUR was effective in modulating the inflammatory reaction associated with the infection. The results suggest that MLCSs could potentially be used in the treatment of VVC with CUR.

Antimicrobial peptide-loaded liquid crystalline precursor bioadhesive system for the prevention of dental caries.

BACKGROUND: Anticaries agents must interfere with the adhesion of Streptococcus mutans and its proliferation in dental biofilm, without causing host toxicity and bacterial resistance. Natural substances, including cationic antimicrobial peptides (CAMPs) and their fragments, such as ß-defensin-3 peptide fragment (D1-23), have been widely studied. However, the chemical and physical stability of CAMPs may be compromised by external factors, such as temperature and pH, reducing the period of antimicrobial activity. METHODS: To overcome the aforementioned disadvantage, this study developed and character-ized a drug delivery system and evaluated the cytotoxicity and effect against S. mutans biofilm of a D1-23-loaded bioadhesive liquid crystalline system (LCS). LCS was composed of oleic acid, polyoxypropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, Carbopol® 974P and Carbopol® 971P. LCS was analyzed by polarized light microscopy (PLM), rheology (viscoelasticity and flow properties) and in vitro bioadhesion. The viability of epithelial cells was evaluated. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against S. mutans were determined for D1-23 for further evaluation of the effect against S. mutans biofilm after 4 and 24 h of exposure to treatments. RESULTS: PLM, rheology, and in vitro bioadhesion tests showed that both viscosity and bioadhesion of LCS increased after it was diluted with artificial saliva. D1-23-loaded LCS system presented better activity against S. mutans biofilm after 24 h when compared to 4 h of treatment, showing a cumulative effect. Neither LCS nor D1-23-loaded LCS presented toxicity on human epithelial cells. CONCLUSION: D1-23-loaded LCS is a promising drug delivery system for the prevention of dental caries.

Assessment of Chitosan-Based Hydrogel and Photodynamic Inactivation against Propionibacterium acnes.

Chitosan (CH) is a biopolymer that exhibits a number of interesting properties such as anti-inflammatory and antibacterial activity and is also a promising platform for the incorporation of photosensitizing agents. This study aimed to evaluate the efficacy of antimicrobial activity of chitosan hydrogel formulation alone and in combination with the methylene blue (MB) associated with antimicrobial photodynamic therapy (aPDT) against planktonic and biofilm phase of Propionibacterium acnes. Suspensions were sensitized with 12.5, 25.0, 37.5, 50.0 µg/mL of MB for 10 min and biofilms to 75, 100 and 150 µg/mL for 30 min then exposed to red light (660 nm) at 90 J/cm² and 150 J/cm² respectively. After treatments, survival fractions were calculated by counting the number of colony-forming units. The lethal effect of aPDT associated with CH hydrogel in planktonic phase was achieved with 12.5 µg/mL MB and 1.9 log10 biofilm reduction using 75 µg/mL MB. Rheological studies showed that formulations exhibited pseudoplastic non-Newtonian behavior without thixotropy. Bioadhesion test evidenced that the formulations are highly adhesive to skin and the incorporation of MB did not influence the bioadhesive force of the formulations.

Metronidazole-Loaded Polyethyleneimine and Chitosan-Based Liquid Crystalline System for Treatment of Staphylococcal Skin Infections.

Staphylococcus aureus is a common gram-positive bacterium of the human skin microbiota. It is also a dangerous pathogen that can cause serious and even lethal skin infections. The topical administration of metronidazole via nanotechnology-based drug delivery systems, such as liquid crystalline systems, can modulate both the drug permeation and activity, decreasing its side effects and increasing the drug potent activity against the gram-positive bacteria. This study aimed at: (1) structurally developing and characterizing a liquid crystalline systems composed of chitosan and polyethyleneimine dispersion as the aqueous phase, oleic acid as the oily phase, and ethoxylated and propoxylated cetyl alcohol as the surfactant (FPC) for metronidazole incorporation (0.5% w/w); (2) evaluating the in vitro release and skin permeation and retention properties of the metronidazole-loaded liquid crystalline systems (FPC-M); (3) investigating the in vitro antibacterial activity of FPC-M against Staphylococcus aureus. Polarised light microscopy indicated that both FPC and FPC-M are hexagonal systems. Rheological, texture, and bioadhesion assays showed that both are elastic and bioadhesive systems. According to the results of the in vitro release, permeation, and retention assays, FPC can modulate metronidazole release and allow metronidazole to stay for a longer time on the skin. The determination of FPC-M activity against Staphylococcus aureus showed that it could target the bacterial cell. In conclusion, the liquid crystalline systems developed in this study can improve the clinical performance of metronidazole in the treatment of staphylococcal skin infections.

Development and characterization of p1025-loaded bioadhesive liquid-crystalline system for the prevention of Streptococcus mutans biofilms.

Formation of a dental biofilm by Streptococcus mutans can cause dental caries, and remains a costly health problem worldwide. Recently, there has been a growing interest in the use of peptidic drugs, such as peptide p1025, analogous to the fragments 1025-1044 of S. mutans cellular adhesin, responsible for the adhesion and formation of dental biofilm. However, peptides have physicochemical characteristics that may affect their biological action, limiting their clinical performance. Therefore, drug-delivery systems, such as a bioadhesive liquid-crystalline system (LCS), may be attractive strategies for peptide delivery. Potentiation of the action of LCS can be achieved with the use of bioadhesive polymers to prolong their residence on the teeth. In line with this, three formulations - polyoxypropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, oleic acid, and Carbopol C974P in different combinations (F1C, F2C, and F3C) were developed to observe the influence of water in the LCS, with the aim of achieving in situ gelling in the oral environment. These formulations were assessed by polarized light microscopy, small-angle X-ray scattering, rheological analysis, and in vitro bioadhesion analysis. Then, p1025 and a control (chlorhexidine) were incorporated into the aqueous phase of the formulation (F + p1025 and F + chlorhexidine), to determine their antibiofilm effect and toxicity on epithelial cells. Polarized light microscopy and small-angle X-ray scattering showed that F1C and F2C were LCS, whereas F3C was a microemulsion. F1C and F2C showed pseudoplastic behavior and F3C Newtonian behavior. F1C showed the highest elastic and bioadhesive characteristics compared to other formulations. Antibiofilm effects were observed for F + p1025 when applied in the surface-bound salivary phase. The p1025-loaded nanostructured LCS presented limited cytotoxicity and effectively reduced S. mutans biofilm formation, and could be a promising p1025-delivery strategy to prevent the formation of S. mutans dental biofilm.

Polyethyleneimine and Chitosan Polymer-Based Mucoadhesive Liquid Crystalline Systems Intended for Buccal Drug Delivery.

The buccal mucosa is accessible, shows rapid repair, has an excellent blood supply, and shows the absence of the first-pass effect, which makes it a very attractive drug delivery route. However, this route has limitations, mainly due to the continuous secretion of saliva (0.5 to 2 L/day), which may lead to dilution, possible ingestion, and unintentional removal of the active drug. Nanotechnology-based drug delivery systems, such as liquid crystalline systems (LCSs), can increase drug permeation through the mucosa and thereby improve drug delivery. This study aimed at developing and characterizing the mechanical, rheological, and mucoadhesive properties of four liquid crystalline precursor systems (LCPSs) composed of four different aqueous phases (i) water (FW), (ii) chitosan (FC), (iii) polyethyleneimine (FP), or (iv) both polymers (FPC); oleic acid was used as the oil phase, and ethoxylated and propoxylated cetyl alcohol was used as the surfactant. Polarized light microscopy and small-angle X-ray scattering indicated that all LCPSs formed liquid crystalline states after incorporation of saliva. Rheological, texture, and mucoadhesive assays showed that FPC had the most suitable characteristics for buccal application. In vitro release study showed that FPC could act as a controlled drug delivery system. Finally, based on in vitro cytotoxicity data, FPC is a safe buccal drug delivery system for the treatment of several buccal diseases.

Trans-resveratrol-loaded nonionic lamellar liquid-crystalline systems: structural, rheological, mechanical, textural, and bioadhesive characterization and evaluation of in vivo anti-inflammatory activity.

Resveratrol (Res) is a common phytoalexin present in a few edible materials, such as grape skin, peanuts, and red wine. Evidence has shown the beneficial effects of Res on human health, which may be attributed to its anti-inflammatory activity. However, the poor aqueous solubility of Res limits its therapeutic effectiveness. Therefore, the use of nanostructured delivery systems for Res, such as liquid-crystalline systems, could be beneficial. In this study, we aimed to develop, characterize, and determine the in vivo effectiveness of Res-loaded liquid-crystalline systems. Systems containing copaiba balsam oil, polyethylene glycol-40 hydrogenated castor oil, and water were designed. Results of polarized light microscopy, small-angle X-ray scattering, texture-profile analysis, and flow-rheology analysis showed that the Res-loaded liquid-crystalline system had a lamellar structure, textural and mechanical (hardness, compressibility, and adhesiveness) properties, and behaved as a non-Newtonian fluid, showing pseudoplastic behavior upon skin application. Furthermore, all liquid-crystalline systems presented bioadhesive properties that may have assisted in maintaining the anti-inflammatory activity of Res, since the topical application of the Res-loaded lamellar mesophase liquid crystals resulted in edema inhibition in a carrageenan-induced paw-inflammation mouse model. Therefore, Res-loaded lamellar mesophases represent a promising new therapeutic approach for inhibition of skin inflammation.