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.

Candesartan exhibits low intrinsic permeation capacity and affects buccal tissue viability and integrity: An ex vivo study in porcine buccal mucosa.

Candesartan is a nonpeptide angiotensin II receptor blocker that selectively binds to angiotensin II receptor subtype 1. It is administered orally in its ester form (candesartan cilexetil). However, its poor aqueous solubility results in its low bioavailability; therefore, other routes of administration must be explored. The buccal mucosa has been extensively studied as an alternative route for drug delivery as it improves the bioavailability of drugs administered via the peroral route. Porcine buccal mucosa has been widely used as an ex vivo model to study the permeability of various diffusants; however, studies on candesartan are limited. This study aimed to evaluate the ex vivo permeation profile of candesartan and its effects on the viability and integrity of porcine buccal mucosa. Initially, we evaluated the viability, integrity, and barrier function of the buccal tissue before performing permeability tests using freshly excised tissues or tissues after 12 h of resection. Here, three indicators were used: caffeine, ß-estradiol, and FD-20 penetration; mucosal metabolic activity, as determined using MTT reduction assay; and haematoxylin and eosin staining. Our results indicated that the porcine buccal mucosa preserved its viability, integrity, and barrier function before the permeation assay, allowing the passage of molecules with a molecular mass of less than 20 kDa, such as caffeine, but not ß-estradiol and FD-20. Furthermore, we analyzed the intrinsic capacity of candesartan to diffuse through the fresh porcine buccal mucosa under two pH conditions. The concentration of candesartan in the receptor chamber of Franz diffusion cell was quantified using ultra-high liquid chromatography. In the permeation assay, candesartan exhibited a low intrinsic permeation capacity that impacted the buccal tissue viability and integrity, suggesting that using the buccal mucosa as an alternative route of administration requires developing a pharmaceutical formulation that reduces the adverse effects on mucosa and increasing the buccal permeability of candesartan.

Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone

Abstract This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.

Influence of additives on swelling and mucoadhesion properties of glyceryl monooleate liquid crystals

Abstract Liquid crystalline systems of glyceryl monooleate/water are used as drug delivery systems due to their complex structure that controls drug diffusion. Mucoadhesive properties of glyceryl monooleate suggest it can be used for buccal delivery. Using additives is a strategy to modify physical and chemical properties of liquid crystalline systems and optimize their performance as a drug delivery system. However, the presence of additives can significantly alter properties such as phase behavior, swelling and mucoadhesion. Our aim is to investigate the influence of additives on swelling and mucoadhesion of glyceryl monooleate-based liquid crystals, intending them to be used as buccal drug delivery systems. The systems were characterized regarding their mesophases, swelling rate, and mucoadhesion. All the systems studied were able to absorb water and presented mucoadhesion, which is interesting for the development of buccal drug delivery systems. Additives induced phase transitions and affected the swelling performance, while mucoadhesive properties were poorly affected. Propylene glycol increased water uptake, while oleic acid induced the phase transition to the hexagonal phase and reduced the swelling rate. The association of oleic acid (5%) and propylene glycol (10%) resulted in a cubic phase system with strong mucoadhesive properties that can be a potential drug carrier for buccal delivery.

Technological development of mucoadhesive film containing poloxamer 407, polyvinyl alcohol and polyvinylpyrrolidone for buccal metronidazole delivery.

Aim: This work aimed to develop a mucoadhesive film composed of a triblock copolymer (poloxamer 407), polyvinyl alcohol and polyvinylpyrrolidone for buccal modified delivery of metronidazole. Materials & methods: Three film formulations containing different polymer amounts were prepared by solvent casting. They were characterized as physicochemical, mechanical and mucoadhesive properties, and in vitro metronidazole release profiles. Results: Films displayed physicochemical, mechanical and mucoadhesive characteristics dependent of polymeric composition and drug presence. They could rapidly swell and promote the fast drug release (80% in 20 min) that was governed by Fickian diffusion. The films showed total disintegration in less than 90 s and total drug release in 30 min. Conclusion: Therefore, the formulations represent a promising alternative for modifying of buccal metronidazole delivery for pharmaceutical applications.

Mucoadhesive films based on gellan gum/pectin blends as potential platform for buccal drug delivery.

Films of gellan gum:pectin blends were prepared by solvent casting method. Gellan gum:pectin mass ratios were varied (4:1; 1:1; 1:4) at different concentrations (3% or 4%) and glycerol was used as plasticizer (1 or 2%). The films were thin (18-30 µm), translucent, flexible, and homogeneous. The surface pH was suitable for buccal application. All films reached high mechanical resistance and the mucoadhesive ability of them was evidenced. High ratio of gellan gum improved the mechanical resistance and the mucoadhesion of the films as well as the control of drug release rates. The films did not disintegrate in simulate saliva up to 24 h and curcumin release could be sustained up to 12 h. The set of data evidence that the films designed in this work represent a potential platform for buccal drug delivery.

Sedative and physiologic effects of tiletamine-zolazepam following buccal administration in cats.

OBJECTIVES: The aim of this study was to describe the sedative and some physiological effects of tiletamine-zolazepam following buccal administration (BA) in cats. METHODS: Seven healthy spayed European shorthair cats (three males, four females) were studied twice in this randomized, blinded, crossover study. Each cat received two doses of tiletamine-zolazepam by BA: the low-dose (LD) group consisted of 5 mg/kg of each drug, and the high-dose (HD) group consisted of 7.5 mg/kg of each. Baseline systolic blood pressure (SAP), heart rate (HR), respiratory rate (RR) and a sedation score were recorded prior to administration of each treatment. The same variables plus the percentage of hemoglobin saturated with oxygen as measured by pulse oximetry (SpO2) were recorded at predefined intervals for the next 2 h. RESULTS: All cats completed the study. No retching or vomiting were observed. Hypersalivation was observed in 0/7 and 3/7 for LD and HD groups, respectively (P = 0.2). There were significant changes in scores over time for posture, response to clippers and response to manual restraint for both groups, without differences between groups. RR, HR and SAP changed significantly over time. SAP and RR were significantly lower for the HD than for the LD group. No values for hemoglobin saturation <95% were observed. CONCLUSIONS AND RELEVANCE: BA of tiletamine-zolazepam at the doses studied here is a simple and effective method for chemical restraint in cats, where the LD group had a lower impact on SAP and RR than the HD group.

Transbuccal delivery of benznidazole associated with monoterpenes: permeation studies and mechanistic insights.

Benznidazole (BZN) represents the only drug currently available for the treatment of Chagas disease in most endemic countries. When administered orally, high doses are required due to its extensive hepatic metabolism and its toxicity represents the main reason for treatment withdrawals. Because of these complications, transbuccal administration of BZN was investigated. This route avoids the first-pass hepatic metabolism and presents high permeability, with direct access to the systemic circulation. BZN was applied on porcine buccal mucosa after pretreatment with pure eugenol, carvacrol or limonene. Thermal (DSC) and spectroscopic (FT-IR) analyzes were performed to investigate the mechanisms of drug absorption enhancement. The permeability coefficient values of BZN increased 2.6, 2.9 and 4.9-fold after pretreatment with eugenol, carvacrol and limonene, respectively. The lag time, in turn, was shortened in the pretreated samples. The DSC and FT-IR analyzes suggested that transport of BZN through the buccal mucosa is associated with log P and size of monoterpenes. Limonene, the most effective absorption enhancer, contributed to greater interaction with non-polar domains of the buccal epithelium. Overall, BZN showed to be efficiently transported through the buccal route, but in vivo pharmacokinetic studies should be performed to confirm these findings.

[Oral trans-mucosal dexmedetomidine for controlling of emergence agitation in children undergoing tonsillectomy: a randomized controlled trial]. / Dexmedetomidina transmucosa oral para controle da agitação ao despertar em crianças submetidas a amigdalectomia: ensaio clínico randomizado.

OBJECTIVES: Emergence agitation is a negative behavior commonly recorded after pediatric tonsillectomy. We investigated the efficacy of preoperative premedication with oral transmucosal buccal dexmedetomidine on the incidence and severity of emergence agitation in preschool children undergoing tonsillectomy under sevoflurane anesthesia. METHODS: Ninety patients aged (3-6 years), ASA I-II were enrolled into three groups (n = 30) to receive oral transmucosal dexmedetomidine 0.5 µg.kg-1 (Group DEX I), 1 µg.kg-1 (Group DEX II) or saline placebo (Group C). Our primary endpoint was the Watcha agitation score at emergence in PACU. Secondary outcomes were preoperative sedation score, intraoperative hemodynamics, postoperative Objective Pain Scale (OPS) and adverse effects. RESULTS: The patients' demographics, preoperative sedation scores and extubation time showed no difference between groups. Significant differences between groups in incidence and frequency distribution of each grade of Watcha score were evident at 5 minutes (p = 0.007), 10 minutes (p = 0.034), 30 minutes (p = 0.022), 45 minutes (p = 0.034) and 60 minutes (p = 0.026), postoperatively with significant differences between DEX I and II groups. DEX groups showed lower OPS scores at 5 minutes (p = 0.011), 10 minutes (p = 0.037) and 30 minutes (p = 0.044) after arrival at PACU, with no difference between DEX I and II groups. Patients in DEX II group exhibited lower intraoperative mean heart rate at 15 minutes (p = 0.020), and lower mean arterial pressure at 30 minutes, (p = 0.040), 45 minutes (p = 0.002) and 60 minutes (p = 0.006) with no significant differences between groups in other time points. CONCLUSION: This study demonstrates the clinical advantage and the simple technique of oral transmucosal DEX premedication for emergence agitation in preschool children undergoing tonsillectomy under sevoflurane anesthesia compared with saline placebo. TRIAL REGISTRATION: Clinical Trials.gov trial registry: NCT02720705.

Oral trans-mucosal dexmedetomidine for controlling of emergence agitation in children undergoing tonsillectomy: a randomized controlled trial / Dexmedetomidina transmucosa oral para controle da agitação ao despertar em crianças submetidas a amigdalectomia: ensaio clínico randomizado

Abstract Objectives: Emergence agitation is a negative behavior commonly recorded after pediatric tonsillectomy. We investigated the efficacy of preoperative premedication with oral transmucosal buccal dexmedetomidine on the incidence and severity of emergence agitation in preschool children undergoing tonsillectomy under sevoflurane anesthesia. Methods: Ninety patients aged (3-6 years), ASA I‒II were enrolled into three groups (n = 30) to receive oral transmucosal dexmedetomidine 0.5 µg.kg-1 (Group DEX I), 1 µg.kg-1 (Group DEX II) or saline placebo (Group C). Our primary endpoint was the Watcha agitation score at emergence in PACU. Secondary outcomes were preoperative sedation score, intraoperative hemodynamics, postoperative Objective Pain Scale (OPS) and adverse effects. Results: The patients' demographics, preoperative sedation scores and extubation time showed no difference between groups. Significant differences between groups in incidence and frequency distribution of each grade of Watcha score were evident at 5 minutes (p= 0.007), 10 minutes (p= 0.034), 30 minutes (p= 0.022), 45 minutes (p= 0.034) and 60 minutes (p= 0.026), postoperatively with significant differences between DEX I and II groups. DEX groups showed lower OPS scores at 5 minutes (p= 0.011), 10 minutes (p= 0.037) and 30 minutes (p= 0.044) after arrival at PACU, with no difference between DEX I and II groups. Patients in DEX II group exhibited lower intraoperative mean heart rate at 15 min (p= 0.020), and lower mean arterial pressure at 30 minutes, (p= 0.040), 45 minutes (p= 0.002) and 60 minutes (p= 0.006) with no significant differences between groups in other time points. Conclusion: This study demonstrates the clinical advantage and the simple technique of oral transmucosal DEX premedication for emergence agitation in preschool children undergoing tonsillectomy under sevoflurane anesthesia compared with saline placebo. Trial registration Clinical Trials.gov trial registry: NCT02720705.

Resumo Objetivos: A agitação ao despertar da anestesia é um comportamento negativo comumente registrado após amigdalectomia pediátrica. Avaliamos a eficácia da pré-medicação com dexmedetomidina via transmucosa oral no pré-operatório sobre a incidência e gravidade da agitação ao despertar em crianças pré-escolares submetidas à amigdalectomia sob anestesia com sevoflurano. Métodos: Noventa pacientes entre três e seis anos e estado físico ASA I-II foram incluídos em três grupos (n = 30) para receber 0,5 µg.kg-1 ou 1 µg.kg-1 de dexmedetomidina via transmucosa oral (Grupo DEX I e Grupo DEX II, respectivamente) ou solução salina (Grupo C). O desfecho primário foi o escore de agitação ao despertar medido com a escala de Watcha na SRPA. Os desfechos secundários foram escore de sedação pré-operatória, hemodinâmica intraoperatória, escore OPS (Objective Pain Scale) e efeitos adversos no pós-operatório. Resultados: A demografia dos pacientes, os escores de sedação pré-operatória e o tempo de extubação não apresentaram diferença entre os grupos. Diferenças significativas entre os grupos na distribuição da incidência e frequência de cada grau do escore de Watcha foram evidentes aos 5 minutos (p = 0,007), 10 minutos (p = 0,034), 30 minutos (p = 0,022), 45 minutos (p = 0,034) e 60 minutos (p = 0,026) no pós-operatório, com diferenças significativas entre os grupos DEX I e II. Os grupos DEX apresentaram escores OPS mais baixos aos 5 minutos (p = 0,011), 10 minutos (p = 0,037) e 30 minutos (p = 0,044) após a chegada à SRPA, sem diferença entre os grupos DEX I e II. Os pacientes do grupo DEX II apresentaram menor frequência cardíaca média aos 15 minutos de intraoperatório (p = 0,020) e menor pressão arterial média aos 30 minutos, (p = 0,040), 45 minutos (p = 0,002) e 60 minutos (p = 0,006), sem diferenças significativas entre os grupos em outros momentos. Conclusão: Este estudo demonstra a vantagem clínica e a técnica simples da pré-medicação com DEX por via transmucosa oral para agitação ao despertar em crianças pré-escolares submetidas à amigdalectomia sob anestesia com sevoflurano, comparado à solução salina. Registro do estudo: Clinical Trials.gov trial registry: NCT02720705.

Liposomal-based lidocaine formulation for the improvement of infiltrative buccal anaesthesia.

This study describes the encapsulation of the local anaesthetic lidocaine (LDC) in large unilamellar liposomes (LUV) prepared in a scalable procedure, with hydrogenated soybean phosphatidylcholine, cholesterol and mannitol. Structural properties of the liposomes were assessed by dynamic light scattering, nanoparticle tracking analysis and transmission electron microscopy. A modified, two-compartment Franz-cell system was used to evaluate the release kinetics of LDC from the liposomes. The in vivo anaesthetic effect of liposomal LDC 2% (LUVLDC) was compared to LDC 2% solution without (LDCPLAIN) or with the vasoconstrictor epinephrine (1:100 000) (LDCVASO), in rat infraorbital nerve blockade model. The structural characterization revealed liposomes with spherical shape, average size distribution of 250 nm and low polydispersity even after LDC incorporation. Zeta potential laid around -30 mV and the number of suspended liposomal particles was in the range of 1012 vesicles/mL. Also the addition of cryoprotectant (mannitol) did not provoke structural changes in liposomes properties. In vitro release profile of LDC from LUV fits well with a biexponential model, in which the LDC encapsulated (EE% = 24%) was responsible for an increase of 67% in the release time in relation to LDCPLAIN (p < 0.05). Also, the liposomal formulation prolonged the sensorial nervous blockade duration (∼70 min), in comparison with LDCPLAIN (45 min), but less than LDCVASO (130 min). In this context, this study showed that the liposomal formulations prepared by scalable procedure were suitable to promote longer and safer buccal anaesthesia, avoiding side effects of the use of vasoconstrictors.

Effect of drug incorporation technique and polymer combination on the performance of biopolymeric antifungal buccal films.

Numerous films with a dissolved or dispersed active principle within a polymeric matrix have been described in literature. However, the incorporation of solid crystals into the films may influence several relevant properties. Additionally, it has been reported that different polymeric matrices lead to films presenting a different performance. The aim of this work was to evaluate the effect of the combination of chitosan with carrageenan (κ-, λ-, and ι-) as matrices, and of the miconazole nitrate incorporation method, on the films behavior. Mechanical properties, drug release and antifungal activity were evaluated. The state of the drug in the films was analyzed by different techniques. Films showed a homogeneous surface and a thermal protective effect on the drug. The combination of chitosan and λ-carrageenan leads to films with the highest values of tensile and mucoadhesive strength. Films with solubilized drug displayed slightly higher elongation at break, tensile and mucoadhesive strength and faster drug release than those with suspended miconazole nitrate. However, no differences were found regarding the antifungal activity of the different formulations including time-to-kill curves.

Effect of Topical Erythropoietin (EPO) on palatal wound healing subsequent to Free Gingival Grafting (FGG).

Free gingival grafting, the most predictable technique to increase the keratinized gingiva, leaves an open wound on the palate and the resulting discomfort during the healing phase is a significant concern. This study was intended to evaluate the effect of topical erythropoietin on healing of the donor site. Twelve patients lacking an attached gingiva at two sites in the mandible were included. In the test group, 1 mL of gel containing erythropoietin at a concentration of 4,000 IU mL-1 was applied to the donor site, whereas the control group was treated with 2 mL of the gel alone. On the second day after surgery, the same procedure was repeated. H2O2 was used to evaluate the amount of epithelialization. Clinical healing was compared using photographs and direct examination. The EPO group showed significantly better keratinization only on day 21. Comparison of clinical healing based on direct examination revealed significantly better healing in the test group on day 28. Furthermore, inflammation in the test group was lower than in the control group on the same day. Topical application of EPO improves palatal wound healing during the third and fourth weeks after free gingival graft procedures.

The Effect of Inkjet Printing over Polymeric Films as Potential Buccal Biologics Delivery Systems.

The buccal mucosa appears as a promissory route for biologic drug administration, and pharmaceutical films are flexible dosage forms that can be used in the buccal mucosa as drug delivery systems for either a local or systemic effect. Recently, thin films have been used as printing substrates to manufacture these dosage forms by inkjet printing. As such, it is necessary to investigate the effects of printing biologics on films as substrates in terms of their physical and mucoadhesive properties. Here, we explored solvent casting as a conventional method with two biocompatible polymers, hydroxypropyl methylcellulose, and chitosan, and we used electrospinning process as an electrospun film fabrication of polycaprolactone fibers due to its potential to elicit mucoadhesion. Lysozyme was used as biologic drug model and was formulated as a solution for printing by thermal inkjet printing. Films were characterized before and after printing by mechanical and mucoadhesive properties, surface, and ultrastructure morphology through scanning electron microscopy and solid state properties by thermal analysis. Although minor differences were detected in micrographs and thermograms in all polymeric films tested, neither mechanical nor mucoadhesive properties were affected by these differences. Thus, biologic drug printing on films was successful without affecting their mechanical or mucoadhesive properties. These results open way to explore biologics loading on buccal films by inkjet printing, and future efforts will include further in vitro and in vivo evaluations.

Prophylactic Dextrose Gel Does Not Prevent Neonatal Hypoglycemia: A Quasi-Experimental Pilot Study.

OBJECTIVE: To test the hypothesis that prophylactic dextrose gel administered to newborn infants at risk for hypoglycemia will increase the initial blood glucose concentration after the first feeding and decrease neonatal intensive care unit (NICU) admissions for treatment of asymptomatic neonatal hypoglycemia compared with feedings alone. STUDY DESIGN: This quasi-experimental study allocated asymptomatic at-risk newborn infants (late preterm, birth weight <2500 or >4000 g, and infants of mothers with diabetes) to receive prophylactic dextrose gel (Insta-Glucose; Valeant Pharmaceuticals North America LLC, Bridgewater, New Jersey); other at-risk infants formed the control group. After the initial feeding, the prophylactic group received dextrose gel (0.5 mL/kg) rubbed into the buccal mucosa. The blood glucose concentration was checked 30 minutes later. Initial glucose concentrations and rate of NICU admissions were compared between the prophylactic group and controls using bivariate analyses. A multivariable linear regression compared first glucose concentrations between groups, adjusting for at-risk categories and age at first glucose concentration. RESULTS: There were 236 subjects (72 prophylactic, 164 controls). The first glucose concentration was not different between the prophylactic and control groups in bivariate analysis (52.1 ± 17.1 vs 50.5 ± 15.3 mg/dL, P = .69) and after adjusting for covariates (P = .18). Rates of NICU admission for treatment of transient neonatal hypoglycemia were 9.7% and 14.6%, respectively (P = .40). CONCLUSIONS: Prophylactic dextrose gel did not reduce transient neonatal hypoglycemia or NICU admissions for hypoglycemia. The carbohydrate concentration of Insta-Glucose (77%) may have caused a hyperinsulinemic response, or alternatively, exogenous enteral dextrose influences glucose homeostasis minimally during the first few hours when counter-regulatory mechanisms are especially active. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02523222.

Delivering Resveratrol on the Buccal Mucosa Using Mucoadhesive Tablets: A Potential Treatment Strategy for Inflammatory Oral Lesions.

BACKGROUND: Resveratrol is a polyphenol that has gained momentum in therapeutics in the last few years. OBJECTIVE: In this study, we hypothesised that resveratrol could act prophylactically and/or treat inflammatory lesions of the oral cavity after being delivered by two different formulations of buccal mucoadhesive tablets (F1 and F2, which differed in terms of viscosity agents used). METHODS: This hypothesis was assessed through permeation studies, to verify diffusion of the drug through the buccal mucosa using a porcine model to predict human in vivo behaviour. RESULTS: F2 (tablet with less viscosity agent) presented better permeation than F1, but the amount of drug that crossed the mucosa was still low compared to the amount retained within it (35.90 µg found in the receptor medium and 15.63 mg quantified within the mucosa). CONCLUSION: This accounted for a local effect rather than a systemic one, which is desirable for local processes, such as oral mucositis, lichen planus, erythema multiforme, nicotinic stomatitis, recurrent aphthous stomatitis, among others. In this sense, resveratrol-loaded mucoadhesive tablets appear to be a prominent alternative to prevent and/or cure inflammatory lesions of the oral cavity.

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.

Effect of Topical Erythropoietin (EPO) on palatal wound healing subsequent to Free Gingival Grafting (FGG)

Abstract Free gingival grafting, the most predictable technique to increase the keratinized gingiva, leaves an open wound on the palate and the resulting discomfort during the healing phase is a significant concern. This study was intended to evaluate the effect of topical erythropoietin on healing of the donor site. Twelve patients lacking an attached gingiva at two sites in the mandible were included. In the test group, 1 mL of gel containing erythropoietin at a concentration of 4,000 IU mL-1 was applied to the donor site, whereas the control group was treated with 2 mL of the gel alone. On the second day after surgery, the same procedure was repeated. H2O2 was used to evaluate the amount of epithelialization. Clinical healing was compared using photographs and direct examination. The EPO group showed significantly better keratinization only on day 21. Comparison of clinical healing based on direct examination revealed significantly better healing in the test group on day 28. Furthermore, inflammation in the test group was lower than in the control group on the same day. Topical application of EPO improves palatal wound healing during the third and fourth weeks after free gingival graft procedures.

Development and Evaluation of Buccal Films Based on Chitosan for the Potential Treatment of Oral Candidiasis.

In this work, chitosan films were prepared by a casting/solvent evaporation methodology using pectin or hydroxypropylmethyl cellulose to form polymeric matrices. Miconazole nitrate, as a model drug, was loaded into such formulations. These polymeric films were characterized in terms of mechanical properties, adhesiveness, and swelling as well as drug release. Besides, the morphology of raw materials and films was investigated by scanning electron microscopy; interactions between polymers were analyzed by infrared spectroscopy and drug crystallinity studied by differential scanning calorimetry and X-ray diffraction. In addition, antifungal activity against cultures of the five most important fungal opportunistic pathogens belonging to Candida genus was investigated. Chitosan:hydroxypropylmethyl cellulose films were found to be the most appropriate formulations in terms of folding endurance, mechanical properties, and adhesiveness. Also, an improvement in the dissolution rate of miconazole nitrate from the films up to 90% compared to the non-loaded drug was observed. The in vitro antifungal activity showed a significant activity of the model drug when it is loaded into chitosan films. These findings suggest that chitosan-based films are a promising approach to deliver miconazole nitrate for the treatment of candidiasis.

Comparison between two antimicrobial protocols with or without guided bone regeneration in the treatment of peri-implantitis. A histomorphometric study in dogs.

OBJECTIVES: This study used a dog model to evaluate two antimicrobial protocols with or without guided bone regeneration (GBR) in the surgical reconstruction of peri-implantitis defects. MATERIAL AND METHODS: Eight beagle dogs subject to ligature-induced peri-implantitis were used. The animals either received antimicrobial photodynamic therapy or topical tetracycline hydrochloride combined with GBR or as stand-alone surgical interventions. Block biopsies of the defect sites for histological analysis were obtained at euthanasia, 12 weeks postsurgery. The primary outcome of the study was re-osseointegration; secondary outcomes included alveolar bone gain and remaining defect characteristics. The effects of the implant site, early exposure, and type of antimicrobial protocol on bone regeneration were also evaluated. RESULTS: No significant differences were observed between the two antimicrobial protocols, and the adjunctive use of GBR failed to significantly improve re-osseointegration or bone gain using either protocol. Buccal sites and implant early exposure negatively affected bone regeneration. CONCLUSION: Both antimicrobial therapies stand-alone or combined with GBR allowed similar and limited bone gain.