Oral local drug delivery and new perspectives in oral drug formulation

Modern pharmaceutical science has provided us with a wide range of substances to be administered with a wide large variety of dosage forms. Local drug delivery systems have been used for a long time; in particular, for the local therapy of diseases affecting the oral cavity. Although these diseases are often extremely responsive to local therapy, the mouth often presents various difficulties in the application of topical compounds (owing to saliva and the mouth's different functions), resulting in a short retention time of dosage forms with a consequent low therapeutic efficacy. To resolve these limitations, research today concentrates on the development of bioadhesive formulations. This re…

Recent Advances in Drug Delivery from the Oral Cavity. Focus on innovative buccal drug delivery devices

In this report, the drug administration via the oral cavity is discussed. Regional variations in oral mucosae, drug delivery via the keratinised mucosae for local treatment, and drug delivery via the not keratinised mucosae for local and systemic treatments are analyzed, focusing on Buccal drug delivery devices. Finally the IntelliDrug Device is presented as a revolutionary delivery system.

Formulazione di sistemi innovativi per la somministrazione di antitumorali per il trattamento del Carcinoma Orale Squamoso

Carico precoce su overdenture, valutazione a cinque anni.

Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three-Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile Delivery by Drug-Loaded Matrix Tablets

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal …

Evaluation of Galantamine transbuccal absorption by reconstituted human oral epithelium and porcine tissue as buccal mucosa models: Part I

Over the last decade, interest in delivering drugs through buccal mucosa has increased. As a major limitation in buccal drug delivery could be the low permeability of the epithelium, the aim of this study was to evaluate the aptitude of galantamine, useful in Alzheimer's disease, to penetrate the buccal mucosa. The evaluation of the ability of galantamine to permeate through the buccal epithelium was investigated using two permeation models. Firstly, in vitro permeation experiments were carried out using reconstituted human oral non-keratinised epithelium and Transwell diffusion cells system. Results were validated by ex vivo experiments using porcine buccal mucosa as membrane and Franz typ…

Efficacy and safety of an intraoral electrostimulation device for xerostomia relief: a multicenter, randomized trial.

Objective To evaluate the efficacy and safety of an intraoral electrostimulation device, consisting of stimulating electrodes, an electronic circuit, and a power source, in treating xerostomia. The device delivers electrostimulation through the oral mucosa to the lingual nerve in order to enhance the salivary reflex. Methods The device was tested on a sample of patients with xerostomia due to Sjogren's syndrome and other sicca conditions in a 2-stage prospective, randomized, multicenter trial. Stage I was a double-blind, crossover stage designed to compare the effects of the electrically active device with the sham device, each used for 1 month, and stage II was a 3-month open-label stage d…

Amiloidosi AL e mieloma multiplo:un raro caso di primaria manifestazione a livello della cavità orale e periorale

Novel non-invasive Adjunctive Techniques for Early Oral Cancer Diagnosis and Oral Lesions Examination

Oral cancer is a potentially fatal disease with an increasing incidence and an unchanged 5-year mortality rate. Unfortunately, oral cancer is often still late diagnosed, which leads to an increase in the likelihood of functional impairment due to treatment and mortality rate. Definitive diagnosis of oral cancer must be confirmed by scalpel biopsy and histological assessment. However despite its benefits, scalpel biopsy is invasive and it is burdened by a potential morbidity. Furthermore, previous studies have suggested a high degree of intraobserver and interobserver variability regarding the histological evaluation of malignancy. As a consequence, in recent years there has been a growing a…

Association of oral lichen planus with thyroid disease in a Finnish population: A retrospective case-control study: "A different finding from a Mediterranean area".

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Bioavailability in vivo of naltrexone following transbuccal administration by an electronically-controlled intraoral device: a trial on pigs.

Naltrexone (NLX), an opioid antagonist, is widely used in the treatment of opiate addiction, alcoholism and smoking cessation. Its current peroral administration induces various adverse side effects and has limited efficacy since bioavailability and patient compliance are poor. The development of a long-acting drug delivery system of NLX may overcome the current drawbacks and help in the improvement of treatment of addiction. The primary endpoints of this study were: a) to compare the NLX bioavailability and pharmacokinetics after delivering a single transbuccal dose, released by a prototype of intraoral device, versus an intravenous (I.V.) bolus of the same drug dose; b) to verify the func…

Stomatite aftosa ricorrente: studio retrospettivo di fattori eziologici. (Poster P56).

Demographic and behavioural profiles of patients with common oral mucosal lesions by a homogeneity analysis

Oral Diseases (2012) 18, 396–401 Objective:  The aim of this study is to assess the main oral mucosal lesions (OMLs) within a hospital base and to provide an anamnestic, diagnostic model based on homogeneity analysis of some variables. Methods:  The demographic and behavioural data (i.e. gender, age, smoking status, alcohol consumption and therapeutic drug usage) of 1753 patients with at least one OML were considered. Multiple correspondence analysis (MCA) and multivariate tests of the simultaneous marginal homogeneity hypothesis (SMH) were used to analyse the evidence of any differences between the demographic and behavioural profiles relating to OMLs diagnoses. Statistical significance of…

Controlled delivery of naltrexone by an intraoral device: in vivo study on human subjects.

Naltrexone is widely used in the treatment of opiate addiction but its current peroral administration is characterized by low bioavailability with various side effects. The development of a long-acting transbuccal delivery device (IntelliDrug) for NLX may be useful to improve patient compliance and the therapy effectiveness. The aims of the study are (a) to test basic safety and effectiveness of controlled transbuccal drug delivery on human subjects; (b) to compare NLX bioavailability following transbuccal delivery vs per os conventional delivery; and (c) to test the hypothesis that transbuccal delivery is more efficient than the conventional route. In this randomized cross-over pilot study…

Carbamazepine transbuccal delivery: the histo-morphological features of reconstituted human oral epithelium and buccal porcine mucosae in the transmucosal permeation.

Transbuccal drug delivery is an attractive way of administration since several well-known advantages are provided, especially with respect to peroral management. Carbamazepine (CBZ) is an anticonvulsant which is useful in controlling neuropathic pain, and it is currently administered by peroral route, although its absorption and bioavailability is limited due to various factors. The oral cavity could be an interesting site for transbuccal CBZ delivery due to two properties: slow administration of constant low drug doses and less dose-related side effects. However, in transbuccal absorption a major limitation could be the low permeability of the mucosa which results in low drug bioavailabil…

5-Fluorouracil Buccal Tablets for Locoregional Chemotherapy of Oral Squamous Cell Carcinoma: Formulation, Drug Release and Histological Effects on Reconstituted Human Oral Epithelium and Porcine Buccal Mucosa

5-Fluorouracil (5-FU) is currently used for treatment of oral squamous cell carcinoma (OSCC). 5-FU is given by i.v. although the systemic administration is associated with severe toxic effects and no topical formulations of 5-FU for buccal drug delivery have been reported. In this study we would report the development of buccal tablets suitable for direct application of low-doses of 5-FU on cancer lesions. The topical administration could be effective on tumor area while systemic undesired side effects are avoided. Preliminarily, the limited tendency of 5-FU to cross the buccal tissue was established using reconstituted human oral epithelium (RHOE, in vitro) and porcine buccal mucosa (ex vi…

Medium-term Culture of Normal Human Oral Mucosa: A Novel Three-dimensional Model to Study the Effectiveness of Drugs Administration

Tissue-engineered oral mucosal equivalents have been developed for in vitro studies for a few years now. However, the usefulness of currently available models is still limited by many factors, mainly the lack of a physiological extracellular matrix (ECM) and the use of cell populations that do not reflect the properly differentiated cytotypes of the mucosa of the oral cavity. For this reason, we have developed a novel three-dimensional culture model reflecting the normal architecture of the human oral mucosa, with the main aim of creating a better in vitro model where to test cellular responses to drugs administration. This novel 3D cell culture model (3D outgrowth) was set up using an arti…

Analisi proteomica della saliva mediante SELDI-TOF-MS per la diagnosi di carcinoma orale: risultati preliminari

PRELIMINARY ANALYSES FROM A HOSPITAL BASED STUDY ON 3154 WESTERN SICILIAN PATIENTS WITH ORAL MUCOSAL LESIONS

Objectives: Diagnosis of the wide variety of lesions that occur in the oral cavity is an essential part of dental practice. The objective of this study was to explore the demographic and behavioural profiles of patients affected by oral cavity diseases on a wide spectrum. Methods: Demographic and behavioural data of 3154 patients with at least one oral cavity disease among those consecutively visited between 2004 and 2009 at the Unit of Oral Medicine, were recorded: gender, age, smoking status, alcohol consumption, drugs use. Analysis was restricted to the eleven more frequent oral cavity diseases. Firstly, Multiple Correspondence Analysis (MCA) was applied as a descriptive tool to geometri…

Behçet's disease in an adolescent patient.

MEDIUM-TERM CULTURE OF THE NORMAL ORAL MUCOSA: A NOVEL THREE-DIMENSIONAL MODEL TO STUDY THE EFFECTIVENESS OF DRUGS ADMINISTRATION

Long-standing oral ulcers: proposal for a new `S-C-D classification system’

Persistent oral ulcers and erosions can be the final common manifestation, sometimes clinically indistinguishable, of a diverse spectrum of conditions ranging from traumatic lesions, infectious diseases, systemic and local immune-mediated lesions up to neoplasms. The process of making correct diagnosis for persistent oral ulcers still represents a challenge to clinicians. Major diagnostic criteria should include the clinical appearance of both ulcer and surrounding non-ulcerated mucosa, together with the evaluation of associated signs and symptoms, such as: number (single or multiple), shape, severity of the ulcer(s), conditions of remaining mucosa (white, red or with vesiculo-bullous lesio…

Oral HPV Infection: Current Strategies for Prevention and Therapy

Infection with High Risk (HR) Human Papillomaviruses (HPVs) is the main aetiological agent of Cervical Squamous Cell Carcinoma (CSCC) and also associated in a subgroup of other neoplasms, including Oropharyngeal Squamous cell Carcinoma (OPSCC). HPV infection, in genital as in oral mucosa, can also be subclinical or associated with benign proliferative lesions (common warts, condylomas, papillomas) caused mostly by infection with Low Risk (LR)-HPVs. In the last decades, extensive research has resulted in growing knowledge on HPV biology and specifically viral life cycle, biochemical properties of viral proteins and their interaction with the host proteins leading to potential new targets of …

New Prospectives in the Delivery of Galantamine for Elderly Patients Using the IntelliDrug Intraoral Device: In Vivo Animal Studies

The transbuccal delivery of drugs could assist several categories of chronic, especially elderly, patients in adhering to a correct dosage regimen. In particular, patients suffering from dementia have several difficulties in following the prescribed dosage, in addition to problems associated with swallowing tablets. Galantamine is currently used for treating patients with mild to moderate Alzheimer's-type dementia. The transbuccal delivery of this drug could be an interesting non- invasive and safe administration route. Several studies have been performed in vitro and ex vivo within the framework of a European Commission funded Project (IntelliDrug-FP6), aimed at developing a device which w…

Intraoral electrostimulator for xerostomia relief: a long-term, multicenter, open-label, uncontrolled, clinical trial

Objective A previous sham-controlled multinational study demonstrated the short-term efficacy and safety for xerostomia treatment of an intraoral device that delivers electrostimulation to the lingual nerve. The objective of this study was to test the hypothesis that those beneficial effects would be sustained over an 11-month period. Study Design The device was tested on a mixed sample of 94 patients with xerostomia in an open-label, uncontrolled, prospective multicenter trial. Statutory outcome assessments were done at 5th, 8th, and 11th months and analyzed by multiple comparisons. Results Improvements achieved at month 5 from baseline were sustained throughout the follow-up period for th…

Buccal delivery in treatment of Alzheimer disease: enhancement of galantamine absorption

Long-standing oral ulcers: proposal for a new 'S-C-D classification system': Authors' reply

Human buccal mucosa as an innovative site of drug delivery.

The authors review the ultra-structural aspects and permeability features of normal human oral mucosa, after having recently tested and used it as a new site of systemic drug delivery. The pertinent scientific literature from 1975 through 2009 has been analysed and discussed. Buccal epithelium is a relatively permeable, robust non-keratinized tissue and blood vessels drain directly into the jugular vein; due to its particular features, it has been of increasing interest to researchers as an alternative site of drug administration. The review describes the structure and function of the buccal mucosa, the rationale for transbuccal drug delivery and the main transmucosal drug delivery systems.…

Topical therapies for oral lichen planus management and their efficacy: a narrative review.

Oral Lichen Planus (OLP) is a chronic inflammatory condition implicating T cell-mediated cytotoxicity, and involving oral mucosal surfaces. Several therapeutic regimens have been evaluated to treat OLP and pain related, but often without high level of evidence. Topical formulations are the favourite for the majority of cases; bioadhesive formulations have been considered very useful and practical for local drug delivery in oral mucosa, due to the increased residence time on the oral mucosa of the dosage forms and better therapeutic efficacy. In this narrative review, authors try to illustrate the current topical managements for OLP from the accessible literature on this topic. Steroids are …

Direct visualization of oral-cavity tissue fluorescence as novel aid for early oral cancer diagnosis and potentially malignant disorders monitoring.

Direct visualization of the oral tissue autofluorescence has been recently reviewed in several studies as a possible adjunctive tool for early recognition and diagnosis of potentially malignant and malignant oral disorders. The aims of this study were to assess: a) the value of a simple handheld device for tissue auto-fluorescence visualization of potentially malignant oral lesions; and b) the sensitivity, specificity and diagnostic accuracy of tested device, using histological examination as the gold standard. 175 consecutive patients, with at least one clinical oral lesion, were enrolled in the study. Clinical conventional inspections were performed for each patient by two blind operator…

Long-standing oral ulcers: proposal for a new ‘S-C-D classification system’: Authors’ reply

Mucoadhesive polymers for oral transmucosal drug delivery: a review.

The oral mucosa offers an interesting site for the application of dosage forms that release drugs within/throughout the oral mucosa, by assuring a high drug bioavailability for topic and systemic effects. However, the relative permeability of the oral mucosa and the washing effect related to the oral fluids and mechanical stresses must be considered in the formulation of oral dosage forms. Since a sustained drug release can be guaranteed only if dosage forms remain in contact with the oral site of absorption/application for a prolonged time, the development of mucoadhesive dosage forms is mandatory. The mucoadhesion is a complex phenomenon and the mucoadhesive bond consists of two different…

Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three- Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile Delivery by Drug-Loaded Matrix Tablets

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal …

Long-Standing oral ulcers: proposal for a new S-C-D classification system'

Persistent oral ulcers and erosions can be the final common manifestation, sometimes clinically indistinguishable, of a diverse spectrum of conditions ranging from traumatic lesions, infectious diseases, systemic and local immune-mediated lesions up to neoplasms. The process of making correct diagnosis for persistent oral ulcers still represents a challenge to clinicians. Major diagnostic criteria should include the clinical appearance of both ulcer and surrounding non-ulcerated mucosa, together with the evaluation of associated signs and symptoms, such as: number (single or multiple), shape, severity of the ulcer(s), conditions of remaining mucosa (white, red or with vesiculo-bullous lesio…

Somministrazione transbuccale vs somministrazione endovenosa della Galantamina: studio sperimentale in vivo