Mucoadhesive Devices Research Articles

Mucoadhesive Electrospun Fibre-Based Technologies for Oral Medicine.

Oral disease greatly affects quality of life, as the mouth is required for a wide range of activities including speech, food and liquid consumption. Treatment of oral disease is greatly limited by the dose forms that are currently available, which suffer from short contact times, poor site specificity, and sensitivity to mechanical stimulation. Mucoadhesive devices prepared using electrospinning offer the potential to address these challenges by allowing unidirectional site-specific drug delivery through intimate contact with the mucosa and with high surface areas to facilitate drug release. This review will discuss the range of electrospun mucoadhesive devices that have recently been reported to address oral inflammatory diseases, pain relief, and infections, as well as new treatments that are likely to be enabled by this technology in the future.

Autoassemblies of α-Cyclodextrin and Grafted Polysaccharides: Crystal Structure and Specific Properties of the Platelets.

Cyclodextrins (CDs) are a family of oligosaccharides with a toroid shape, which exhibit a remarkable ability to include guest molecules in their internal cavity, providing a hydrophobic environment for poorly soluble molecules. Recently, new types of inclusions of α CDs with alkyl grafted polysaccharide chains (pullulan, chitosan, dextran, amylopectin, chondroitin sulfate...) have been prepared which are autoassembled into micro- and nanoplatelets. We report in this paper an extensive investigation of platelets with different compositions, including their reversible hydration (thermogravimetric analysis), crystalline structure (powder X-ray diffraction), dimensions and shapes (scanning electron microscopy-field emission gun), thermal properties, solubility, and melting (micro-differential scanning calorimetry). The crystalline platelets exhibit layered structures intercalating the polysaccharide backbones and CD complexes hosting the grafted alkyl chains. The monoclinic symmetry of columnar-type crystals suggests a head-to-tail arrangement of the CDs. The platelets have a preferentially hexagonal shape with sharp edges, variable sizes, and thicknesses and sometimes show incomplete layers (terraces). The crystal parameters change upon dehydration. Melting temperatures of platelets in aqueous solutions exceed 100 °C. Finally, we discuss the potential relation between the platelet structure and applications for mucoadhesive devices.

Intestinal mucoadhesive devices for oral delivery of insulin.

Oral delivery of proteins such as insulin has been a long‐lasting challenge owing to gastrointestinal degradation and poor permeability of therapeutic macromolecules across biological membranes. We have developed mucoadhesive intestinal devices for oral delivery of insulin to address this challenge. Here we demonstrate a combination of intestinal devices and a permeation enhancer, dimethyl palmitoyl ammonio propanesulfonate (PPS), for oral delivery of insulin. The devices were delivered from a capsule coated with a pH‐responsive enteric coating. The devices adhere to intestinal mucosa, release their protein load unidirectionally, and prevent enzymatic degradation in the gut. Devices were found to completely release their drug load within 3–4 hr and showed excellent strength of mucoadhesion to porcine intestine. Devices loaded with insulin and PPS significantly decreased blood glucose levels by 30 and 33% in diabetic and nondiabetic rats, respectively. These studies demonstrate that intestinal mucoadhesive devices are a promising oral alternative to insulin injections and therefore should be further explored for the treatment of diabetes.

Delivery of Exenatide and Insulin Using Mucoadhesive Intestinal Devices

A major disadvantage associated with current diabetes therapy is dependence on injectables for long-term disease management. In addition to insulin, incretin hormone replacement therapies including exenatide have added a new class of drugs for Type-2 diabetes. Although efficacious, patient compliance with current diabetic therapy is poor due to requirement of injections, inability to cross the intestinal epithelium and instability in the gastrointestinal tract. Here, we report the efficacy of a mucoadhesive device in providing therapeutic concentrations of insulin and exenatide via oral administration. Devices were prepared with a blend of FDA-approved polymers, carbopol, pectin and sodium carboxymethylcellulose, and were tested for drug carrying capability, in vitro release, Caco-2 permeability, and in vivo efficacy for insulin and exenatide. Results suggested that mucoadhesive devices successfully provided controlled release of FITC-insulin, released significant amounts of drug, while providing noteworthy enhancement of drug transport across Caco-2 monolayers without compromising monolayer integrity. In-vivo administration of the devices provided significant enhancement of drug absorption with 13- and 80-fold enhancement of relative bioavailability for insulin and exenatide compared to intestinal injections with significant increase in half-lives, thus resulting in prolonged blood glucose reduction. This study validates the efficacy of mucoadhesive devices in promoting oral peptide delivery to improve patient compliance and dose adherence.

Polycationic elastin-like recombinamer as a mucoadhesive device

Polycationic elastin-like recombinamer as a mucoadhesive device

Mucoadhesive intestinal devices for oral delivery of salmon calcitonin

One of the major challenges faced by therapeutic polypeptides remains their invasive route of delivery. Oral administration offers a potential alternative to injections; however, this route cannot be currently used for peptides due to their limited stability in the stomach and poor permeation across the intestine. Here, we report mucoadhesive devices for oral delivery that are inspired by the design of transdermal patches and demonstrate their capabilities in vivo for salmon calcitonin (sCT). The mucoadhesive devices were prepared by compressing a polymeric matrix containing carbopol, pectin and sodium carboxymethylcellulose (1:1:2), and were coated on all sides but one with an impermeable and flexible ethyl cellulose (EC) backing layer. Devices were tested for in vitro dissolution, mucoadhesion to intestinal mucosa, enhancement of drug absorption in vitro (Caco-2 monolayer transport) and in vivo in rats. Devices showed steady drug release with ≈75% cumulative drug released in 5h. Devices also demonstrated strong mucoadhesion to porcine small intestine to withstand forces up to 100 times their own weight. sCT-loaded mucoadhesive devices exhibited delivery of sCT across Caco-2 monolayers and across the intestinal epithelium in vivo in rats. A ≈52-fold (pharmacokinetic) and ≈44-fold (pharmacological) enhancement of oral bioavailability was observed with mucoadhesive devices when compared to direct intestinal injections. Oral delivery of devices in enteric coated capsules resulted in significant bioavailability enhancement.

Mucoadhesive drug delivery system: An overview

Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time of the dosage form at the site of absorption. The drugs which have local action or those which have maximum absorption in gastrointestinal tract (GIT) require increased duration of stay in GIT. Thus, mucoadhesive dosage forms are advantageous in increasing the drug plasma concentrations and also therapeutic activity. In this regard, this review covers the areas of mechanisms and theories of mucoadhesion, factors influencing the mucoadhesive devices and also various mucoadhesive dosage forms.

Micro- and nanofabrication methods in nanotechnological medical and pharmaceutical devices

Micro- and nanofabrication techniques have revolutionized the pharmaceutical and medical fields as they offer the possibility for highly reproducible mass-fabrication of systems with complex geometries and functionalities, including novel drug delivery systems and bionsensors. The principal micro- and nanofabrication techniques are described, including photolithography, soft lithography, film deposition, etching, bonding, molecular self assembly, electrically induced nanopatterning, rapid prototyping, and electron, X-ray, colloidal monolayer, and focused ion beam lithography. Application of these techniques for the fabrication of drug delivery and biosensing systems including injectable, implantable, transdermal, and mucoadhesive devices is described.

Oramucosal delivery of LHRH: pharmacokinetic studies of controlled and enhanced transmucosal permeation.

Several transmucosal therapeutic systems (TmTs) were developed to study the enhanced/controlled delivery of luteinizing hormone-releasing hormone (LHRH) through oral mucosae for prolonged periods. TmTs is a track field-shaped bilayer mucoadhesive device consisting of fast-release and sustained-release layers. In vivo evaluations were performed in beagle dogs, and pharmacokinetic profiles were monitored to characterize the transmucosal permeation kinetics of LHRH delivered by the various TmTs formulations containing a stabilizer, cetylpyridinium chloride, and a permeation enhancer, such as bile salts, to enhance the stability and permeability of LHRH. The plasma LHRH concentrations were observed to reach the plateau level within 30 min and were maintained for 2 hr following application of TmTs, in contrast to a rapid elimination profile observed after IV administration. Addition of 5% bile salt into the fast-release layer was observed to produce an enhancement in the absorption rate, higher plateau plasma levels, and greater systemic bioavailability. Addition of pH modifiers was noted to affect the bile salt enhanced transmucosal delivery of LHRH. To prolong the plasma LHRH level, several loading doses of LHRH were incorporated into the sustained-release layer. The plasma levels were sustained and the area under the curve (AUC) values were found to be linearly dependent upon the combined loading doses of LHRH in the fast-release and sustained-release layers. Mucosal irritation was also measured, using buccal mucosa, and results were observed to be low and reversible for the single application. The results indicated that TmTs is relatively safe and capable of achieving enhanced and controlled transmucosal delivery of peptide drugs.

Development of Anticandidal Delivery Systems: (II) Mucoadhesive Devices for Prolonged Drug Delivery in the Oral Cavity

AbstractConventional dosage forms designed for drug delivery in the oral cavity suffer from the disadvantage of an initial burst of activity followed by a rapid decrease in concentration to subtherapeutic levels. To counter this effect, two prolonged-release dosage forms were devised for the treatment of oral candidiasis. These devices were to contain the antifungals, chlorhexidine and clotrimazole, for therapy against Candida albicans, and also benzocaine and hydrocortisone to combat the pain and inflammation secondaly to a candidal infection. Release studies demonstrated that only chlorhexidine and clotrimazole could be delivered in a controlled manner from the mucoadhesive patches. On the other hand, release of all four drugs could be controlled from the mucoadhesive tablets, with optimum release of the drugs in 24 hr achieved using sodium carboxymethylcellulose and polyethylene oxide (85:15) combination tablets.

Oral mucosa controlled delivery of LHRH by bilayer mucoadhesive polymer systems

Several mucoadhesive devices have been developed from mucoadhesive polymers for the enhanced and controlled transmucosal delivery of LHRH through oral mucosa. The mucoadhesive devices developed are of a bilayer type, which consist of a fast-release layer containing PVP (k-30), and a sustained-release layer formulated from Carbopol 934 and PVP (k-90). They have been designed for a prolonged application onto the gingival/ alveolar mucosa for a period of up to 24 h. These oral mucosa LHRH delivery devices also contain enhancer, sodium cholate, to promote the transmucosal permeation of LHRH and stabilizer, cetylpyridinium chloride, to stabilize LHRH from degradation by the microflora. In order to simulate the in vivo condition, a specially designed device holder was also used to have one side of the mucoadhesive device adhering to the alveolar mucosa and the other side facing the buccal mucosa. Results from the release kinetics studies demonstrated a burst release of LHRH from the fast-release layer, which provide a rapid delivery of LHRH, and a prolonged release of LHRH from the sustainedrelease layer, which maintains a sustained delivery of LHRH. Permeation kinetics studies indicated that the transmucosal permeation of LHRH increases as increasing the loading dose of either LHRH or enhancer in the fast-release layer, but decreases as increasing the ratio of Carbopol 934/PVP (k-90) in the sustained-release layer. The formulation of the mucoadhesive device can be varied to achieve a specific rate of transmucosal permeation.