Formulation and evaluation of floating mucoadhesive alginate beads for targetingHelicobacter pylori

Objectives: There are various obstacles in the eradication of Helicobacter.pylori (H. pylori) infections, including low antibiotic levels and poor accessibility of the drug at the site of the infection. This study describes the preparation and characterisation of novel floating-mucoadhesive alginate beads loaded with clarithromycin (CMN) for delivery to the gastric mucosa to improve the eradication of this micro-organism. Methods: Calcium alginate beads were prepared by ionotropic gelation. The formulation was modified through addition of oil and coating with chitosan in order to improve floating, mucoadhesion and modify drug release. Key findings: SEM confirmed the sphericity of the beads with X-ray microtomography (XμMT) showing the 3D structure of the beads with the layered internal structure of the bead and the even distribution of the drug within the bead. This formulation combined two gastro-retentive strategies and these formulations produced excellent in vitro floating, mucoadhesive and drug release characteristics. Enhanced stability of the beads in phosphate buffer raises a potential for the modified formulations to be targeted to regions of higher pH within the gastrointestinal tract with a higher pH. Drug release from these beads was sustained through an unstirred mucin layer simulating in vivo conditions under which the H. pylori resides in the gastric mucosa. Conclusions: This novel formulation will ensure retention for a longer period in the stomach than conventional formulations and control drug release, ensuring high local drug concentrations, leading to improved eradication of the bacteria

Development of Chitosan/Gelatin/Keratin Composite Containing Hydrocortisone Sodium Succinate as a Buccal Mucoadhesive Patch to Treat Desquamative Gingivitis

The aim of this research was to develop chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate as a buccal mucoadhesive patch to treat desquamative gingivitis, which was fabricated through an environmental friendly process. Mucoadhesive films increase the advantage of higher efficiency and drug localization in the affected region. In this research, mucoadhesive films, for the release of hydrocortisone sodium succinate, were prepared using different ratios of chitosan, gelatin and keratin. In the first step, chitosan and gelatin proportions were optimized after evaluating the mechanical properties, swelling capacity, water uptake, stability, and biodegradation of the films. Then, keratin was added at different percentages to the optimum composite of chitosan and gelatin together with the drug. The results of surface pH showed that none of the samples were harmful to the buccal cavity. FTIR analysis confirmed the influence of keratin on the structure of the composite. The presence of a higher amount of keratin in the composite films resulted in high mechanical, mucoadhesive properties and stability, low water uptake and biodegradation in phosphate buffer saline (pH = 7.4) containing 104 U/ml lysozyme. The release profile of the films ascertained that keratin is a rate controller in the release of the hydrocortisone sodium succinate. Finally, chitosan/gelatin/keratin composite containing hydrocortisone sodium succinate can be employed in dental applications

Polysaccharide food matrices for controlling the release, retention and perception of flavours

Polysaccharides have many roles across both the food and pharmaceutics industries. They are commonly used to enhance viscosity, stabilise emulsions and to add bulk to food products. In the pharmaceutics industry, they are also utilised for their mucoadhesive nature. Mucoadhesive polysaccharides can facilitate retention of active ingredients at mucosal sites for a prolonged time and formulations can be designed to control their release and bioavailability. This study investigates how polysaccharides, with differing physicochemical properties (e.g. functional groups and molecular weight), affect the release and perception of flavour compounds from films. Polysaccharide films were prepared using either high or low viscosity carboxymethyl cellulose, pullulan or hydroxypropyl methylcellulose. Glucose, vanillin or a combination of both was also added to the films to assess the effect of flavour release and perception over time. The films were assessed for glucose release in vitro, swelling and disintegration times, and mucoadhesive ability. Results show that flavour release and perception depend on the polysaccharide matrix properties; this includes how quickly the films dissolves, the rate of release of tastant compounds, and the mucoadhesive strength of the polysaccharide. A higher viscosity and slower disintegration time resulted in slower release of glucose in vitro and flavour perception in vivo

Freeze-dried mucoadhesive polymeric system containing pegylated lipoplexes : towards a vaginal sustained released system for siRNA

peer reviewedTopical vaginal sustained delivery of siRNA presents a significant challenge due to the short residence time of formulations. Therefore, a drug delivery system capable to adhere to the vaginal mucosa is desirable, as it could allow a prolonged delivery and increase the effectiveness of the therapy. The aim of this project is to develop a polymeric solid mucoadhesive system, loaded with lipoplexes, able to be progressively rehydrated by the vaginal fluids to form a hydrogel and to deliver siRNA to vaginal tissues. To minimize adhesive interactions with vaginal mucus components, lipoplexes were coated with different derivatives of polyethylene glycol: DPSE-PEG2000, DPSE-PEG750 and ceramide-PEG2000. Based on stability and diffusion properties in simulated vaginal fluids, lipoplexes containing DSPE-PEG2000 were selected and incorporated in hydroxyethyl cellulose (HEC) hydrogels. Solid systems, called sponges, were then obtained by freeze-drying. Sponges meet acceptable mechanical characteristics and their hardness, eformability and mucoadhesive properties are not influenced by the presence of lipoplexes. Finally, mobility and stability of lipoplexes inside sponges rehydrated with vaginal mucus, mimicking in situ conditions, were evaluated by advanced fluorescence microscopy. The release rate was found to be influenced by the HEC concentration and consequently by the viscosity after rehydration. This study demonstrates the feasibility of entrapping pegylated lipoplexes into a solid matrix system for a prolonged delivery of siRNA into the vagina

Chitosan/Poly(2-ethyl-2-oxazoline) films with ciprofloxacin for application in vaginal drug delivery

Chitosan (CHI) and chitosan/poly(2-ethyl-2-oxazoline) (CHI/POZ)-based films were prepared by casting from aqueous solutions of polymer blends with different compositions. Ciprofloxacin was used as a model drug in these formulations. The weight, thickness, folding endurance and transparency of blend films were measured and characterised. All films had a uniform thickness (0.06 ± 0.01 mm) and exhibited sufficient flexibility. The surface pHs of films ranged from 3.76 ± 0.49 to 4.14 ± 0.32, which is within the pH range suitable for vaginal applications. The cumulative release of the drug from the films in experiments in vitro was found to be 42 ± 2% and 56 ± 1% for pure CHI and CHI/POZ (40:60) films, respectively. Drug-free chitosan/poly(2-ethyl-2-oxazoline) films showed weak antimicrobial activity against Escherichia coli. Drug-loaded CHI and CHI/POZ films showed good antimicrobial properties against both Gram-positive Staphylococcus aureus and Gram-negative bacteria Escherichia coli. Mucoadhesive properties of these films with respect to freshly excised sheep vaginal mucosa were evaluated using a tensile method. It was established that all films were mucoadhesive, but an increase in POZ content in the blend resulted in a gradual reduction of their ability to stick to vaginal mucosa. These films could potentially find applications in vaginal drug delivery

Chitosan-g-oligo(epsilon-caprolactone) polymeric micelles: microwave-assisted synthesis and physicochemical and cytocompatibility characterization

With the aim to produce mucoadhesive polymeric micelles for drug administration by mucosal routes, chitosan-g-oligo(epsilon-caprolactone) copolymers were synthesized by the microwave-assisted ring-opening polymerization of epsilon-caprolactone using chitosan as the macroinitiator and methanesulfonic acid as the solvent, catalyst and protecting group of the amine moieties. The reaction was conducted under very mild conditions and was completed within 10 min with a monomer conversion above 90%. The grafting of oligo(epsilon-caprolactone) blocks to the free hydroxyl groups of chitosan was confirmed by ATR/FT-IR, 1H- and 13C-NMR, WAXD and thermal analysis (TGA/DSC). The molecular weight of the synthetic hybrid copolymers was determined by GPC and MALDI-ToF mass spectrometry. Polymeric micelles obtained by the solvent diffusion/evaporation method showed a spherical shape (TEM and AFM) with sizes between 111 and 154 nm and highly positive zeta potential (>+50 mV) (DLS). In addition, they displayed good cell compatibility in the human lung adenocarcinoma epithelial line, A549, and were readily up-taken by the cervical cancer cell line, HeLa. Results from the encapsulation of the antituberculosis drug, rifampicin, showed that the micelles had better performance than other nanocarriers previously investigated (e.g., cyclodextrins). Moreover, the micelles conserved the mucoadhesiveness displayed by pristine chitosan and are expected to transiently open tight cell junctions and lead to more prolonged residence times in mucosal tissues and greater drug bioavailability.Fil: Glisoni, Romina Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Nanobiotecnología. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Nanobiotecnología; ArgentinaFil: Quintana Lazópulos, Silvina Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Molina, María. Freie Universität Berlin; AlemaniaFil: Calderon, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Freie Universität Berlin; AlemaniaFil: Moglioni, Albertina Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; ArgentinaFil: Sosnik, Alejandro Dario. Technion - Israel Institute of Technology; Israel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Development of Mucoadhesive Gel Microbicide to Target Mucosal HIV Reservoirs

The wide use of microbicide is mainly depends on its effectiveness, less frequent application, ready availability and most importantly cost. The aim of this work was to develop affordable microbicide mucoadhesive gel formulation of synthetic anti HIV drug, stavudine and to characterise it in terms of its physical properties, mucoadhesiveness and spreadability. The purpose of the present study was also to compare different dissolution media used for in vitro release of vaginal dosage form. The gels were tested for antimicrobial, spermicidal and anti-HIV activity. Gels prepared using Carbopols and Polycarbophil were transparent and homogenous and had excellent mucoadhesion index - and showed fast drug release profile. Gels showed very good antimicrobial action against pathological microorganism

The parallel lives of polysaccharides in food and pharmaceutical formulations

The present opinion article discusses how polysaccharide structures can be used in both food and pharmaceutical formulations. We distinguish two regions depending on moisture content where polysaccharides form structures with distinct functional properties. Some trends in key areas of active research are assessed and in particular edible films, encapsulation, polycrystalline polysaccharides, protein-polysaccharide coacervation and fluid gels. We unveil that the physicochemical principles that are shared across the food and pharmaceutical disciplines provide a great opportunity for cross-disciplinary collaboration. We finally argue that such co-operation will help tackling polysaccharide functionality issues that are encountered in both areas

Assessing mucoadhesion in polymer gels : The effect of method type and instrument variables

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).The process of mucoadhesion has been widely studied using a wide variety of methods, which are influenced by instrumental variables and experiment design, making the comparison between the results of different studies difficult. The aim of this work was to standardize the conditions of the detachment test and the rheological methods of mucoadhesion assessment for semisolids, and introduce a texture profile analysis (TPA) method. A factorial design was developed to suggest standard conditions for performing the detachment force method. To evaluate the method, binary polymeric systems were prepared containing poloxamer 407 and Carbopol 971P®, Carbopol 974P®, or Noveon® Polycarbophil. The mucoadhesion of systems was evaluated, and the reproducibility of these measurements investigated. This detachment force method was demonstrated to be reproduceable, and gave different adhesion when mucin disk or ex vivo oral mucosa was used. The factorial design demonstrated that all evaluated parameters had an effect on measurements of mucoadhesive force, but the same was not observed for the work of adhesion. It was suggested that the work of adhesion is a more appropriate metric for evaluating mucoadhesion. Oscillatory rheology was more capable of investigating adhesive interactions than flow rheology. TPA method was demonstrated to be reproducible and can evaluate the adhesiveness interaction parameter. This investigation demonstrates the need for standardized methods to evaluate mucoadhesion and makes suggestions for a standard study design.Peer reviewedFinal Published versio

A mucosa-mimetic material for the mucoadhesion testing of thermogelling semi-solids

Mucosa-mimetic materials are synthetic substrates which aim to replace animal tissue in mucoadhesion experiments. One potential mucosa-mimetic material is a hydrogel comprised of N-acryloyl-d-glucosamine and 2-hydroxyethylmethacrylate, which has been investigated as a surrogate for animal mucosae in the mucoadhesion testing of tablets and solution formulations. This study aims to investigate the efficacy of this mucosa-mimetic material in the testing of thermogelling semi-solid formulations, which transition from solution to gel upon warming. Two methods for assessing mucoadhesion have been used; tensile testing and a flow-through system, which allow for investigation under dramatically different conditions. It was found that the mucosa-mimetic material was a good surrogate for buccal mucosa using both testing methods. This material may be used to replace animal tissue in these experiments, potentially reducing the number of laboratory animals used in studies of this type