Mucoadhesive Systems Research Articles

Therapeutic Effectiveness in the Treatment of Experimental Bacterial Keratitis with Ion-activated Mucoadhesive Hydrogel

Purpose: To investigate the therapeutic effectiveness of ion-activated mucoadhesive hydrogel system in the treatment of experimental bacterial keratitis.Materials and Methods: Mucoadhesive systems were prepared using gellan or sodium alginate alone and combined with sodium carboxymethylcellulose (NaCMC) to enhance the gel bioadhesion properties. The in vivo antimicrobial efficacy of selected mucoadhesive systems was studied in an experiment on bacterial keratitis in rabbit’s eyes and compared with that of the marketed conventional eyedrops.Results: Ocular tolerance was studied in the eye of albino rabbits and tested formulations were non-irritant with no sign of inflammation. Better improvement in experimental bacterial keratitis in rabbit eyes was observed in animals treated with mucoadhesive hydrogel formulation (GG5 and GS5) compared with marketed drug solution.Conclusion: The developed system is a viable alternative to conventional eyedrops of GTN due to its ability to enhance bioavailability through its longer precorneal residence time.

A curcumin-loaded liquid crystal precursor mucoadhesive system for the treatment of vaginal candidiasis.

Women often develop vaginal infections that are caused primarily by organisms of the genus Candida. The current treatments of vaginal candidiasis usually involve azole-based antifungals, though fungal resistance to these compounds has become prevalent. Therefore, much attention has been given to molecules with antifungal properties from natural sources, such as curcumin (CUR). However, CUR has poor solubility in aqueous solvents and poor oral bioavailability. This study attempted to overcome this problem by developing, characterizing, and evaluating the in vitro antifungal action of a CUR-loaded liquid crystal precursor mucoadhesive system (LCPM) for vaginal administration. A low-viscosity LCPM (F) consisting of 40% wt/wt polyoxpropylene-(5)-polyoxyethylene-(20)-cetyl alcohol, 50% wt/wt oleic acid, and 10% wt/wt chitosan dispersion at 0.5% with the addition of 16% poloxamer 407 was developed to take advantage of the lyotropic phase behavior of this formulation. Notably, F could transform into liquid crystal systems when diluted with artificial vaginal mucus at ratios of 1:3 and 1:1 (wt/wt), resulting in the formation of F30 and F100, respectively. Polarized light microscopy and rheological studies revealed that F behaved like an isotropic formulation, whereas F30 and F100 behaved like an anisotropic liquid crystalline system (LCS). Moreover, F30 and F100 presented higher mucoadhesion to porcine vaginal mucosa than F. The analysis of the in vitro activity against Candida albicans revealed that CUR-loaded F was more potent against standard and clinical strains compared with a CUR solution. Therefore, the vaginal administration of CUR-loaded LCPMs represents a promising platform for the treatment of vaginal candidiasis.

Optimization of curcumin loaded vaginal in-situ hydrogel by box-behnken statistical design for contraception

Sexually transmitted infections and unplanned pregnancies present a great risk to the reproductive health of women. Therefore, female-controlled vaginal products directed toward disease prevention and contraception is needed urgently. The purpose of this investigation was to develop poloxamer based thermo sensitive contraceptive vaginal in situ hydrogel of curcumin, a plant-derived diferuloylmethane compound. Different formulations using different ratio of poloxamer 407/188 and mucoadhesive polymer - HPMC K4M were prepared and optimized by box behnken experimental design (BBD). Formulations were optimized on the basis of gelation temperature (°C), gel strength (gm/cm2), Mucoadhesive strength (dyne/cm2), viscosity (Pa) and % drug release. Optimized formulation was subjected to In Vitro sperm immobilization study on 5 fertile human volunteers’ ejaculate sample. The quantitative effect of independent variables on dependent variables at different levels could be predicted by polynomial equations. From BBD, that batch containing 19.96% Poloxamer 407, 3.83% Poloxamer 188, 0.91% HPMC K4M was optimized. Total 100% Sperm immobilization was achieved within 15 min by optimized formulation for 3.5 ml of dose. Stability study of optimized batch shows no change in physical and chemical characteristics. Curcumin would be successfully formulated as thermo sensitive In Situ gelling mucoadhesive system for contraception.

Gut lipopolysaccharide binding by colistin decreases tissue injury during severe acute pancreatitis

Introduction: Gut derived lipopolysaccharide (LPS) is important factor in development of single and multiple organ failure during severe acute pancreatitis (SAP). Aims: To evaluate the effects of enteral administration of colistin (CS) on preventing LPS absorption from gut during SAP. Materials & methods: In 200 rats SAP was induced by L-arginine injection. Enteral administration of 2 mg/kg of CS every 6 h performed in CS high dose (CHD) group (n 1⁄4 10), 1 mg/kg every 12 h in CS low dose (CLD) group (n1⁄4 10), 1 mg/kg included in chitosan nanoparticles every 12 h in CS nanoparticles (CNP) group (n 1⁄4 10). Levels of LPS, sCD14, TNFa, morphological changes in pancreas, other internal organs and intestinal microbiota have been studied during 7 days. Results: CS administration caused reduction of LPS levels in faeces for 100-1000 times in all treated groups, but in mucus such events appeared only in CNP group. LPS concentrations in portal and system blood were similar to sham control level in CNP and elevated 2 and 4-5 times in CHD and CLD animals. Administration of CS reduced amounts of sCD14 and TNFa in all treatment cases, but only in CNP group there levels were closed to sham animals. Tissue injuries were much lesser in case of CNP group. Conclusion: Selective binding of gut-derived LPS during SAP by enteral administration of CS effectively decreases tissue injury in case it is incorporated to mucoadhesive nanoparticle delivery system or applied in high dose regimen. Abstracts / Pancreatolog S2

An overview of recent patents on composition of mucoadhesive drug delivery systems.

Mucoadhesion began to be applied to therapeutic systems with the aim of the incorporation of bioadhesive molecules into pharmaceutical dosage forms intended to keep in close contact with the tissue, releasing the drug near the action site, thereby increasing its bioavailability and promoting local or systemic effects. Different mucoadhesive materials and dosage forms have been studied, since the properties of mucoadhesion largely depend on the features of the material used in its preparation. This mini-review focuses on mucoadhesive therapeutic systems, the main mucosal routes of administration, and materials used to prepare the systems over the last five years. Patents and applications were reviewed, categorized and the materials were described together with the proposed systems.

Biophysical analysis of the molecular interactions between polysaccharides and mucin.

Mucoadhesive materials adhere persistently to mucosal surfaces. A mucoadhesive delivery system could therefore facilitate the controlled release of drugs and optimize their bioavailability in mucosal tissues. Polysaccharides are the most versatile class of natural polymers for transmucosal drug delivery. We used microviscosimetry to explore the mucoadhesion of a library of polysaccharide families with diverse structural characteristics as a first step toward the rational design of mucoadhesive polysaccharide-based nanoformulations. Here we show that the magnitude of deviation between the viscosity of mixed polysaccharide-mucin solutions and the corresponding individual stock solutions can indicate underlying molecular interactions. We found that nonlinear monotonic curves predicted a correlation between the magnitude of interaction and the ability of polysaccharide coils to contract in the presence of salt (i.e., chain flexibility). Charge-neutral polysaccharides such as dextran and Streptococcus thermophilus exopolysaccharide did not interact with mucin. Synchrotron small-angle X-ray scattering (SAXS) data supported the previously described structural features of mucin. Furthermore, high-q scattering data (i.e., sensitive to smaller scales) revealed that when mucin is in dilute solution (presumably in an extended conformation) in the presence of low-Mw alginate, its structure resembles that observed at higher concentrations in the absence of alginate. This effect was less pronounced in the case of high-Mw alginate, but the latter influenced the bulk properties of mucin-alginate mixtures (e.g., hydrodynamic radius and relative viscosity) more prominently than its low-Mw counterpart.

Layered nanoemulsions as mucoadhesive buccal systems for controlled delivery of oral cancer therapeutics.

Oral cavity and oropharyngeal cancers are considered the eighth most common cancer worldwide, with relatively poor prognosis (62% of patients surviving 5 years, after diagnosis). The aim of this study was to develop a proof-of-concept mucoadhesive lozenge/buccal tablet, as a potential platform for direct sustained delivery of therapeutic antimitotic nanomedicines. Our system would serve as an adjuvant therapy for oral cancer patients undergoing full-scale diagnostic and operative treatment plans. We utilized lipid-based nanocarriers, namely nanoemulsions (NEs), containing mixed-polyethoxylated emulsifiers and a tocopheryl moiety–enriched oil phase. Prototype NEs, loaded with the proapoptotic lipophilic drug genistein (Gen), were further processed into buccal tablet formulations. The chitosan polyelectrolyte solution overcoat rendered NE droplets cationic, by acting as a mucoadhesive interfacial NE layer. With approximate size of 110 nm, the positively charged chitosan-layered NE (+25 mV) vs negatively charged chitosan-free/primary aqueous NE (−28 mV) exhibited a controlled-release profile and effective mucoadhesion for liquid oral spray prototypes. When punch-pressed, porous NE-based buccal tablets were physically evaluated for hardness, friability, and swelling in addition to ex vivo tissue mucoadhesion force and retention time measurements. Chitosan-containing NE tablets were found equivalent to primary NE and placebo tablets in compression tests, yet significantly superior in all ex vivo adhesion and in vitro release assays (P≤0.05). Following biocompatibility screening of prototype chitosan-layered NEs, substantial anticancer activity of selected cationic Gen-loaded NE formulations, against two oropahryngeal carcinomas, was observed. The data strongly indicate the potential of such nanomucoadhesive systems as maintenance therapy for oral cancer patients awaiting surgical removal, or postresection of identified cancerous lesions.

Effects of epidermal growth factor-loaded mucoadhesive films on wounded oral tissue rafts

Current treatments for traumatic oral mucosal wounds include the gold standard of autologous tissue and alternative tissue-engineered grafts. While use of autografts has disadvantages of minimal availability of oral keratinized tissue, second surgery, and donor site discomfort, tissue-engineered grafts are limited by their unavailability as off-the-shelf products owing to their fabrication time of 4–8 weeks. Hence, the current work aimed to develop a potentially cost-effective, readily available device capable of enhancing native mucosal regeneration. Considering the key role of epidermal growth factor (EGF) in promoting mucosal wound regeneration and the advantages of mucoadhesive delivery systems, mucoadhesive films composed of polyvinylpyrrolidone and carboxymethylcellulose were developed to provide sustained release of EGF for a minimum of 6 h. Bioactivity of released EGF supernatants was then confirmed by its ability to promote proliferation of BALB/3T3 fibroblasts. Efficacy of the developed system was then investigated in vitro using buccal tissues (ORL 300-FT) as a potential replacement for small animal studies. Although the mucoadhesive films achieved their desired role of delivering bioactive EGF in a sustained manner, treatment with EGF, irrespective of its release from the films or solubilized in medium, caused a hyperparakeratotic response from in vitro tissues with distinguishable histological features including thickening of the spinous layer, intra- and intercellular edema, and pyknotic nuclei. These significant morphological changes were associated with no improvements in wound closure. These observations raise questions about the potential of using in vitro tissues as a wound healing model and substitute for small animal studies. The mucoadhesive delivery system developed, however, with its potential for sustained release of bioactive growth factors and small molecules, may be loaded with other desired compounds, with or without EGF, to accelerate the process of wound healing.

Development of amino acid substituted gemini surfactant-based mucoadhesive gene delivery systems for potential use as noninvasive vaginal genetic vaccination.

Recently, we synthesized amino acid- and peptide-substituted gemini surfactants, 'biolipids' that exhibited high transfection efficiency in vitro. In this study, we developed these plasmid DNA and gemini surfactant lipid particles for noninvasive administration in vaginal cavity. Novel formulations of these gene delivery systems were prepared with poloxamer 407 to induce in situ gelling of the formulation and diethylene glycol monoethyl ether to improve their penetration across mucosal tissue. Poloxamer at 16% w/v concentration in diethylene glycol monoethyl ether aqueous solution produced dispersions that gelled near body temperature and had a high yield value, preventing leakage of the formulation from the vaginal cavity. Intravaginal administration in rabbits showed that the glycyl-lysine-substituted gemini surfactant led to a higher gene expression compared with the parent unsubstituted gemini surfactant. This provides a proof-of-concept that amino acid substituted gemini surfactants can be used as noninvasive mucosal (vaginal) gene delivery systems to treat diseases associated with mucosal epithelia.

Design and Evaluation of Mucoadhesive Buccal Patches of Venlafaxine

Bioadhesive buccal delivery system is one of substitute to the oral route of drug administration; particularly drugs that are undergoing first pass effect. The rationale of this study was to develop a mucoadhesive buccal patch system containing drug venlafaxine with different ratios of polymeric systems like hydroxypropyl methyl cellulose E15, hydroxypropyl cellulose, methyl cellulose and sodium carboxymethyl cellulose by the solvent casting technique using propylene glycol as plasticizer. The physicochemical compatibility of the drug and the polymers were studied by FTIR and studies suggested absence of any incompatibility. Formulated buccal films were physically evaluated for thickness, weight variation, drug content, folding endurance, surface pH, swelling index, bioadhesive strength, in vitro residence time and in vitro drug release. All prepared Original Research Article Asif et al.; BJPR, 6(2): 96-106, 2015; Article no.BJPR.2015.053 97 formulations indicated good physical stability. Ex vivo permeation studies of optimized formulation was performed by using Franz diffusion cells. The release profile of venlafaxine followed zeroorder and first-order kinetics in different formulations. However, the release of the drug from optimized formulation A12 (R 2 = 0.9913 for Higuchi) was governed by diffusion mechanism and showed highest bioadhesive strength and in vitro residence time.

Hydrodynamically Balanced Gastro-Retentive Site Specific Drug Delivery System: An Innovative Approach

Conventional oral dosage forms suffer with many disadvantages. To avoid such limitations controlled release dosage forms are preferred. When these controlled release dosage forms administered by oral route retained in the stomach and release the drug in a controlled fashion continuously in gastrointestinal tract [1]. Controlled release systems also suffer with some limitations such as short gastric retention time and unpredictable short gastric emptying time, which leads to incomplete drug release in the absorption zone results into reduced efficiency of the dose administered [2]. To achieve a desirable prolonged gastric residence time, it is essential to design a site-specific controlled oral dosage form. The prolonged gastric retention of a dosage form increases the total duration of drug release, improves bioavailability, minimizes the drug loss and enhances solubility of poorly soluble drugs in gastric environment [3]. Furthermore, prolonged gastric retention time in the stomach also leads to effective local action in the upper part of the small intestine especially in the treatment of peptic ulcer. Hydrodynamically balanced gastric retentive drug delivery is an innovative approach play important role in prolonging gastric residence time by targeting site specific drug release in the upper intestine for local as well as systemic effect. Over the last few decades different kinds of gastroretentive drug delivery systems being developed. Main among these are: high density (sinking) systems that are designed to sink into the gastric fluid and settle at the bottom of stomach [4], low density (floating) systems that are designed to float on the gastric fluid causing buoyancy [5-7], mucoadhesive systems that are designed to adhere to stomach mucosa [8], unfoldable, extendable, or swellable systems that are designed to limit the emptying of the dosage forms through the pyloric sphincter of stomach [9], superporous hydrogel systems [10] and magnetic systems [11]. The current editorial focused mainly on concise information about hydrodynamically balanced site specific gastroretentive approach for orally administered controlled release dosage forms.

Poly(acrylic acid)/polyethylene glycol hygrogel prepared by using gamma-ray irradiation for mucosa adhesion

A buccal delivery system provides a much milder environment for drug delivery compared to an oral delivery which presents a hostile environment for drugs, especially proteins and polypeptides, owing to acid hydrolysis. Local delivery in an oral cavity has particular applications in the treatment of toothaches, periodontal disease, and bacterial infections. Poly(acrylic acid) (PAA)-based hydrogels prepared using a chemical initiator have been attempted for a mucoadhesive system owing to their flexibility and excellent bioadhesion. In this experiment, PAA and polyethylene glycol (PEG) were selected to prepare using a radiation process a bioadhesive hydrogel for adhesion to mucosal surfaces. PAA and PEG were dissolved in purified water to prepare a homogeneous PAA/PEG solution, and the solution was then irradiated using an electron beam at dose up to 70 kGy to make the hydrogels. Their physical properties, such as gel percent, swelling percent, and adhesive strength to mucosal surfaces, were investigated. In this experiment, various amounts of PEG were incorporated into the PAA to enhance the mucoadhesive property of the hydrogels. The effect of the molecular weight of PEG on the mucoadhesion was also examined.

Oral Strip Drug Delivery System

Oral Strip Technology (OST) is gaining much attention. The advantages of OST are the administration to pediatric and geriatric patient population where the difficulty of swallowing larger oral dosage forms is eliminated. This technology has been used for local action, rapid release products and for mucoadhesive systems that are retained for longer period in the oral cavity to release drug in controlled fashion. OST offers an alternate platform for molecules that undergo first pass metabolism and for delivery of peptides. An ideal OST should have the following properties: high stability, transportability, ease of handling and administration, no special packaging material and/or processing requirements, no water necessary for application and a pleasant taste. These entire requirements are fulfilled by the oral films. The OST is a good tool for product life cycle management for increasing the patent life of existing molecules or products. Compared to some of the complicated and expensive process (like lyophilization) used to manufacture ODTs (Orally Disintegrating Tablets), the OST is relatively easy to fabricate, thus reducing the overall cost of the therapy. One of the reasons is that the buccal mucosa is less permeable and is thus not able to elicit a rapid onset of absorption and hence better suited for formulations that are intended for sustained release action. Further, the buccal mucosa being relatively immobile mucosa and readily accessible, it makes it more advantageous for retentive systems used for oral Tran's mucosal drug delivery. The primary disadvantage associated with buccal delivery route is the low flux that in turn results in low drug bioavailability. To overcome this hurdle, various buccal penetration enhancers have been studied which improve the absorption pattern of the molecules. The article shows OST encompassing materials used in OST, method of Preparation, Evaluation, Applications, Commercial technologies and future Business prospects of this technology. The oral film is manufacture using solvent casting method, rolling method, extrusion method and solid dispersion method.

Mucoadhesive System Formed by Liquid Crystals for Buccal Administration of Poly(Hexamethylene Biguanide) Hydrochloride

Antimicrobial approaches are valuable in controlling the development of buccal diseases, but some antibacterial agents have a short duration of activity. Therefore, the development of prolonged delivery systems would be advantageous. Liquid crystalline systems comprising monoolein (GMO)/water have been considered to be a potential vehicle to deliver drugs to the buccal mucosa because of the phase properties that allow for controlled drug release as well as its mucoadhesive properties. Therefore, the aim of this study was to develop a GMO/water system for the slow release of poly(hexamethylene biguanide) hydrochloride (PHMB) on the buccal mucosa and test the properties of this system with regard to swelling, release profile, antimicrobial activity, and strength of mucoadhesion, with the overall goal of treating buccal infections. The tested systems were capable of modulating drug release, which is controlled by diffusion of the drug throughout the system. Furthermore, PHMB appeared to improve the mucoadhesive properties of the system and may synergistically act with the drug to promote antimicrobial activity against S. mutas and C. albicans, indicating that liquid crystals may be suitable for the administration of PHMB on the buccal mucosa. Therefore, this system could be proposed as a novel system for mucoadhesive drug delivery.

DESIGN AND DEVELOPMENT OF NOVEL MUCOADHESIVE GASTRORETENTIVE FORMULATION OF GLIPIZIDE

The aim of the present study was to develop and characterize a gastroretentive formulati on for controlled drug release and to develop innovative gastro retentive formulation based on mucoadhesive patch systems using the solvent casti ng technique. Glipizide, an anti diabetic agent was used as model drug for formulating films. Mucoadhesive film was formulated using chitosan and HPMC K 4 M. PEG 400 was added as plasticizer in film preparation. 3 2 full f actorial design was used to formulate the novel gastroretentive formulation. Amount of HPMC K 4 M(X 1 ) and amount of chitosan (X 2 ) was selected as independent variable while swelling index, folding endurance, mucoadhesion force and Q 8 (% drug release after 8 h ) was selected as dependent variables. The film with zigzag folding in the capsule was shown to unfold and swell under acidic condi tions and provide controlled release of drug upto12 h in acidic medium. According to 3 2 full factorial design films , 9 batch es were prepared and evaluated for surface pH, folding endurance, mucoadhesion force, drug content, in - vitro drug release etc. Surface pH of F1 - F9 was in between 6.32 to 6.98. Thickness and % drug content for batch F1 - F9 was found to be in between 0.236 m m to 0.289 mm and 95.42 % to 99.32 %, respectively. In - vitro drug release study of F1 - F9 showed utmost 95 % drug release after 11 h. The results indicate that the dosage form is gastroretentive and can provide controlled release of drugs with narrow therap eutic window. Glipizide/ HPMCK 4 M / Chitosan (40:150:150) F8 was found to be optimized composition of mucoadhesive films that showed good swelling index, folding endurance, sur face pH, mucoadhesion force, Q8 and % drug content.

Preparation and characterization of mucoadhesive nanoparticles of poly (methyl vinyl ether-co-maleic anhydride) containing glycyrrhizic acid intended for vaginal administration

Traditional vaginal preparations reside in the vaginal cavity for relatively a short period of time, requiring multiple doses in order to attain the desired therapeutic effect. Therefore, mucoadhesive systems appear to be appropriate to prolong the residence time in the vaginal cavity. In the current study, mucoadhesive nanoparticles based on poly(methyl vinyl ether-co-maleic anhydride) (PVM/MA) intended for vaginal delivery of glycyrrhizic acid (GA) (a drug with well-known antiviral properties) were prepared and characterized. Nanoparticles were generated by a solvent displacement method. Incorporation of GA was performed during nanoprecipitation, followed by adsorption of drug once nanoparticles were formed. The prepared nanoparticles were characterized in terms of size, Z-potential, morphology, drug loading, interaction of GA with PVM/MA (by differential scanning calorimetry) and the in vitro interaction of nanoparticles with pig mucin (at two pH values, 3.6 and 5; with and without GA adsorbed). The preparation method led to nanoparticles of a mean diameter of 198.5 ± 24.3 nm, zeta potential of −44.8 ± 2.8 mV and drug loading of 15.07 ± 0.86 µg/mg polymer. The highest mucin interaction resulted at pH 3.6 for nanoparticles without GA adsorbed. The data obtained suggest the promise of using mucoadhesive nanoparticles of PVM/MA for intravaginal delivery of GA.

Genipin-crosslinked catechol-chitosan mucoadhesive hydrogels for buccal drug delivery

Drug administration via buccal mucosa is an attractive drug delivery strategy due to good patient compliance, prolonged localized drug effect, and avoidance of gastrointestinal drug metabolism and first-pass elimination. Buccal drug delivery systems need to maintain an intimate contact with the mucosa lining in the wet conditions of the oral cavity for long enough to allow drug release and absorption. For decades, mucoadhesive polymers such as chitosan (CS) and its derivatives have been explored to achieve this. In this study, inspired by the excellent wet adhesion of marine mussel adhesive protein, we developed a buccal drug delivery system using a novel catechol-functionalized CS (Cat-CS) hydrogel. We covalently bonded catechol functional groups to the backbone of CS, and crosslinked the polymer with a non-toxic crosslinker genipin (GP). We achieved two degrees of catechol conjugation (9% and 19%), forming Cat9-CS/GP and Cat19-CS/GP hydrogels, respectively. We confirmed covalent bond formation during the catechol functionalization and GP crosslinking during the gel formation. The gelation time and the mechanical properties of Cat-CS hydrogels are similar to those of CS only hydrogels. Catechol groups significantly enhanced mucoadhesion in vitro (7 out of the 10 Cat19-CS hydrogels were still in contact with porcine mucosal membrane after 6 h, whereas all of the CS hydrogels lost contact after 1.5 h). The new hydrogel systems sustained the release of lidocaine for about 3 h. In-vivo, we compared buccal patches made of Cat19-CS/GP and CS/GP adhered to rabbit buccal mucosa. We were able to detect lidocaine in the rabbit's serum at concentration about 1 ng/ml only from the Cat19-CS patch, most likely due to the intimate contact provided by mucoadhesive Cat19-CS/GP systems. No inflammation was observed on the buccal tissue in contact with any of the patches tested. These results show that the proposed catechol-modified CS hydrogel is a promising mucoadhesive and biocompatible hydrogel system for buccal drug delivery.

Development of alginate microspheres as nystatin carriers for oral mucosa drug delivery

To develop more effective antifungal mucoadhesive systems for the treatment of oral candidiasis, three types of microspheres, alginate (AM1), chitosan coated (CCM) and hydrogel (AM2) containing nystatin (Nys) were successfully elaborated by emulsification/internal gelation method. Physicochemical properties of microspheres resulted in 85–135μm mean sizes, spherical shaped with narrow distribution. Optimal encapsulation efficiency and negative zeta potentials were observed. AM2 showed a consistent decrease in viscosity with increasing shear rate (Herschel–Bulkley). Optimal mucoadhesive properties and swelling behaviour where evidenced. Nys release from AM1 and CCM followed a concentration gradient pattern, contrary AM2 followed a complex release mechanism. All systems exhibited a marked fungicidal activity against Candida albicans strains. In vivo studies demonstrated that Nys was not found in systemic circulation assuring the safety of the treatment. Nys amounts retained in the mucosa were more than enough to ensure an effective fungicidal action without tissue damage. Based on the obtained results, AM2 could be proposed as the vehicle with the best properties for the buccal vehiculization of Nys.

Editorial (Thematic Issue: Oral Delivery of Biotechnology based Drugs: Dream or Reality?)

Biotechnology has provided a wide array of therapeutic agents such as peptide, protein, vaccine and gene products that are currently mainly administered by means of injections. Therapeutic agents produced by biotechnological processes such as recombinant DNA technology, fermentation, tissue and cell culture technology as well as genetic engineering are usually large, hydrophilic molecules facing delivery challenges, for example, these drugs are susceptible to degradation and are generally poorly membrane permeable. Since successful delivery of any drug is a pre-requisite to achieve the therapeutic goal, novel strategies have emerged in the late 20th century to overcome challenges associated with the oral route of drug administration. These strategies include, but are not restricted to micro- and nanotechnology including self-emulsifying lipid based formulations, dendrimers and devices, permeability enhancing technology, targeting of active transporters and membrane receptors, use of cell penetrating peptides, chemical modifications of peptides such as inclusion complex formation and peptide conjugates, site-specific delivery systems, muco-adhesive systems and polymeric hydrogels. Despite the initial excitement regarding the potential of these technologies to provide effective oral delivery, few have advanced from the pre-clinical stage into clinical trials and very few, if any, resulted so far in registered medicinal products. Moreover, most literature provides information on effectiveness and mechanisms based on in vitro investigations without revealing the viability of these technologies in clinical practice. Although this topic of oral peptide delivery has gone through different phases in terms of attracting attention from the scientific community, it remains a timely research subject. The therapeutic benefits to patients and potential economic benefits to the producer serve as the driving forces behind finding an effective oral delivery system for biotechnology derived drugs. This special issue aims at assessing some of the latest developments in the field of oral delivery of biotechnological therapeutic agents. The reader will not only gain an understanding of the challenges associated with oral delivery of protein and peptide based drugs, but certain strategies that emerged to overcome these drawbacks are also discussed. From the discussions it is clear that scientific research has contributed to a deeper understanding of older drug delivery strategies, while new discoveries keep the vision of producing an effective oral peptide drug delivery system alive.

Development of Mucoadhesive Nanoparticulate System of Ebastine for Nasal Drug Delivery

Purpose: To prepare and evaluate mucoadhesive nanoparticulate system of ebastine for nasal drug delivery.Methods: The nanoparticles were prepared by ionic gelation method using drug-chitosan weight ratios 1:1, 1:2 and 1:3, and incorporating 0.5 or 0.7 % w/v sodium tripolyphosphate (STPP) and poloxamer 407. The mucoadhesive nanoparticles were characterized by scanning electron microscope (SEM), transmission electron microscope (TEM), differential scanning colorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) and evaluated for drug loading, entrapment efficiency, in vitro mucoadhesion, in vitro drug release and ex-vivo permeation.Results: FTIR and DSC studies indicate that no chemical interaction occurred between the drug and polymer. Nanoparticle size ranged from 169 to 500 nm. Drug loading and entrapment efficiency increased with increase in chitosan concentration and decreased with increase in poloxamer 407 concentration. The highest drug loading obtained for the nanoparticles was 19.5 %. With increase in polymer (chitosan) concentration (1:1 to 1:3), production yield was unchanged (73.2 to 74.4 % (F6)). Mucoadhesion increased with increase in the concentration of chitosan. In vitro drug release from all the formulations was biphasic, being characterized by a slight ‘burst’ followed by slow release. At the end of 8 h F6 (1:3) showed drug release of only 86.9 %, indicating sustained release. Ex-vivo permeation of pure ebastine was more rapid than from F6, thus indicating the capability of chitosan to control drug permeation rate through sheep nasal mucosa.Conclusion: The results indicate that a mucoadhesive nanoparticulate system can be used effectively for the nasal delivery of the antihistamine, ebastine.Keywords: Chitosan, Ebastine, Mucoadhesive, Nanoparticles, Ionotropic gelation, Permeation, Drug release, Poloxamer