Mucoadhesive Drug Delivery System Research Articles

Less Reactive Thiol Ligands: Key towards Highly Mucoadhesive Drug Delivery Systems.

As less reactive s-protected thiomers can likely interpenetrate the mucus gel layer to a higher extent before getting immobilized via disulfide bond formation with mucins, it was the aim of this study to develop a novel type of s-protected thiomer based on the less reactive substructure cysteine-N-acetyl cysteine (Cys-NAC) in order to obtain improved mucoadhesive properties. For this purpose, two types of s-protected thiomers, polyacrylic acid-cysteine-mercaptonicotinic acid (PAA-Cys-MNA) and polyacrylic acid-cysteine-N-acetyl cysteine (PAA-Cys-NAC), were synthesized and characterized by Fourier-transform infrared spectroscopy (FT-IR) and the quantification of attached disulfide ligands. The viscosity of both products was measured in the presence of NAC and mucus. Both thiomers were also evaluated regarding swelling behavior, tensile studies and retention time on the porcine intestinal mucosa. The FT-IR spectra confirmed the successful attachment of Cys-MNA and Cys-NAC ligands to PAA. The number of attached sulfhydryl groups was in the range of 660–683 µmol/g. The viscosity of both s-protected thiomers increased due to the addition of increasing amounts of NAC. The viscosity of the mucus increased in the presence of 1% PAA-Cys-MNA and PAA-Cys-NAC 5.6- and 10.9-fold, respectively, in comparison to only 1% PAA. Both s-protected thiomers showed higher water uptake than unmodified PAA. The maximum detachment force (MDF) and the total work of adhesion (TWA) increased in the case of PAA-Cys-MNA up to 1.4- and 1.6-fold and up to 2.4- and 2.8-fold in the case of PAA-Cys-NAC. The retention of PAA, PAA-Cys-MNA, and PAA-Cys-NAC on porcine intestinal mucosa was 25%, 49%, and 76% within 3 h, respectively. The results of this study provide evidence that less reactive s-protected thiomers exhibit higher mucoadhesive properties than highly reactive s-protected thiomers.

Advances in the Design of pH-Sensitive Cubosome Liquid Crystalline Nanocarriers for Drug Delivery Applications.

Nanostructure bicontinuous cubic phase self-assembled materials are receiving expanding applications as biocompatible delivery systems in various therapeutic fields. The functionalization of cubosome, spongosome, hexosome and liposome nanocarriers by pH-sensitive lipids and/or pH-sensitive polymer shells offers new opportunities for oral and topical drug delivery towards a new generation of cancer therapies. The electrochemical behavior of drug compounds may favor pH-triggered drug release as well. Here, we highlight recent investigations, which explore the phase behavior of mixed nonlamellar lipid/fatty acid or phospholipid systems for the design of pH-responsive and mucoadhesive drug delivery systems with sustained-release properties. X-ray diffraction and small-angle X-ray scattering (SAXS) techniques are widely used in the development of innovative delivery assemblies through detailed structural analyses of multiple amphiphilic compositions from the lipid/co-lipid/water phase diagrams. pH-responsive nanoscale materials and nanoparticles are required for challenging therapeutic applications such as oral delivery of therapeutic proteins and peptides as well as of poorly water-soluble substances. Perspective nanomedicine developments with smart cubosome nanocarriers may exploit compositions elaborated to overcome the intestinal obstacles, dual-drug loaded pH-sensitive liquid crystalline architectures aiming at enhanced therapeutic efficacy, as well as composite (lipid/polyelectrolyte) types of mucoadhesive controlled release colloidal cubosomal formulations for the improvement of the drugs’ bioavailability.

Long-acting mucoadhesive thermogels for improving topical treatments of dry eye disease.

Dry eye disease (DED) is the most common ocular disorder that causes persistent discomfort and blurry vision in patients. Despite pharmacotherapy strategies, the current topical administration of eye drops remains a great challenge owing to their low bioavailability and short residence time. Herein, we demonstrate an effective topical treatment of DED via rational design of a long-acting and mucoadhesive drug delivery system. Specifically, the drug carrier is a chemically ternary material system consisting of gelatin that serves as an enzyme-mediated degradable matrix, poly(N-isopropylacrylamide) as a thermo-responsive regulator, and lectin Helix pomatia agglutinin as a mucus-binding component. The long-acting drug release performance is exploited via initiator effects during the synthesis of the thermo-responsive polymer, while the mucoadhesive feature is inherited from the mucus-binding material. In a rabbit model of DED, a pharmacotherapy based on one-time topical administration of epigallocatechin gallate-loaded carrier onto the cul-de-sac could effectively repair the defective corneal epithelium via mitigating cellular inflammation, oxidative stress, and cell apoptosis for a sustained period over 14days. These findings on the initiator and synergy effects in the development of the advanced ophthalmic formulation show great promise for efficient management of complex ocular diseases by a simple topical administration route.

Development and Evaluation of Mucoadhesive Tablets of Cinnarizine Using Carboxymethylated Guar Gum by Compression Coating Technique

The e study was designed to perform carboxymethylation of guar gum and to develop mucoadhesive tablets of cinnarizine by compression coating technology. Carboxymethyl guar gum was synthesized and characterized by FTIR, SEM, XRD and DSC techniques. Inner core tablets of cinnarizine were compression coated with guar gum and carboxymethylated guar gum. The formulated mucoadhesive tablets were evaluated for various tablet parametric tests viz. hardness, friability, content uniformity, thickness. Ex vivo mucoadhesion strength and in vitro drug release studies were also conducted. Appearance of new FTIR peaks, surface morphology analysis by SEM, reduction in crystallinity by XRD and appearance of the endothermic peak in DSC thermogram point out towards successful carboxymethylation of guar gum. Mucoadhesive strength of F1CGG to F4CGG batches of mucoadhesive tablets prepared with carboxymethyl guar gum found higher than F1GG to F4GG batches of tablets prepared with guar gum. Carboxymethyl guar gum exhibited sustained release effect on in vitro release cinnarizine from compression coated mucoadhesive tablets. The study confirms that carboxymethylation of guar gum improves the mucoadhesive properties of pure guar gum. Also, the compression coating of carboxymethylated guar gum enhances the gastric retention time and sustained release of cinnarizine. Carboxymethyl guar gum can be used as mucoadhesive polymer for developing different mucoadhesive drug delivery systems.

Mucoadhesive Chitosan Delivery System with Chelidonii Herba Lyophilized Extract as a Promising Strategy for Vaginitis Treatment.

Chelidonium majus (also known as celandine) contains pharmacologically active compounds such as isoquinoline alkaloids (e.g., chelidonine, sanguinarine), flavonoids, saponins, carotenoids, and organic acids. Due to the presence of isoquinoline alkaloids, Chelidonii herba extracts are widely used as an antibacterial, antifungal, antiviral (including HSV-1 and HIV-1), and anti-inflammatory agent in the treatment of various diseases, while chitosan is a biocompatible and biodegradable carrier with valuable properties for mucoadhesive formulations preparation. Our work aimed to prepare mucoadhesive vaginal drug delivery systems composed of Chelidonii herba lyophilized extract and chitosan as an effective way to treat vaginitis. The pharmacological safety of usage of isoquinoline alkaloids, based on MTT test, were evaluated for the maximum doses 36.34 ± 0.29 µg/mL and 0.89 ± 1.16 µg/mL for chelidonine and sanguinarine, respectively. Dissolution rate profiles and permeability through artificial membranes for chelidonine and sanguinarine after their introduction into the chitosan system were studied. The low permeability for used save doses of isoquinoline alkaloids and results of microbiological studies allow confirmation that system Chelidonii herba lyophilized extract chitosan 80/500 1:1 (w/w) is a promising strategy for vaginal use. Ex vivo studies of mucoadhesive properties and evaluation of tableting features demonstrated that the formulation containing Chelidonii herba lyophilized extract (120.0 mg) with chitosan (80/500—100.0 mg) and polymer content (HPMC—100.0 mg, microcrystalline cellulose—50.0 mg, lactose monohydrate—30.0 mg and magnesium stearate—4.0 mg) is a vaginal dosage form with prolonging dissolution profile and high mucoadhesion properties (up to 4 h).

Synthesis and characterization of a pH responsive and mucoadhesive drug delivery system for the controlled release application of anti-cancerous drug

In this work a novel pH sensitive composite, polyacrylamide grafted succinyl chitosan intercalated bentonite (AAm-g-NB/SC) was prepared as a drug carrier system for the controlled delivery of paclitaxel. Characterization of the drug delivery system was carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), thermal analysis etc. The equilibrium swelling behaviour of the composite was studied and the result showed a maximum at pH 7.4. The in vitro drug release study of paclitaxel indicated that about 15.6% of drug release was found to be occurred at pH 1.2 within 16 h, whereas about 82.5% of drug release was occurred at the intestinal pH condition of 7.4. In vitro biocompatibility study was performed and the result showed good biocompatibility of the composite in the concentration range 6.25–100 µg/mL. The cytotoxicity assay was carried out in cancerous cell line of Human colorectal Adenocarcinoma. Mucous glycoprotein assay study showed that the drug delivery system having good apparent adhering property towards mucin. The investigation indicated that paclitaxel, an anticancer drug can be successfully entrapped in the AAm-g-NB/SC composite for the controlled and targeted delivery for colorectal cancer therapy.

Okra-Thioglycolic Acid Conjugate—Synthesis, Characterization, and Evaluation as a Mucoadhesive Polymer

The success of mucoadhesive drug delivery systems relies on the type of polymer used, which becomes adhesive naturally upon hydration. Intended polymers should be able to maintain prolonged contact with biological membranes, and to protect or cater the drug to a prolonged period. Most of the hydro polymers form weak non-covalent bonds, that hinder localization of dosage forms at specific sites resulting in therapeutic inefficiency. This can be overcome by the thiol functionalization of natural polymers. In the present study, natural okra gum (OG) was extracted, followed by thiolation (TOG) and evaluated for mucoadhesion property and its role in enhancing the efficacy of repaglinide as a model drug (short-acting Type II antidiabetic drug). The thiol functionalization of OG (TOG) was confirmed by a Fourier-transform infrared spectroscopy (FTIR) study that showed a polyhedral to a spherical shape that had a rougher surface. Differential scanning calorimetry (DSC) and X-Ray Diffraction (XRD) studies of TOG indicated a decline in endothermic transition temperature and high crystallinity, respectively, in comparison to OG. CSFR (Crushing Strength: Friability Ratio), weight and thickness variations of repaglinidetablets formulated using TOG were >80% and <2.5% respectively. The highest swelling index (107.89 ± 1.99%) and strong mucoadhesion due to high disulfide bonds were observed for repaglinide TOG tablets in comparison to RG OG tablets. In-vitro release studies indicated a controlled drug release from thiolated formulations proportional to the concentration of thiomers that have a good correlation with in-vivo studies. Pharmacokinetic studies indicated higher AUC (area under the curve), longer t1/2 with thiomers. and Level A IVIV (in vitro in vivo) correlation was established from the bioavailability and dissolution data. Consequently, all the obtained results suggest that thiomers based formulations can be promising drug delivery systems, even in targeting onerous mucosal surfaces like nasal, ocular or vaginal.

Formulation and evaluation of hyaluronic acid-based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer

The present study was intended to develop a papain grafted S-protected hyaluronic acid-lithocholic acid co-block (PAP-HA-ss-LCA) polymeric excipient as an amphiphilic muco permeating stabilizer for targeting breast cancer epithelial cells overexpressed with CD44 receptors. The mucopermeating, stabilizing and targeting capability of the PAP-HA-ss-LCA polymeric excipient was investigated by manufacturing tamoxifen (TMX) loaded self-nanoemulsifying drug delivery system (SNEDDS). TMX loaded PAP-HA-ss-LCA incorporated SNEDDS (TMX-PAP-HA-ss-LCA SNEDDS) were characterized for their surface chemistry, drug release, permeation enhancement, biocompatibility and antitumor activity. FTIR spectroscopic analysis showed successful synthesis of PAP-HA-ss-LCA polymer. X-ray diffraction (XRD) showed the amorphous form of TMX inside SNEDDS. The observed hydrodynamic diameter of TMX-PAP-HA-ss-LCA SNEDDS was 367.5 nm. Furthermore, Hyaluronic Acid-based Mucoadhesive Self Nanoemulsifying Drug Delivery System (SNEDDS) of TMX showed homogeneity in synthesis with low polydispersity and negative zeta potential due to stabilization with PAP-HA-ss-LCA polymer. The distinct spherical shape of the nanodroplets was evident by transmission electron microscopy (TEM). In vitro release kinetics indicated approximately >80% release within 48 h under sink conditions. Ex-vivo permeation study displayed 7.11-folds higher permeation of TMX by TMX-PAP-HA-ss-LCA in contrast to pure TMX. The biocompatibility study proved that SNEDDS formulation was safe and compatible against macrophages. In vitro cytotoxicity studies demonstrated that TMX-PAP-HA-ss-LCA SNEDDS could efficiently kill MCF-7 breast cancer cells as compared to the native TMX drug. Systemic toxicity studies proved the non-toxic nature of TMX-PAP-HA-ss-LCA in contrast to pure TMX. Based on these evidences, TMX-PAP-HA-ss-LCA SNEDDS formulation seems to be promising mucopermeating, augmented intracellular uptake with strong targeting potential for anti-proliferative activity.

Poly(amidoamine)-modified mesoporous silica nanoparticles as a mucoadhesive drug delivery system for potential bladder cancer therapy

Bladder cancer, with the highest recurrence rate in all malignancy, is a common urologic cancer that arises on the bladder mucosa. Currently, tumor resection followed by intravesical chemotherapy is the primary treatment of bladder cancer, which has limited effectiveness ascribe to short dwell-time of intravesical drugs in bladder. Therefore, there is a need to develop mucoadhesive and sustained drug delivery systems to increase drug residence time for intravesical chemotherapy. In this study, poly(amidoamine) (PAMAM) dendrimers were modified onto the surface of mesoporous silica nanoparticles (MSNPs) through a layer-by-layer grafting method. A series of PAMAM-modified MSNPs were prepared and compared for their mucoadhesive capabilities on pig bladder wall and controlled drug release properties. Results demonstrated an increase in the mucoadhesive capacity of PAMAM-modified MSNPs upon an increase in the number of PAMAM amino groups, and the maximum nanoparticle mucoadhesivity was observed after two-generation PAMAM were grafted on the surface of MSNPs. An antineoplastic, doxorubicin, was encapsulated in the mesopores of PAMAM-modified MSNPs, and the drug-loaded nanoparticles can provide a sustained drug release triggered by acidic pH. The present study demonstrates that the mucoadhesive and drug release properties of MSNPs can be controlled by the layer number of PAMAM dendrimers on the nanoparticle surface, holding significant potential for the development of mucoadhesive drug delivery systems for bladder cancer therapy.

Mucin-polysaccharide interactions: A rheological approach to evaluate the effect of pH on the mucoadhesive properties

The design of mucoadhesive drug delivery systems (DDS) based on polysaccharides at nanoscale or microscale is a relevant technological strategy for the mucosal delivery of several drugs. Findings about the potential mucoadhesive ability of these materials and the mechanisms that drive such interactions represents an important advance for the rational modulation of these properties, according to specific uses. The potential mucoadhesive abilities of gellan gum (GG) and retrograded starch (RS) were investigated at pH 1.2 and 6.8, which were considered biorrelevant for the gastrointestinal tract (GIT). The effects of these polysaccharides on the MUC rheology were also addressed. Rheological studies revealed high MUC-GG interactions at both pH values (1.2 and 6.8), expressing a high mucoadhesive ability, mainly in acidic media. MUC-GG interactions were driven, mainly, by hydrogen bonds. At an acidic pH, significant changes occurred in the MUC arrangements due to the strong MUC-GG interactions, as corroborated by scanning electron microscopy (SEM). The rheological behavior of MUC-RS indicated poor interactions between them and MUC arrangements were more preserved as evidenced by SEM. The results of this work indicated that the mixing of GG and RS can be a promising strategy to modulate mucoadhesiveness of DDS, according to specific therapeutic needs.

A systemic review on floating mucoadhesive drug delivery system and its present scenario

A systemic review on floating mucoadhesive drug delivery system and its present scenario

HPMC- and PLGA-Based Nanoparticles for the Mucoadhesive Delivery of Sitagliptin: Optimization and In Vivo Evaluation in Rats.

Mucoadhesive nanoparticles represent a potential drug delivery strategy to enhance the therapeutic efficacy in oral therapy. This study assessed the prospective of developing HPMC- and PLGA-based nanoparticles using a nanospray drier as a mucoadhesive extended release drug delivery system for sitagliptin and evaluated their potential in an animal model. Nanoparticles were prepared using a Buchi® B-90 nanospray drier. Optimization of particle size was performed using response surface methodology by examining the influence of spray-drying process variables (inlet temperature, feed flow, and polymer concentration) on the particle size. The prepared nanoparticles were characterized for various physicochemical characteristics (yield, drug content, morphology, particle size, thermal, and crystallographic properties) and assessed for drug release, stability, and mucoadhesive efficacy by ex vivo and in vivo studies in rats. A linear model was suggested by the design of the experiments to be the best fit for the generated design and values. The yield was 77 ± 4%, and the drug content was 90.5 ± 3.5%. Prepared nanoparticles showed an average particle size of 448.8 nm, with a narrow particle size distribution, and were wrinkled. Thermal and crystallographic characteristics showed that the drug present in the nanoparticles is in amorphous dispersion. Nanoparticles exhibited a biphasic drug release with an initial rapid release (24.9 ± 2.7% at 30 min) and a prolonged release (98.9 ± 1.8% up to 12 h). The ex vivo mucoadhesive studies confirmed the adherence of nanoparticles in stomach mucosa for a long period. Histopathological assessment showed that the formulation is safe for oral drug delivery. Nanoparticles showed a significantly higher (p < 0.05) amount of sitagliptin retention in the GIT (gastrointestinal tract) as compared to control. The data observed in this study indicate that the prepared mucoadhesive nanoparticles can be an effective alternative delivery system for the oral therapy of sitagliptin.

Antibacterial Activity of Mucoadhesive Gastroretentive Drug Delivery System of Alginate Beads Containing Turmeric Extract - PVP Solid Dispersion.

BACKGROUND:Turmeric extract is less effective because the main ingredient of curcumin has a low solubility. Therefore, it is necessary to convert turmeric extract into a solid dispersion form to increase the dissolution of curcumin.AIM:To determine the antibacterial activity of mucoadhesive gastroretentive drug delivery system of alginate beads containing solid dispersion of turmeric extract.METHODS:Turmeric powder was macerated with 96% ethanol for 8 days. The macerate was evaporated with a rotary evaporator at 50°C to obtain concentrated extract. Solid dispersion of turmeric extract was prepared by solvent method by using polyvinylpyrrolidone (PVP) K30 with a ratio of 1: 1 and 1: 2. The solid dispersion of turmeric extract was encapsulated with alginate gel by gelation method. The antibacterial of alginate beads containing solid dispersion of turmeric extract was tested by using hole agar plate diffusion method against Staphylococcus aureus and Escherichia coli as bacterial models.RESULTS:The size of alginate beads containing turmeric extract-PVP solid dispersion was about 1.3 mm. Antibacterial activity test against Staphylococcus aureus and Escherichia coli showed that alginate beads containing turmeric extract-PVP solid dispersion gave stronger antibacterial activity than those containing turmeric extract without solid dispersion. The antibacterial activity of alginate beads turmeric extract-PVP (1: 2) solid dispersion was stronger than those containing turmeric-extract (1: 1) solid dispersion.CONCLUSION:Based on the results of this study it can be concluded that alginate beads containing turmeric extract-PVP solid dispersion gives the stronger antibacterial activity than those containing turmeric extract without solid dispersion.

Bioadhesive or Mucoadhesive Drug Delivery System: A Potential Alternative to Conventional Therapy

The term bioadhesive describes materials that bind to biological substrates, such as mucosal membranes and in bioadhesive drug delivery systems, the term bioadhesion is used to describe the bonding or adhesion between a synthetic or natural polymer and soft tissues such as epithelial cells. The bioadhesive drug delivery formulation highlights the fact that readily accessible sites are utilized with the eye, oral cavity and vegina being targeted. The GI tract and the nasal cavity have also been extensively examined as a site for bioadhesive drug delivery. The term mucoadhesion is the subgroup of bioadhesion and in the mucoadhesion formulation attaches with the mucus membrane. The mucoadhesion can be defined as the adhesion between the two materials in which one is biological material and other one is polymeric materials with the help of interfacial forces to increase the residence time. Over the past few decades, mucosal drug delivery has received a great deal of attention. The mucoadhesion drug delivery system is better than the traditional drug delivery systems. Mucoadhesion is a useful strategy for drug delivery systems, such as tablets, patches, gels, liposomes, micro/nanoparticles, nanosuspensions, microemulsions and colloidal dispersions. The mucoadhesion bypasses the first pass metabolism and used for localized delivery of biomolecules such as peptides, proteins and oligonucleotides. Mucoadhesion drug delivery system engages much attention due to their benefits such as prolong retention time, fast uptake and increased bioavailability of active substance. Application of dosage forms to mucosal surfaces may be of benefit to drug molecules not amenable to the oral route, such as those that undergo acid degradation or extensive first-pass metabolism. The mucoadhesive ability of a dosage form is dependent upon a variety of factors, including the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various aspects of mucoadhesion, theories of mucoadhesion, mucoadhesive materials, factors affecting mucoadhesion, evaluating methods, mucoadhesive polymers and herbal drugs. Keywords: Bioadhesive, bioadhesive drug delivery, Mucoadhesion, Patches, Herbal drugs

Thiolated hydroxypropyl-β-cyclodextrin as mucoadhesive excipient for oral delivery of budesonide in liquid paediatric formulation.

Budesonide (BUD) is a low water soluble (S0 = 5.028·10-5 M) corticosteroid used as preferred therapy for the treatment of Eosinophilic Esophagitis (EoE), a chronic allergic-immune condition with an increased incidence in the paediatric population. Currently there are no commercial medicines indicated for EoE, and, therefore, in the hospital pharmacy the BUD is extemporaneously formulated as viscous oral suspension at the initial dose of 1-2 mg per day for children, highlighting the need of a mucoadhesive drug delivery system (MDDS) that adheres to the site of action and prolongs the therapeutic activity of the administered drug. Considering the ability of hydroxypropyl-β-cyclodextrin (HP-β-CD, 100 mM) to increase the water solubility of BUD (SHP-β-CD = 4.3·10-3 M; K1:1 = 861.11 M-1), a mucoadhesive thiolated HP-β-CD (HP-β-CD-SH) was synthesized and characterized by mass spectroscopy, 1H- and 13C NMR techniques. Phase-solubility studies demonstrated the capability of HP-β-CD-SH (100 mM) to form a reversible water soluble inclusion complex with BUD (SHP-β-CD-SH = 10.9·10-3 M; K1:1 = 2013.52 M-1), which increases its permanence on the target site as proved by mucoadhesive studies on porcine oesophagus mucosa. HP-β-CD-SH might be a useful MDDS for the pharmacist to prepare BUD oral liquid formulations at the recommended doses, with pH values below 5, which guarantee the chemical stability of the new mucoadhesive excipient.

Poly (Methacrylic Acid)-Grafted-Okra Gum: Synthesis, Characterization and Evaluation as Mucoadhesive

Recently, worldwide extensive attention is being paid in exploration and exploitation of pharmaceutical excipients from natural resource. Various natural polysaccharides have been significantly reported as prospective drug delivery carriers. These natural gums are preferred over synthetic polymers because of their biocompatibility, low cost, free availability and biodegradability. But due to variable chemical composition, microbial load, microbial growth and hange in viscosity upon aging, acceptability is low compared to commercial synthetic products. Tailoring or modification may be an approach to make them smart as drug carriers specially in order to modulate the site of drug release and it’s kinetic. The chemical modification of okra gum (OG) was the main objective of the present study in order to make it potential mucoadhesive for the application in mucoadhesive drug delivery. In this study, methacrylic acid was grafted onto okra gum. At first, okra gum has been isolated from the fruits of Hibiscus esculentus. Poly (methacrylic acid)-grafted-okra gum (PMAc-g-OG) was synthesized employing a microwave- promoted and redox-initiated method. Potassium persulphate was used as free- radical-initiator. Methacrylic acid was mixed to 1% solution of OG and then 30 ml of potassium per sulphate aqueous solution was added to the previous mixture along with continuous stirring. The mixture was exposed to microwave in a domestic micro-oven. The mixture was kept overnight and the copolymer was collected and purified using acetone and aqueous methanol (30% v/v) subsequently. The copolymer was characterized by elemental analysis, FTIR, DSC-TGA, and 13C NMR study. Ex-vivo mucoadhesion test was performed using goat stomach. A highest % grafting of 448.32% was found in the synthetic procedure employed in the study. The characterization studies also substantiate the successful grafting. Ex-vivo mucoadhesion study also showed excellent mucoadhesive capacity over a period of 16 hours. The study exhibited that the method employed was very simple, less time consuming, one-pot and without N2 atmosphere. The copolymer also exhibited excellent mucoadhesivity which might be applied in different mucoadhesive drug delivery systems such as prolonged release gastroretentives, buccal gels, etc.

Mucoadhesive Multiparticulate Drug Delivery Systems: An Extensive Review of Patents.

Innovations in pharmaceutical research are striving for designing newer drug therapies to eradicate deadly diseases. Strategies for such inventions always flourish with keys and objectives of minimal adverse effects and effective treatment. Recent trends in pharmaceutical technology specify that mucoadhesive drug delivery system is particularly appropriate than oral control release, for getting local systematic delivery of drugs in GIT for an extended interval of time at a predetermined rate. However, it is somehow expensive and unpleasant sensation for some patients, but still it is needful for getting short enzymatic activity, simple administration without pain and evasion of fast pass metabolism. Usually the vehicles employed in drug delivery of mucoadhesive system have a significant impact that draws further attention to potential benefits like improved bioavailability of therapeutic agents, extensive drug residence time at the site of administration and a comparatively faster drug uptake into the systemic circulation. The drug release from mucoadhesive multiparticulates is contingent on several types of factors comprising carrier need to produce the multiparticles and quantity of medication drug contained in them. Mucoadhesion is characterized by selected theories and mechanisms. Various strategies emergent in mucoadhesive multiparticulate drug delivery system (MMDDS) by in-vitro as well as ex-vivo description and characterization are also critically discussed. Apart from these, the primary focus during this review is to highlight current patents, clinical status, and regulatory policy for enhancement of mucoadhesive multi-particulate drug delivery system in the present scenario.

Mucoadhesive micro-composites: Chitosan coated halloysite nanotubes for sustained drug delivery

It was aim of this study to synthesize micro-composites comprising halloysite nanotubes (HNTs) and the cationic polymer chitosan as mucoadhesive sustained release drug delivery system. Micro-composites were characterized for preparation yield, size, micromeritic properties and swelling behavior. Chemical composition of micro-composites was characterized by FTIR, XRD and TGA. Scanning electron microscopy (SEM) was used to study their surface morphology. Micro-composites were studied for adhesion on intestinal mucosa as well as for release behavior of metoclopramide hydrochloride used as model drug. Preparation yield was found to be in the range of 35.14 ± 1.5–53.97 ± 5.23%. Micro-composites exhibited a mean size range of 0.151 ± 0.49 μm. SEM showed a spherical shape with rough curved porous surface. Micro-composites exhibited excellent flowability and maximum swelling at acidic pH. XRD results showed crystalline nature of micro-composites. HNTs/micro-composites with highest concentration of chitosan displayed maximum adherence of 89 ± 1.79% on intestinal mucosa after 3 h. Drug release recorded was 66.8% at pH 1.2 and 46.7% at pH 5.5 within 25 h. Chitosan coated HNTs showed remarkable mucoadhesion and sustained release of metoclopramide proving their suitability as mucoadhesive drug delivery system.

Phenylboronic acid-tethered chondroitin sulfate-based mucoadhesive nanostructured lipid carriers for the treatment of dry eye syndrome

Dry eye syndrome is a common eye disease that affects many people worldwide. It is usually treated with eye drops, which has low bioavailability owing to rapid clearance from the ocular surface and leads to poor patient compliance and side effects. For the purpose of improving the therapeutic efficacy, nanostructured lipid carrier (NLC)-loaded dexamethasone (DEX) was prepared and functionalized with (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS). As APBA has a boronic acid group, it can form a high-affinity complex with sialic acids present in the ocular mucin, which contributes to extension of corneal retention time and improvement of drug delivery. Compared with eye drops, Rhodamine B (RhB)-labeled APBA-ChS-NLC could significantly prolong the residence time on the corneal surface. Moreover, the DEX-APBA-ChS-NLC showed no irritation to the rabbit eye as indicated in irritation studies and histological images. The pharmacodynamics study indicated that DEX-APBA-ChS-NLC could relieve symptoms of dry eye disease in rabbits. These results demonstrated that the developed mucoadhesive drug carrier could improve the delivery of drugs and have promising potential to treat anterior eye diseases. Statement of SignificanceIn this research, (3-aminomethylphenyl)boronic acid-conjugated chondroitin sulfate (APBA-ChS)-based nanostructured lipid carriers (NLCs) including dexamethasone (DEX) were designed and constructed. APBA-ChS, which is present on the surface of DEX-NLC and contains the boronic acid group, can form complex with sialic acids in the ocular mucin, hence leading to prolonged precorneal retention. This affinity between boronic acid and sialic acids was used to develop a mucoadhesive drug delivery system. The developed mucoadhesive drug carrier demonstrated prolonged retention time and alleviation of dry eye syndrome. APBA-ChS-based NLC may be considered a promising ocular drug delivery system for treating anterior eye diseases.

Catechol-Functionalized Succinyl Chitosan for Novel Mucoadhesive Drug Delivery

The objective of this research was to synthesized and evaluated a mucoadhesive catechol-bearing succinyl chitosan (Cat-SCS) as an innovative mucoadhesive substance for a mucoadhesive drug delivery system. Succinyl chitosan (SCS) was synthesized via ring-opening reactions with succinic anhydride. The Cat-SCS was then synthesized by reacting SCS with dopamine with the existence of N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDAC) and N-hydroxysulfosuccinimide (NHS). The successful functionalization of catechol onto chitosan backbone was verified using nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FT-IR). Mucoadhesion studies were performed using rheology measurement and ex-vivo mucoadhesion test. The findings exposed that the synthesized Cat-SCS exhibited excellent mucoadhesive properties which was better than the intact CS. Further indirect studies verified the occurrence of polymer-mucin glycoproteins interactions. The catechol content of catechol moiety on the Cat-SCS was determined to be 0.377 using the 1H NMR. The cytotoxicity test indicated the biocompatibility of the obtained polymer on human gingival fibroblast cells (HGF cells). Therefore, these results could advocate the capacity to use of Cat-SCS as an innovative mucoadhesive platform for mucoadhesive drug delivery.