Mucoadhesive Polymers Research Articles

Fabrication of multifunctional mucoadhesive buccal patch for drug delivery applications

Mucoadhesive buccal patch is a promising dosage form for a successful oral drug delivery, which provides unique advantages for various applications such as treatment of periodontal disease and postdental surgery disorders. The aim of this study is to synthesize a novel multifunctional mucoadhesive buccal patch in a multilayer reservoir design for therapeutic applications. The patches were fabricated through simultaneous electrospinning of chitosan/poly(vinylalcohol) (PVA)/ibuprofen and electrospraying of phenylalanine amino acid nanotubes (PhNTs) containing metronidazole into the electrospun mats through a layer-by-layer process. An electrospun poly(caprolactone) (PCL) was used as an impermeable backing layer to protect the mucoadhesive component from tongue movement and drug loss. Buccal patches were characterized using scanning electron microscopy (SEM) and field emission scanning electron microscopy (FESEM) and also evaluated in terms of physicomechanical parameters such as pH, weight, thickness, tensile strength, folding endurance, and mucoadhesive properties. The swelling index of the patches was examined with respect to the PVA/chitosan ratio. The effect of genipin addition to the electrospinning solution was also studied on mucoadhesive and swelling properties. The cell viability of buccal patches was assessed by methylthiazolydiphenyl-tetrazolium bromide test on L929 fibroblast cell line. The patch with an optimal amount of mucoadhesive polymers (PVA/chitosan 80:20) and crosslinking agent (0.05 g) indicated an ideal hemostatic activity along with antibacterial properties against Streptococcus mutans bacteria. The synthesized multifunctional mucoadhesive patch with a novel composition and design has a great potential for oral therapeutic applications.

Pharmaceutical Considerations of Nasal In-Situ Gel As A Drug Delivery System

In situ gelling drug delivery systems have gained enormous attention over the last decade. They are in a sol-state before administration, and they are capable of forming gels in response to different endogenous stimuli, such as temperature increase, pH change and the presence of ions. Such systems can be administered through different routes, to achieve local or systemic drug delivery and can also be successfully used as vehicles for drug-loaded nano- and microparticles. Natural, synthetic and/or semi-synthetic polymers with in situ gelling behaviour can be used alone, or in combination, for the preparation of such systems; the association with mucoadhesive polymers is highly desirable in order to further prolong the residence time at the site of action/absorption. Nasal drug delivery is a better alternative of oral and parental route due to high permeability of Nasal epithelium, rapid drug absorption, avoid Hepatic first pass metabolism, increased bioavailability of drug, minimized local and systemic side effects, Low dose required, Direct transport into systemic circulation and CNS is also possible (passing blood brain barrier), Improved patient compliance, Self-Medication is Possible, prevent Gastro intestinal tract Ulceration. Recently, it has been shown that many drugs have better bioavailability by nasal route than the oral route. Thus, this review focuses on nasal drug delivery, various aspects of nasal anatomy and physiology, nasal absorption mechanism, advantages & disadvantage composition of in situ gel, application and In-situ gels evaluations.

Mucoadhesive Delivery System: A Smart Way to Improve Bioavailability of Nutraceuticals.

The conventional oral administration of many nutraceuticals exhibits poor oral bioavailability due to the harsh gastric conditions and first-pass metabolism. Oral mucosa has been recognized as a potential site for the delivery of therapeutic compounds. The mucoadhesive formulation can adhere to the mucosal membrane through various interaction mechanisms and enhance the retention and permeability of bioactive compounds. Absorption of bioactive compounds from the mucosa can improve bioavailability, as this route bypasses the hepatic first-pass metabolism and transit through the gastrointestinal tract. The mucosal administration is convenient, simple to access, and reported for increasing the bioactive concentration in plasma. Many mucoadhesive polymers, emulsifiers, thickeners used for the pharmaceutical formulation are accepted in the food sector. Introducing mucoadhesive formulations specific to the nutraceutical sector will be a game-changer as we are still looking for different ways to improve the bioavailability of many bioactive compounds. This article describes the overview of buccal mucosa, the concept of mucoadhesion and related theories, and different techniques of mucoadhesive formulations. Finally, the classification of mucoadhesive polymers and the mucoadhesive systems designed for the effective delivery of bioactive compounds are presented.

Synthesis and Characterization of Thiolated Gum Ghatti as a Novel Excipient: Development of Compression-Coated Mucoadhesive Tablets of Domperidone.

Mucoadhesive polymers represent a major part of site-specific and localized retention strategies in oral drug delivery. The present research was designed to synthesize and characterize a novel mucoadhesive carbohydrate polymer (thiolated gum ghatti; TGG), which was employed to formulate mucoadhesive tablets of domperidone using an industrially viable compression coating technique. Thiolation of gum ghatti was achieved by the ester formation (esterification) between the hydroxyl group and the carboxyl group of gum ghatti and thioglycolic acid. TGG was characterized by various physicochemical techniques such as FTIR, XRD, SEM, and DSC. In rheological studies, the observed viscosities of pure gum mucin were 45.45 and 71.75 mPa·s and those of the thiolated gum were 78.7 and 112.58 mPa·s, respectively, in water and simulated gastric fluid. A significant increase in viscosity for thiolated gum may be attributed to increased macromolecular interactions responsible for enhanced mucoadhesive potential of thiolated gum. In silico studies corroborate the role of mucin gum interaction and energetic stabilization for enhanced mucoadhesion properties of thiolated gum. Ex vivo mucoadhesion strength of gum ghatti- and TGG-coated tablets was found to be ranging between 45.77 ± 1.49 and 88.16 ± 1.75 and 115.32 ± 2.36 and 184.65 ± 2.07 mN, respectively. In an acute oral toxicity study, TGG did not show any toxicity on the vital organs of the Wistar rat and proved to be a safe polymer. TGG may be regarded as a promising polymer for developing different mucoadhesive drug delivery systems.

Functionality and Acceptance of the EsoCap System-A Novel Film-Based Drug Delivery Technology: Results of an In Vivo Study.

There are no methods for specific local application of active substances to the mucosa of the esophagus to treat eosinophilic esophagitis or other esophageal diseases. This publication describes the principal in vivo functionality and acceptance of a novel modular drug delivery concept, called EsoCap system, by 12 healthy volunteers. For the first time, the EsoCap system enables targeted placement on the esophageal mucosa of a mucoadhesive polymer film. Acceptance was determined by means of a standardized questionnaire after administration and functionality of the device by MRI scans. Two different setups of the EsoCap system were tested: one setup with a density of 0.4 g/cm3 and one with a density of 1.0 g/cm3. Acceptability of the dosage form was also confirmed in addition to functionality, by measuring the applied film length. It was found that acceptance of the variant with the higher density was significantly better. This novel drug delivery technology could enable a targeted, local and long-lasting therapy of the esophagus for the first time, depending on the polymer film used.

A Glance on Mucoadhesive System - Still more to Understand

Most popular and useful route of administration is oral one, among that mucoadhesive system is also preferable. This system is interact with mucus layer containing epithelial cell and mucin molecules which improves the contact time of dosage form, leading to improvement in both local and systemic effects. There are various routes of mucoadhesive drug delivery system, oral route is the most oldest and preferred by patient being convenient to use. However peroral route has some disadvantages such as hepatic first pass metabolism and enzymatic degradation in GIT which is a hindrance to the absorption of most proteins and peptides groups of drugs. The mucosa of the oral cavity contains an intimidating barrier to drug penetration, and one method of optimizing drug delivery is by the use of adhesive dosage forms and the mucosa is connected with various blood supplies by which it is permeable. This route has quick action, and good patient compliance with pediatric and old age patients. The buccal cavity is very easier for a bioadhesion system because of a smooth and relatively immobile surface and accessibility. Mucoadhesion can be achieved by using various mucoadhesive polymers. There are various types of mucoadhesive polymers which improves bioadhesion. Also various theories are referred to clear the concept of mucoadhesion, such as diffusion, facture, electronic and adsorption theories. This article contains definition, mechanism, advantage, and disadvantage. In this article we are going to overlook basic knowledge about mucoadhesion and its formulations.

Design and Investigation of Alginate Coated Solid Lipid Nanoparticles for Oral Insulin Delivery

Abstract: Introduction: The conventional subcutaneous administration of insulin has been associated with several limitations leading to poor patient compliance. The poor oral bioavailability of insulin due to degradation by gastrointestinal enzymes and secretions can be countered by the use of protective carriers such as solid lipid nanoparticles that are capable of being taken up by the Peyer’s patches. The aim of the investigation was to design and investigate alginate coated solid lipid nanoparticles (SLN) of insulin for oral administration. Materials and Methods: The SLN were prepared from glyceryl behenate and glyceryl monostearate and coated with mucoadhesive polymer, sodium alginate. The SLN were evaluated for size, shape, zeta potential, drug content, in vitro release and ex vivo drug permeation through goat intestinal mucosa and Caco-2 cell monolayer model. Results and Discussion: Transmission electron microscopy revealed spherical particles of uniform size distribution. In vitro drug release using the reverse dialysis method revealed that the alginate coating maintained the potency of insulin in simulated GI fluids and also provided sustained release. Absorption enhancement was demonstrated in ex vivo permeation studies in the goat intestinal mucosal model as well as in the Caco-2 cell monolayer model. The oral administration of alginate-coated insulin SLN in streptozotocin induced diabetic rats resulted in a significant hypoglycemic effect as compared to that of uncoated insulin-loaded SLN. The percentage glycemia at the end of 10 h was statistically significant (p<0.05) to oral insulin and the hypoglycemic levels reached were comparable to that of the conventional subcutaneous insulin. Conclusion: Alginate coated SLN has the potential of improving the absorption of insulin through intestinal mucosa and possibly its bioavailability. Key words: Solid lipid nanoparticle, Insulin, Oral delivery, Sodium alginate, Glycerol monostearate, Hypoglycemia.

Design and in-vitro Evaluation of Float-adhesive Famotidine Microspheres by using Natural Polymers for Gastroretentive Properties

Abstract: Objectives: In the present investigation a novel oral drug delivery system was developed by combining two different techniques floating and mucoadhesive system so called floatadhesive, in order to obtain a controlled system that could remain in the stomach for prolonged period and release the drug in a controlled manner. Materials and Methods: Microspheres containing Famotidine were prepared by ionic gelation method using Mimosa pudica seed mucilage as a natural mucoadhesive polymer. Sodium alginate (SA) and chitosan (CS) were incorporated as drug release modifier. The microspheres were characterized by scanning electron microscopy and evaluated by employing shape and particle size, % drug entrapment efficiency, in vitro floating ability, in vitro mucoadhesion and in vitro drug release pattern. Results: The prepared microspheres were acceptably spherical with a mean particle size in the range of 334 ± 1.18 μm to 498 ± 1.12 μm. Drug entrapment efficiency was observed in the range of 72.82 ± 1.10% to 92.38 ± 1.20%. Formulations containing a combination of both mucilage and chitosan showed increased in vitro mucoadhesion and buoyancy as compared to formulations containing chitosan alone. In vitro drug release for all the formulations in 0.1N HCl was diffusion controlled gradually throughout 12 h and followed Higuchi’s and Korsmeyer Peppas kinetics. The mechanism of in vitro drug release was non-fickian type controlled by swelling and relaxation of the polymer. Conclusion: The developed microspheres have dual advantages of being floating and mucoadhesive to increase oral bioavailability and releasing drug in a controlled manner, to reduce the required frequency of administration thereby promoting patient compliance. Key words: Natural polymers, Mimosa pudica mucilage, Chitosan, Floating, Mucoadhesive, Float-adhesive, Ionic gelation.

Feasibility of chitosan-based nanoparticles approach for intranasal immunisation of live attenuated Japanese encephalitis vaccine

Intranasal (IN) administration, a non-invasive route, is explored to overcome the limitations of conventional subcutaneous (SC) injection for Japanese encephalitis (JE) immunisation. Mucoadhesive nanoparticles (NPs) are recognised for the benefits they offer via IN delivery, such as extended retention time of the vaccine on the mucosa. The purpose of this study was to evaluate immunisation effect of live attenuated Japanese encephalitis-chimeric virus vaccine (JE-CV)-loaded mucoadhesive NPs based on chitosan (CS) or chitosan maleimide (CM), a novel mucoadhesive polymer, via the IN route to improve the mucosal immunisation against JE. The results revealed that IN immunisation stimulated seroprotection following PRNT50 evaluation. Moreover, compared with SC immunisation, IN immunisation in mice provided a higher sIgA level, leading to improved mucosal immune response. In addition, chitosan-based NPs showed an adjuvant effect on the IN vaccine due to their mucoadhesive and antigen-uptaken properties. CM NPs successfully induced sIgA. In contrast, SC JE-CV immunisation induced negligible mucosal immunity. These immunological advantages revealed that JE-CV-loaded mucoadhesive NPs are a promising approach for IN vaccination as an alternative route for JE protection due to the stimulatory effects on both mucosal and systemic immune responses.

Development of Intranasal Levothyroxine Powder Delivery for Hypothyroidism

Background: Hypothyroidism affects 3-5% of the general population with oral levothyroxine (LT4) being the predominant replacement therapy. However, significant proportion of hypothyroid patients are unable to absorb oral replacement leading to therapeutic failure and may require injectable thyroxine. Objectives: To develop non-invasive, less costly, and patient-friendly LT4 nasal delivery alternative using mucoadhesive polymers: chitosan and hydroxypropylmethylcellulose (HPMC). Methods: Six nasal LT4 formulations were developed with either chitosan or hydroxypropyl methylcellulose as mucoadhesive. The formulations were prepared through freeze-drying by varying the drug to polymer ratio (1:1, 1:3, and 1:5). The percentage drug yield was calculated by analyzing the weight of the formulation pre- and post-freeze drying. HPLC analysis was conducted to determine the amount of LT4 loaded in each formulation. Furthermore, the surface morphology, particle size, zeta potential, differential scanning calorimetry, X-ray diffraction as well as the in vitro release were assessed to determine the physicochemical properties and release characteristics of the formulations, respectively. Results: Both percentage drug loading and yield were > 70% for all the formulations. The freeze-dried formulations displayed a compact needle-like surface morphology. LT4-chitosan formulations, 1:1, 1:3, and 1:5 had mean particle size of 2.45 ± 0.88 µm, 2.76 ± 1.38 µm, and 1.59 ± 0.27 µm, respectively. Mean particle sizes for 1:1, 1:3, and 1:5 LT4-HPMC formulations were 0.56 ± 0.02 µm, 0.22 ± 0.06 µm, and 0.46 ± 0.04 µm. Zeta potential for LT4-chitosan formulation 1:1, 1:3, and 1:5 were -18.7 ± 1.00 mV, -16.2 ± 0.79 mV, and -19.17 ± 1.01 mV, respectively. LT4-HPMC 1:1, 1:3, and 1:5 formulations had zeta charges of -11.66 ± 3.16 mV, -6.06 ± 3.92 mV, and -9.53 ± 1.68 mV, respectively. Differential calorimetric analysis confirmed drug-polymer integration in all formulations, and X-ray powder diffraction showed both chitosan and HPMC formulations as crystalline configuration. The formulations with the highest in vitro release were LT4-HPMC 1:3 and LT4-chitosan 1:5. Conclusions: Results of this study suggest that both chitosan and HPMC can be used as sustained release polymers for the intranasal delivery of LT4.

Development and in vitro Characterization of Intranasal Microemulsions of Sumatriptan Succinate for brain Targeting

Microemulsions, by virtue of their lipophilic nature and low globule size, are widely explored as a delivery system to enhance uptake across mucosa. The main aim of the present investigation is to develop and in vitro characterization of intra nasal microemulsion of sumatriptan succinate for brain targeting for treating acute attack of migraine. The liquid microemulsion was prepared by dissolving drug (sumatriptan succinate) and mucoadhesive polymer sodium alginate in double distilled water. The prepared microemulsion was evaluated for particle size measurement, zeta potential measurement, viscosity measurement, centrifugation, drug content, optical clarity and in vitro drug release studies. The prepared formulations were showed particle size in the range of 106.2±2.03 to 282.8±2.51. The zeta potential value of the formulation ME2 showed −32.0mv indicating negative surface charge. The drug content showed in the range of 89.3±0.242 to 94.3±0.128. the optimized formulation showed in vitro drug release 74.2±0.95% at 12 h. and 86.23±0.41% at 24 hrs. From the results it was concluded that the prepared optimized microemulsion formulation as drug delivery system to improve bioavailability of the drugs like sumatriptan succinate.

Formulation and Optimization of Sodium Alginate Polymer Film as a Buccal Mucoadhesive Drug Delivery System Containing Cetirizine Dihydrochloride.

Currently, pharmaceutical companies are working on innovative methods, processes and products. Oral mucoadhesive systems, such as tablets, gels, and polymer films, are among these possible products. Oral mucoadhesive systems possess many advantages, including the possibility to be applied in swallowing problems. The present study focused on formulating buccal mucoadhesive polymer films and investigating the physical and physical–chemical properties of films. Sodium alginate (SA) and hydroxypropyl methylcellulose (HPMC) were used as film-forming agents, glycerol (GLY) was added as a plasticizer, and cetirizine dihydrochloride (CTZ) was used as an active pharmaceutical ingredient (API). The polymer films were prepared at room temperature with the solvent casting method by mixed two-level and three-level factorial designs. The thickness, tensile strength (hardness), mucoadhesivity, surface free energy (SFE), FTIR, and Raman spectra, as well as the dissolution of the prepared films, were investigated. The investigations showed that GLY can reduce the mucoadhesivity of films, and CTZ can increase the tensile strength of films. The distribution of CTZ proved to be homogeneous in the films. The API could dissolve completely from all the films. We can conclude that polymer films with 1% and 3% GLY concentrations are appropriate to be formulated for application on the buccal mucosa as a drug delivery system.

Mucoadhesive polymers for buccal drug delivery system: An overview

Pharmaceutical scientists around the globe have been seeking to discover as an alternative to injections over the last few, transdermal and transmucosal routes decades. The buccal cavity mucosa the most convenient and easily available site for the distribution of local and systemic therapeutic agents was found to be dosage forms among the numerous transmucosal sitesavailable.Theories and various polymers used in mucoadhesive drug delivery. Mucoadhesive polymers increases the residence time, prolong the absorption, enhances solubilityand dissolution characteristics of poorly soluble drugs. In addition, we are focused on the latest generation of mucoadhesion polymers, led by the latest formulation of mucoadhesive for the distribution of oral drugs, such as thiolated polymers. A good insight into mucoadhesion polymers, the mucoadhesive phenomenon and the factors that can affect polymer mucoadhesion is given in the current analysis. The systematic drug delivery has been investigated for buccal mucosa and local drug treatment or therapy is subjected to first pass metabolism. Oral mucosa drug delivery by discussing the structural features of mucosa, mechanism of mucoadhesion. General consideration in design of mucoadhesive buccal dosage forms, permeation enhancers and the various evalution method along with literature survey of the buccal mucoadhesive.&#x0D;

Bioadhesive-Thermosensitive In Situ Vaginal Gel of the Gel Flake-Solid Dispersion of Itraconazole for Enhanced Antifungal Activity in the Treatment of Vaginal Candidiasis.

The poor solubility of itraconazole (ITZ) has limited its efficacy in the treatment of vaginal candidiasis. Accordingly, the improvement of ITZ solubility using a solid dispersion technique was important to enhance its antifungal activity. Besides, as the purpose of this research was to develop local-targeting formulations, bioadhesive-thermosensitive in situ vaginal gel combined with the gel-flake system was found to be the most suitable choice. To obtain optimum solubility, entrapment efficiency, and drug-loading capacity, optimization of solid dispersion (SD) and gel-flake formulations of ITZ was performed using a composite central design. The results showed that the optimized formulation of SD-ITZ was able to significantly enhance its solubility in both water and simulated vaginal fluid to reach the values of 4.211 ± 0.23 and 4.291 ± 0.21 mg/mL, respectively. Additionally, the optimized formulation of SD-ITZ gel flakes possessed desirable entrapment efficiency and drug-loading capacity. The in situ vaginal gel containing SD-ITZ gel flakes was prepared using PF-127 and PF-68, as the gelling agents, with the addition of hydroxypropyl methylcellulose (HPMC) as the mucoadhesive polymer. It was found that the obtained in situ vaginal gel provided desirable physicochemical properties and was able to retain an amount of more than 4 mg of ITZ in the vaginal tissue after 8 h. Importantly, according to the in vivo antifungal activity using infection animal models, the incorporation of the solid dispersion technique and gel-flake system in the formulation of the bioadhesive-thermosensitive in situ vaginal gel led to the most significant decrease of the growth of Candida albicans reaching <1 log colony-forming units (CFU)/mL or equivalent to <10% of the total colony after 14 days, indicating the improvement of ITZ antifungal activity compared to other treated groups. Therefore, these studies confirmed a great potential to enhance the efficacy of ITZ in treating vaginal candidiasis. Following these findings, several further experiments need to be performed to ensure acceptability and usability before the research reaches the clinical stage.

MUCOADHESIVE BUCCAL FILMS: A NOVEL APPROACH FOR THE DELIVERY OF ANTI-HYPERTENSIVE DRUGS

The buccal drug delivery system is a prominent route of administration for drug delivery through the buccal mucosa. It is rich in blood supply with more surface area for rapid absorption as well as provides direct entry of drugs from the site of application into the systemic circulation through the jugular vein. Buccal drug delivery systems consist of various approaches such as lozenges, wafers, gels, microparticles, patches or films from which mucoadhesive buccal film is an attractive dosage form in terms of flexibility and high systemic bioavailability. Since most of the antihypertensive drugs show first-pass metabolism which leads to less oral bioavailability generally up to 20–50%. Thus, incorporation of antihypertensive drugs in mucoadhesive buccal films using mucoadhesive polymers can provide higher systemic bioavailability. The films can be formulated using various techniques such as solvent casting method and hot extrusion melt method. These films can be evaluated based on various characteristics to determine their efficacy and performance such as tensile strength, mucoadhesion residence time, and kinetic release data analysis. They have various advantages over conventional solid oral dosage forms, hence are preferable for the preparation of antihypertensive drug-loaded buccal films. Mucoadhesive buccal films of antihypertensive drugs can also provide controlled drug delivery with enhanced bioavailability.

Clarithromycin Loaded Chitosan Nanoparticles: Development and Characterization

Background:: Chitosan nanoparticles have been extensively studied and used due to their well-recognized applicability in various fields. Chitosan, a natural polysaccharide polymer, is extensively used in pharmaceuticals to deliver a wide variety of therapeutic agents. Chitosan is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of multi particles, particularly nano- and microparticles. Objective:: The main aim of the present study was to optimize the conditions for the preparation of chitosan nanoparticles to get optimal particle size, with optimal zeta potential and narrow polydispersity index and anti-bacterial activity. Methods:: Include the ionic gelation technique for chitosan nanoparticle preparation. The influence of formulation parameters and process parameters on the chitosan nanoparticles were investigated. Besides, the suspension stability of the prepared nanoparticles was also assessed on storage at 4°C. Results: The formulation and process parameters showed a significant effect on the physicochemical and morphological characteristics of the chitosan nanoparticles. The chitosan nanoparticles prepared under optimum conditions (chitosan concentration of 0.5% w/v, CS: TPP mass ratio of 1:3, initial pH of chitosan solution of 4.5, stirred at 750 rpm for 30 min) had shown a mean particle size of ~326.8±15 nm, zeta potential of +28.2 ± 0.5 mV, and PDI of 0.21 ± 0.02. The encapsulation of the clarithromycin slightly increased the polydispersity index, but the zeta potential of the unloaded nanoparticles was not affected while the particle size increased. Under optimum conditions, clarithromycin encapsulation efficiency into nanoparticles was found to be 70%. Additionally, chitosan- tripolyphosphate nanoparticles were shown to be stable for a minimum of fifteen days in deionized water at 4°C. Conclusion:: The current study concludes the optimal conditions to formulate the chitosan nanoparticles with optimal physicochemical characteristics.

Development and Characterization of Mitoxantrone-Loaded Glutaraldehyde Crosslinked Sodium Alginate Nanoparticles for the Delivery of Anticancer Drugs

Every year millions of new cases of various types of cancers are diagnosed, leading to an alarming rate of fatalities. Mitoxantrone is an anthracenedione antineoplastic agent which is used in the treatment of various types of cancer, mostly acute myeloid leukemia and prostate cancer. In spite of its therapeutic applications, it possesses numerous limitations and side effects including specific targeting and systemic toxicity. Sodium alginate is a biodegradable, mucoadhesive and biocompatible polymer commonly used in drug delivery applications. Glutaraldehyde is a saturated dialdehyde and is used as a polymer cross linker. In this study, mitoxantrone-loaded glutaraldehyde-sodium alginate nanoparticles were developed by ionic gelation method and characterized (determination of particle size, drug entrapment efficiency, drug release and its kinetics) for the delivery of anticancer drugs. The nanoparticles mean particle size was found to be within the acceptable range. The entrapment efficiency was also on the higher side with sustained drug release. The findings of this study reveal promising potential of delivery system and project the way forward for further in vitro and in vivo investigations.

Gut Microbe-Derived Outer Membrane Vesicles: A Potential Platform to Control Cecal Load of Campylobacter jejuni.

Acute diarrheal illness and gastroenteritis caused by Campylobacter jejuni infection remain significant public health risks in developing countries with substantial mortality and morbidity in humans, particularly in children under the age of five. Genetic diversities among Campylobacter jejuni and limited understanding of immunological correlations of host protection remain primary impediments for developing an effective measure to controlCampylobacter infection. Moreover, the lack of a reliable in vivo model to mimic natural infection against Campylobacter jejuni has substantially delayed the vaccine-development process. Given the role of bacterial outer membrane associated proteins in intestinal adherence and invasion as well as modulating dynamic interplay between host and pathogens, bacterial outer-membrane vesicles have emerged as a potential vaccine target against a number of gut pathogens, including Campylobacter jejuni. Here, we describe a mucosal vaccine strategy using chitosan-coated outer-membrane vesicles to induce specific immune responses against Campylobacter jejuni in mice. To overcome the challenges of mucosal delivery of outer membrane vesicles in terms of exposure to variable pH and risk of enzymatic degradation, we preferentially used chitosan as a nontoxic, mucoadhesive polymer. We show that intragastric delivery of chitosan-coated outer-membrane vesicles imparts significant immune protection against Campylobacter jejuni with high level local and systemic antibody production. Further, immunization with the outer membrane vesicles resulted in potent cellular responses with an increased CD4+ and CD8+ T cell population. Moreover, significant upregulation of IFN-γ and IL-6 gene expression suggests that mucosal delivery of outer membrane vesicles promotes a Th1/Th2 mixed-type immune response. Together, as an acellular and nonreplicating canonical end product of bacterial secretion, mucosal delivery of outer membrane vesicles may represent a promising platform for developing an effective vaccine againstCampylobacter jejuni.

Current Status of Mucoadhesive Gel Systems for Buccal Drug Delivery.

Buccal drug delivery is a fascinating research field. Gel-based formulations present potent characteristics as buccal systems since they have great physicochemical properties. Among the various gels, in situ gels are viscous colloidal systems consisting of polymers; when physiological conditions change (pH, temperature, ion activation), they are transformed into the gel phase. These systems can improve bioavailability. Other systems, such as nanogels or emulgels can also be applied for buccal delivery with promising results. Polymeric gel-based systems can be produced by natural, semisynthetic, and synthetic polymers. Their main advantage is that the active molecules can be released in a sustained and controllable manner. Several gels based on chitosan are produced for the entrapment of drugs demonstrating efficient retention time and bioavailability due to chitosan mucoadhesion. Besides polysaccharides, poloxamers and carbopol are also used in buccal gels due to their high swelling ability and reversed thermal gelation behavior. Herein, the authors focused on the current development of mucoadhesive gel systems used in buccal drug delivery. After explaining buccal drug delivery and mucoadhesion, various studies with hydrogels, in situ gels, and nanogels were analyzed as buccal gel systems. Various mucoadhesive gel studies with mucoadhesive polymers have been studied and summarized. This review is presented as valuable guidance to scientists in formulating buccal mucoadhesive drug delivery systems. This review aimed to assist researchers working on buccal drug delivery by summarizing buccal drug delivery, mucoadhesion, and buccal mucoadhesive gel systems recently found in the literature.

Oral Insulin Delivery by Chitosan Coated Solid Lipid Nanoparticles: Ex vivo and in vivo Studies

<p style="text-align: justify;"><strong>Objectives: </strong>The objective of this investigation was to formulate chitosan coated, insulin-loaded solid lipid nanoparticles (SLN) for oral administration and investigate their potential as an effective alternative to the subcutaneous injection. <strong>Methods: </strong>The SLN were prepared from glyceryl monostearate and coated with the mucoadhesive polymer, chitosan and were investigated for physical properties, <em>ex vivo</em> permeation through Caco-2-cell monolayer and goat intestinal mucosa. The<em> in vivo</em> efficacy of the optimized formulation in controlling blood glucose levels was studied in streptozotocin induced diabetic rats.<strong> Results: </strong>Coating in the presence of Poloxamer 407 resulted in significantly smaller nanoparticles than those with Tween 80. Scanning electron microscopy and transmission electron microscopy revealed spherical particles of uniform size distribution. The insulin association efficiency and loading efficiency of SLN prepared with Poloxamer were much greater than those with Tween 80. <em>Ex vivo p</em>ermeability studies in Caco-2 cell monolayer revealed a 4 fold increase in insulin permeation from chitosan coated SLN (<em>P</em>&lt; 0.005) as compared to uncoated SLN at the end of 6 h. The percentage permeation through excised sheep intestinal mucosa from coated SLN was twice that from uncoated SLN and nearly 20 times from insulin solution. The oral administration of chitosan-coated insulin SLN to streptozotocin-induced diabetic rats resulted in a significant hypoglycemic effect (<em>P</em>&lt;0.05) when compared to the groups that received uncoated insulin-loaded SLN or the oral insulin solution and was comparable to that of subcutaneous insulin at the end of an 8 h study. <strong>Conclusion:</strong> Chitosan coated SLN can be considered promising as an effective oral insulin formulation. <p style="text-align: justify;"><strong>Key words:</strong> Chitosan, Diabetes, Glyceryl monostearate, Insulin, Nanoparticles, Permeation.