Mucoadhesive Patches Research Articles

A mucoadhesive patch loaded with freeze-dried liposomes for the local treatment of oral tumors.

Oral cancers affect millions of people globally, with increasing incidences among adults aged 35 and above. Poor drug uptake by lesions in the oral cavity following systemic administration, as well as limited localized treatment modalities for oral tumors, result in poor patient quality of life and high mortality. Here, we describe a solid, dissolvable, bioadhesive alginate patch containing freeze-dried doxorubicin-loaded liposomes as a local treatment for oral tumors located on the tongue. By varying the alginate-to-liposome ratio in the mucoadhesive patch, we could control the degree of bioadhesion to the tongue and the release profile of the drug-loaded liposomes from the matrix. In vitro, exposing squamous cell carcinoma (SCC) to the alginate mucoadhesive patch or tablet resulted in dose-dependent cancer-cell death. In vivo, the efficacy of the local treatment was demonstrated in mice bearing orthotopic SCC tumors in the tongue. The bioadhesive patch, applied directly above the lesion, significantly reduced the tumor size and treatment-associated side effects compared to implanted patches or systemic drug administration. This study demonstrates that local bioadhesive therapies are effective in treating cancers of the oral cavity.

MUCOADHESIVE PATCHES OF PREGABALIN EFFECTIVE IN THE TREATMENT OF NEUROPATHIC PAIN: A SYSTEMATIC REVIEW

Although the oral pathway is the recommended mode of intake for the majority of medications, it does have some drawbacks i.e., pre-systemic metabolism in the liver, gastrointestinal disturbance, and enzyme degradation. It offers a safe method for administration of medications and easy way to reverse the intake of toxic substances by easy removal of dosage form from oral cavity. This review was designed to critically acknowledge the evaluation parameters, mechanism of cohesion, polymers used in mucoadhesive formulation, main method of preparations (solvent casting & milling), advantages & disadvantages of mucoadhesive patches. This review consists an extensive survey of literature from the Scopus, PubMed, Springer Nature and other international reputed sources. Since the middle of 1980s, the idea of muco-adhesion has acquired extensive interest in drug innovation. Muco-adhesive dosage structures were developed for oral delivery like adhesive unit dosage form, adhesive gels and adhesive patches. The epithelium that forms the internal lining of buccal mucosa is the primary obstruction for the drugs absorption. Muco-adhesion is defined as an interfacial adhesion in which one synthetic mucoadhesive polymer and the other mucin layer (mucosal tissue), are hold together by an attraction force. 'Mucoadhesive’ is defined as an artificial substance being capable of making interaction with mucus membranes and binding them together for extended or delayed periods of time. However, delivering therapeutically for the therapy of both systemic and topical disorders would take a lot more work with these innovative mucoadhesive formulations. In conclusion, it facilitates the target therapy by enriching efficacy or intrinsic activity. Keywords: mucoadhesive patch, solvent-casting, milling, mechanism of muco-adhesion, polymers

Epigallocatechin gallate Mucoadhesive Gingival Patch as Potential Biomaterial to Regulate Macrophage and Lymphocyte Cells in Periodontitis: A Review

Background: Periodontitis is a periodontal disease that affects more than 743 million peopleworldwide and causes damage to the periodontal ligament and alveolar bone. One of the bacteriathat can cause periodontitis is Porphyromonas gingivalis (P.gingivalis). P. gingivalis has virulence factors that can damage the periodontal tissue. Treatment of periodontitis is in the form of non- surgical therapy such as scaling and root planning and some cases, doxycycline can be given as adjunctive therapy after scaling and root planing. Epigallocatechin gallate (EGCG) is one of the catechins found in green tea and has anti-bacterial properties. Purpose: The study aimed to describe the potency of the mucoadhesive gingival patch with EGCG green tea against the number of macrophage cells and lymphocyte cells during periodontitis through narrative review. Review: Mucoadhesive gingiva patch loaded with EGCG has the advantages such as maintaining drug bioavailability, non-invasive, and optimizing drug distribution. Using a mucoadhesive gingiva patch with EGCG can reduce macrophage and lymphocyte cells by inhibiting lipopolysaccharide, a virulence factor of P. gingivalis. Inhibited lipopolysaccharide will inhibit pro-inflammatory cytokines such as TNF-α and IL-6. Macrophage and lymphocyte cells will reduce due to the inhibition of pro inflammatory cytokines. Conclusion: Mucoadhesive gingiva patch with EGCG green tea potentially to decreased macrophage and lymphocyte cells in periodontitis.

Evaluation of cinnamaldehyde mucoadhesive patches on minor recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled clinical trial

Background & objectiveThe use of herbal medicines to treat common oral diseases increases rapidly. Recurrent aphthous stomatitis is one of the most common oral mucosal diseases, which has an unclear etiology and could lead to severe pain and dysfunction. Cinnamaldehyde is a major component of cinnamon bark oil. Biological properties of cinnamaldehyde, such as antioxidant, antitumor, antifungal, cytotoxic, and anti-mutational characteristics, have been identified. Considering the prevalence of recurrent aphthous stomatitis and the importance of using herbal resources for treatment, the present study aimed to evaluate the effect of mucosal adhesive patches containing Cinnamaldehyde on minor recurrent aphthous stomatitis lesions.Material & methodsIn this randomized, double-blind clinical trial, patients were divided into two groups. The intervention group received three daily mucosal adhesive patches to be used in the morning, afternoon, and night. The control group also did the same with a placebo. To evaluate the healing and determine the diameter of the lesions, patients were clinically examined on days zero, 3, 5, and 7. The VAS scale evaluated pain at baseline and after each meal for seven days. The Fisher's exact test, t-test, Shapiro Wilk test, Friedman test, and the Mann–Whitney test were used to analyze the data using the SPSS 20 software.ResultsThere was no statistically significant difference in the mean diameter of the inflammatory lesion and pain intensity in the two groups in the baseline (p > 0.05). However, the ulcer size was significantly reduced in the cinnamaldehyde group on the third, fifth, and seventh days of the study. Except for baseline, the mean pain intensity significantly decreased in the cinnamaldehyde group compared to the placebo group (p < 0.05).ConclusionCinnamaldehyde mucoadhesive patches effectively reduced and improved aphthous lesions and pain intensity in patients and can be considered a treatment for RAS. Registration number: IRCT20180312039060N2—First registration date: 20/07/2018. The present study was registered as a retrospective study.

The effect of thiol functional groups on bovine serum albumin/chitosan buccal mucoadhesive patches

In this research, the effect of thiol functional groups on bovine serum albumin (BSA)/chitosan (Chi) based buccal mucoadhesive patch was investigated. Thiolated BSA (BSA-SH) was prepared via 2-mercaptoethanol. FTIR and 1H NMR results confirmed that BSA-SH was synthesized successfully. The buccal mucoadhesive patches were fabricated by the solvent casting method. Following the structural characterization of BSA/Chi and BSA-SH/Chi buccal patches, the mechanical characterization was performed by tensile tests. The drug release from triamcinolone acetonide (TR) loaded buccal patches was evaluated in-vitro in simulated salivary. According to the ex-vivo buccal adhesion experiments, the mechanical and mucoadhesion properties of BSA-SH/Chi buccal patch had improved compared to BSA/Chi buccal patch. The total cumulative TR permeated after 12 h was higher for BSA-SH/Chi than BSA/Chi buccal patches. The developed mucoadhesive buccal patches were found to be biocompatible in vitro. To conclude, the thiolated BSA-SH/Chi buccal adhesive patch is a promising biomaterial for a satisfied drug delivery, which provides advantages for various oral applications.

A Novel Capsule-Delivered Enteric Drug-Injection Device for Delivery of Systemic Biologics: A Pilot Study in a Porcine Model.

Innovative swallowable capsule technologies such as drug-loaded, dissolvable microneedles, mucoadhesive patches, and various microdevices present unique drug-carrying capabilities to overcome challenges regarding oral delivery of biologics. Here, we report a swallowable capsule for intestinal drug delivery (SCIDD) with the potential of directly injecting biological therapeutics into the insensate small intestine wall. The design, optimization, and validation of the SCIDD's primary subsystems were performed both ex-vivo and in-vivo. The assembled capsule was further tested in vivo to validate the actuation sequence and showed a 70% (n = 17) success rate in an animal model. Additionally, a drug delivery study indicated systemic uptake of adalimumab via SCIDD compared with luminal delivery in the small intestine. The pilot study presented here establishes that the novel platform could be used to orally deliver systemic biologics.

The effects of licorice mucoadhesive patches (Aftogel®) on the results of nasopharyngeal swab real-time PCR test of SARS-CoV-2: a randomized triple-blind placebo-controlled clinical trial

Background and objectives: Up to present no efficacious antiviral medications have been discovered in order to eradicate SARS-CoV-2 in nasopharyngeal tract. In this article, the aim is to evaluate the effectiveness of a new herbal drug product called Aftogel patch, which contains licorice extract, in the eradication of this novel coronavirus in the nasopharyngeal secretions of the patients. Methods: In this triple-blind randomized clinical trial, 125 patients with positive real-time PCR for SARS-CoV-2 and in stage 0 and/or 1 of COVID-19 were studied in two separate groups, namely interventional and placebo, in which they used Aftogel and placebo patches, respectively. At the end of the study, the results of PCR test in aforementioned groups were assessed and compared. Results: Following the application of Aftogel, Real-time PCR was converted to negative in 53.97% of patients which was significantly higher than that of the placebo groups. (27.40%, P= 0.003). Conclusion: It seems that Aftogel mucoadhesive patch (Licorice extract) is effective in the eradication of SARS-CoV-2 which has colonized the nasopharyngeal area. Hence, this drug product has the potential for evaluation as a prophylactic agent against COVID-19.

Designing a Mucoadhesive ChemoPatch to Ablate Oral Dysplasia for Cancer Prevention.

Oral cancer has a high mortality rate, and its treatment often causes debilitating complications. More than 90% of oral cancers are oral squamous cell carcinomas (OSCCs) that may develop from clinically recognizable oral premalignant lesions (OPLs). To eradicate OPLs before they turn into cancers, a non-invasive topical formulation is developed based on a novel combination of synergistically acting oxaliplatin (OXP) and mycophenolate (MPS) embedded in a controlled-release mucoadhesive patch fabricated by computer-aided 3D printing. After multiple rounds of testing and optimization, a v6.4 ChemoPatch is designed, which shows sustained release of OXP and MPS in vitro, minimal side leakage of drugs, an average elastic modulus of 2.38MPa, and suitable drug stability at 4°C or below for up to 12 months. In vivo analyses show almost all patches adhere to the dorsal tongue surface for 4 hours, and display a sustained release of OXP and MPS to tongue tissue for 3-4 hours. When applied in the 4-nitroquinoline-1-oxide-induced OPL rat model, the OXP-MPS patch significantly ablates dysplastic lesions with no damage to normal epithelial cells and minimal systemic absorption and side effects. This study reports the design of a novel mucoadhesive ChemoPatch as a noninvasive therapy to treat OPLs.

Drug‐Loaded Mucoadhesive Patch with Active Delivery and Controlled Releasing Ability

Drug-Loaded Mucoadhesive Patch In article number 2100203, Sukho Park and co-workers demostrate a drug-loaded patch equipped in wireless capsule, which is delivered to the gastrointestinal tract rapidly and accurately by an external magnetic field. The patch has excellent mucoadhesive properties even in a wet gastrointestinal environment. Since magnetic nanoparticles and doxorubicin are also loaded in the patch, it generates heat under an external alternating magnetic field and treats cancer cells through hyperthermia and drug release promotion.

Nano-emulsion of mangosteen rind extract in a mucoadhesive patch for periodontitis regenerative treatment: An in vivo study

ObjectiveTo investigate the therapeutic potential of nano-emulsion of mangosteen rind extract in a mucoadhesive gingival patch on periodontitis, and its effect on tumor necrosis factor alpha (TNF-α), receptor activator of nuclear factor kappa Β ligand (RANKL), and interleukin 10 (IL-10) expression. MethodsSixty Wistar rats were divided into four groups: positive control group (mucoadhesive patch with doxycycline), negative control group (mucoadhesive patch), treatment group I (mucoadhesive patch with mangosteen rind extract), and treatment group II (mucoadhesive patch with nano-emulsion of mangosteen rind extract). An experimental model of Porphyromonas gingivalis-induced periodontitis was established in rats by treatment with 0.03 mL bacteria locally (1 × 1010 colony-forming units) seven times at 2-day intervals in the gingival sulcus of mandibular anterior teeth. Treatment was 1 h/day for 3 days. On days 3, 5, and 7, five rats from each group were killed. TNF-α, IL-10, and RANKL expression was determined by dissecting the lower jaw for immunohistochemistry. ResultsThe mucoadhesive patch with nano-emulsion mangosteen rind extract significantly decreased TNF-α and RANKL expression and increased IL-10 expression (p < 0.05) compared to the treatment I, positive and negative control groups. ConclusionA mucoadhesive gingival patch with nano-emulsion of mangosteen rind extract has the potential to treat periodontitis by decreasing TNF-α, RANKL, and increasing IL-10 expression.

Drug‐Loaded Mucoadhesive Patch with Active Delivery and Controlled Releasing Ability

Herein, a mucoadhesive patch for gastrointestinal tracts with active delivery, hyperthermia, and controlled drug release function using a magnetically actuated capsule is proposed to overcome the drug delivery and efficiency challenges of wireless structures. The proposed patch has excellent adhesion to the gastrointestinal tract and contains anticancer drug doxorubicin and magnetic nanoparticles. This enables hyperthermia and the controlled release of the loaded drug under an alternating magnetic field (AMF). In addition, it can be delivered to multiple intestinal target lesions using a magnetically actuated capsule. Characteristic analyses of the proposed patch are performed, such as morphology, adhesion force measurement with intestine, temperature change under an AMF, and drug release. The feasibility of the patch delivery into the gastrointestinal tract is verified through locomotion performance tests and ex vivo patch delivery experiments using a magnetically actuated capsule. Finally, through an in vitro therapeutic effect test, the death of tumor cells using the proposed patch is confirmed. As a result, the possibility that the multiple mucoadhesive patches can be delivered to target lesions in a digestive tract through a magnetically actuated capsule and can treat the lesions through hyperthermia and active drug release using an AMF stimulation is verified.

Current Trends and Controversies in Periodontal Dressing – A Narrative Review

Periodontal dressings have a history of nine decades and yet, the uses and benefits of periodontal dressings are questioned. There are different types of periodontal dressings based on the composition, setting, consistency, and solubility. Various authors have studied the properties of periodontal dressings. However, majority of them have emphasized only on their biocompatibility and therapeutic benefits. Eugenol-based periodontal dressings are no longer used due to their cytotoxic properties. Currently, popular ones are zinc oxide-based without eugenol in their composition. Although light-cured periodontal dressings fetched some attention due to its biocompatibility, aesthetics and comfort in application, its use is limited due to relatively higher cost. Mucoadhesive patches were introduced, however, due to their limited action time, it is not indicated universally. In recent times, there is growing interest in biological dressing materials which are found to be more tissue friendly and aid in better healing. Literature reveals mixed opinions on the use of periodontal dressings in different clinical scenarios. As there is no proper consensus on the use of periodontal dressings, it becomes the choice of a clinician to decide on the use of periodontal dressing based on the clinical condition.

Polymeric and electrospun patches for drug delivery through buccal route: Formulation and biointerface evaluation

IntroductionOf the various transmucosal routes which are being considered for extended and controlled drug delivery, buccal route is superior to other methods owing to high administrability and milder environment for drug absorption. In this direction, mucoadhesive buccal films of venlafaxine were fabricated using a combination of biocompatible polymers. AimThe main objective of the study was to standardize an optimized formulation of polyvinyl alcohol, sodium carboxymethyl cellulose and sodium alginate that would lead to sustained drug delivery in the form of buccal patches. MethodsVarying polymeric concentrations were utilized for the fabrication of buccal patches via solvent casting method. The physical parameters were evaluated, followed by in vitro drug release studies. The electrospun nanofibers were prepared for optimized formulations and the buccal delivery system was compared to oral and intravenous routes for absorption, distribution, and elimination during in vivo studies using venlaflaxine. ResultsThe patches had high tensile strength with uniform drug content and surface pH in the range of 6.28–6.88. The release of drug was steady witha maximum release of 89.97% at 5 h. The negative hemolytic and cytotoxicity studies with TR146 cells over a range of concentrations indicated biocompatibility of the mucoadhesive patch with human tissues. The pharmacokinetics of the buccal patch of the radiolabeled drug, 99mTc-venlaflaxine, displayed favorable release pattern. The radiolabeled patch attached to rabbit buccal mucosa displayed high retention with controlled drug release as indicated by the Cmax and T1/2 values (19.94 ng/ml and 3 h). The drug release mechanism corresponded to a pure fickian diffusion-controlled mechanism following Higuchi's model. Electrospun fibrous patch of the drug had a 10% higher drug release than solvent cast patch. ConclusionIn vitro and in vivo data indicate that the polymeric system was successfully optimized for sustained drug release for about 5 h in a continuous manner with electrospun fibrous patch showing 10% increase in drug release studies. The patches displayed ideal physical and biocompatibility characteristics. This polymeric combination can therefore be further utilized for development of novel drug delivery systems with sustained drug release pattern.

Design and In-Vivo Evaluation of Risperidone Buccal Mucoadhesive Patches of Interpolymer Matrix

The buccal cavity is an alternate route for the administration of the drug. This route gained acceptance as increase in bioavailability is observed due to bypass of first pass metabolism. Solvent casting method was employed for the preparation of the risperidone mucoadhesive patches using different combinations of water soluble and water insoluble polymers using polyvinyl alcohol as a backing layer. Our main objective of this study was to understand the behaviour of water soluble and water insoluble polymers in combination on release pattern. Six different formulations of mucoadhesive patches were evaluated for physicochemical parameters like weight uniformity, content uniformity, thickness uniformity, surface pH, swelling studies, tensile strength, folding endurance, in-vitro drug release, and in-vivo drug absorption. Drug loaded mucoadhesive patches of various polymer bases had shown 35.64 to 72.33% drug release in 30 min in phosphate buffer solution of pH 6.6. In-vitro release data from patches were fit to different equations and kinetic models to explain release profiles. Kinetic models like Hixon-Crowell and Higuchi models were used. The formulation containing HPMC (15Cps) and polyvinyl pyrrolidone was considered as optimized based on the physicochemical and pharmaceutical properties. In-vivo studies in rabbits, carried out with prior permission from IAEC, showed 80.40% of drug release from the optimized patches. In-vivo and in-vitro correlations were found to be good. The drug absorption was found significant from the optimized formulation in healthy rabbits. The structure of the buccal membrane and permeability factors are similar in both human beings and rabbits. Therefore mucoadhesive patches of risperidone may be accepted with the important advantage of reduced risperidone dose.

Formulation Development, Evaluation, and Optimization of Mucoadhesive Patches of Venlafaxine Hydrochloride for Buccal Delivery

Formulation Development, Evaluation, and Optimization of Mucoadhesive Patches of Venlafaxine Hydrochloride for Buccal Delivery

A study of the mucoadhesive patches loaded with mangosteen peel extract in periodontitis

ObjectiveThe treatment of periodontitis with scaling and root planing has a good prognosis. However, periodontitis may also exacerbate. The mucoadhesive patch is one of the distribution systems of topical drugs, which is not irritable to the mucosa and eventually increases permeability. Based on phytochemical screening, mangosteen peel extract has an active ingredient with high anti-inflammatory and antibacterial properties. This study aims to understand the potential of a mucoadhesive patch loaded with mangosteen peel extract to inhibit alveolar bone damage in periodontitis. MethodsThis experimental laboratory research was conducted using 27 Wistar rats divided into three groups: the positive control group (0.7% tetracycline gel application), negative control group (mucoadhesive patch application), and experimental group (mucoadhesive patch loaded with mangosteen peel extract application). Rats were administered 1 × 109 colony-forming unit as much as 200 μL of Actinobacillus actinomycetemcomitans bacteria three times at 2-day intervals. Tetracycline gel and mucoadhesive patch application were administered for 1 h/day for 3 days. Three rats from each group were sacrificed on days 3, 5, and 7 after the application. The lower jaw was dissected for histopathological examination using haematoxylin and eosin staining to determine the number of osteoclasts and osteoblasts. ResultsThe mucoadhesive patches loaded with mangosteen peel extract significantly reduced the number of osteoclasts and increased the number of osteoblasts in all groups (p < 0.05). ConclusionThe mucoadhesive patches loaded with mangosteen peel extract can prevent alveolar bone damage in periodontitis by inhibiting the number of osteoclasts and increasing the number of osteoblasts.

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.

SOLID DISPERSION OF NEBIVOLOL HYDROCHLORIDE IMPREGNATED BUCCAL PATCH: FORMULATION AND CHARACTERIZATION

Objective: The objective of the present investigation was to design and characterize a mucoadhesive buccal patch of Nebivolol hydrochloride in order to administer a small dose of a drug to treat hypertension effectively and thereby avoiding disadvantages such as patient noncompliance and low bioavailability.&#x0D; Methods: The buccal patches were prepared by solvent casting method. The polymers used to formulate patches were HPMC K 15 M, PVP K 30, and propylene glycol was used as plasticizer and ethanol as the solvent. The drug-polymer compatibility studied was conducted by FTIR.&#x0D; Results: All the developed Patches had good transparency and stability. All formulated patches showed pH in the range of 6.49 to 7.22, and drug content was more than 90%. The folding endurance value showed that the patches are flexible and non-brittle. The in vitro residence time was found to more than 30 min. Thickness, % moisture absorption, and % moisture loss values were in a normal range. The drug release study was conducted for 8 h, and it was found drug release was decreased with the increase in polymer concentration. The in vitro release profiles of the drug from all the formulations appeared to follow Korsmeyer Peppa's exponential model, and release exponent (n) was found to be more than 0.45 so that the release can be characterized by Non–Fickian (anomalous) diffusion.&#x0D; Conclusion: From the results, it was concluded that drug released from formulated buccal patches follows sustained release pattern, Hence can be used for the treatment of the hypertensive patient.

Potential Therapy from Punica granatum Peel Extract for the Treatment of Recurrent Aphthous Stomatitis. Design, Formulation and Characterisation of a Mucoadhesive Patch

Recurrent aphthous stomatitis (RAS) is an inflammation that occurs in oral mucosa. Etiology of RAS maybe caused by several factors involving systemic conditions, local, microbes (Candida albicans), moniliasis,hygiene and genetics. Several studies has shown that pomegranate (Punica granatum L.) peel serves toinhibit Candida albicans, antibacterial Staphylococcus aureus, Staphylococcus mutans, Escherichia coli andantifungal Aspergillus niger, which is common microorganisms involved in dental and oral problems. Thisstudy aims to formulate a pomegranate peel extracts (PPE) mucoadhesive patch and test its effectiveness inhealing sores. PPE obtained from the maceration method. Polyvinylpyrrolidone patch formulations, chitosanand Hydroxypropyl Methyl Cellulose (HPMC) using a ratio of 1:1, 2:1, and 3:1 weight/volume. Patch testedhis physical characteristics, including weight uniformity, uniformity of dimension, thickness, surface pH,swelling and adhesion test, and in vivo test. The F8 formulation of PPE 10% with the addition of HPMC,tween, and glycerin have a fairly elastic properties. Even though experiment of physical evaluation produceuniformity of same weights and dimensions, pH 6.63, an average of swelling percentage 40.69% ± 16.37%and an average of stickness 13.50 ± 11.6 seconds. In vivo test show that formulation of PPE 10% has thesame effectivity in reducing the diameter of the mouth ulcers with the positive control group.

Sublingual protein delivery by a mucoadhesive patch made of natural polymers

The sublingual mucosa is an appealing route for drug administration. However, in the context of increased use of therapeutic proteins, development of protein delivery systems that will protect the protein bioactivity is needed. As proteins are fragile and complex molecules, current sublingual formulations of proteins are in liquid dosage. Yet, protein dilution and short residence time at the sublingual mucosa are the main barriers for the control of the dose that is delivered. In this work, a simple delivery scaffold based on the assembly of two polysaccharides, chitosan and hyaluronic acid, is presented. The natural polymers were assembled by the Layer-by-Layer methodology to produce a mucoadhesive and oro-dispersible freestanding membrane, shown to be innocuous for epithelial human cells. The functionalization of the membrane with proteins led to the production of a bioactive patch with efficient loading and release of proteins, and suitable mechanical properties for manipulation. Sublingual administration of the patch in mouse evidenced the absence of inflammation and an extended time of contact between the model protein ovalbumin and the mucosa compared to liquid formulation. The delivery of fluorescent ovalbumin in mouse sublingual mucosa demonstrated the penetration of the protein in the epithelium 10 min after the patch administration. Moreover, a migration assay with a chemokine incorporated into the patch showed no decrease in bioactivity of the loaded protein after enzymatic release. This study therefore provides a promising strategy to develop a sublingual protein delivery system. Statement of significanceAlthough the oral route is largely used for drug delivery, it has limitations for the delivery of proteins that can be degraded by pH or gastric enzymes. The sublingual route therefore appears as an interesting approach for protein administration. In this work, a simple delivery scaffold is presented based on the assembly of two polysaccharides by the Layer-by-Layer methodology to produce a mucoadhesive patch. The produced patch allowed efficient loading and release of proteins, as well as protection of their bioactivity. An extended time of contact between the protein and the mucosa compared to liquid formulation was highlighted in mouse model. This study provides a promising strategy to develop a sublingual protein delivery system.