Mucoadhesive Systems Research Articles

Carvacrol incorporation into novel controlled-release mucoadhesive systems for oral polymicrobial biofilm control

Carvacrol incorporation into novel controlled-release mucoadhesive systems for oral polymicrobial biofilm control

Substantive Dimethicone-Based Mucoadhesive Coatings

It is challenging to deliver therapeutics in the oral environment due to the wet surfaces, the nature of the mucosa and the potential for saliva washout. In this study, the development of a mucoadhesive dimethicone-based oral carrier system for adhesion to the hard tissue and mucosa in the mouth was examined. This study reports the viscosity and mucoadhesion of dimethicone based polymer blends. The viscosity of the materials was measured using a rheometer. The mucoadhesion of these materials was determined as the work of adhesion and peak tack force using the tensile test method with a texture analyzer. Materials were prepared with either calcium and phosphate salts or sodium fluoride as potential therapeutics for promoting remineralization and treating dentin hypersensitivity by mechanical occlusion. Scanning electron microscopy was used to look at mineral deposition on the surface of dental hard tissue after the application of the dimethicone-based formulations. The results of this study confirm the potential for using these dimethicone-based materials as mucoadhesive therapeutic delivery systems in the oral environment.

Role of Natural Polymers in Novel Drug Delivery Systems

Natural polymers have gained significant attention in the field of drug delivery due to their inherent biocompatibility, biodegradability, and low toxicity. This review article aims to provide a comprehensive overview of the diverse roles that natural polymers play in the development of novel drug delivery systems. Beginning with a classification of natural polymers based on their origin (plant, animal, microbial), we explore their unique characteristics and advantages over synthetic counterparts. The review discusses the pivotal role of natural polymers in formulating various drug delivery systems, including sustained/controlled release formulations, targeted delivery platforms, mucoadhesive systems, and nanotechnology-based approaches. Techniques such as emulsification, ionotropic gelation, coacervation, and electrospinning for natural polymer-based drug delivery are elucidated, highlighting their versatility and applicability across different administration routes. Furthermore, we delve into the diverse applications of natural polymers in drug delivery, encompassing oral, transdermal, ocular, injectable, nasal, buccal, and vaginal delivery routes. Recent advances and innovations in combining natural polymers with synthetic counterparts, incorporating stimuli-responsive properties, and personalized medicine approaches are also explored. Despite the numerous advantages offered by natural polymers, challenges such as variability in polymer properties, standardization issues, scale-up challenges, and regulatory considerations are discussed. The review concludes with future perspectives, highlighting emerging trends and opportunities for further research and development in the field of natural polymer-based drug delivery systems. Overall, this review provides valuable insights into the pivotal role of natural polymers in advancing drug delivery technology, paving the way for safer, more efficient, and patient-friendly therapeutic interventions.

Thiolated layered double hydroxide-based nanoparticles: A study on mucoadhesiveness and cytotoxicity

The aim of this study was the synthesis and characterization of thiolated Mg/Al Layered double hydroxide nanoparticles (nLDH) that can adhere to mucosal surfaces. For this purpose, initially, nLDH were synthesized and then their surface was modified with L-cysteine (Cys). Then the Cys-modified nanoparticle structure (nLDHCys) was characterized by FTIR, XRD and FE-SEM/EDS, and the amount of thiol groups was determined using the iodometric method. The cytotoxicity properties of nLDH and LDHCys were examined on cervical (HeLa), fibroblast (L929) and colon (HT29) cell lines. In addition, the adhesion of nanoparticles to mucosal surfaces has been evaluated through mucin interaction experiments and ex vivo tests on ewe vaginal tissue. The results from characterization studies prove that Cys molecule has been successfully modified on the surface of nLDH. Cytotoxicity studies demonstrated that Cys modification did not negatively affect the cell viability, and these results were extremely close to those of nLDH. Ex vivo tests on ewe vaginal tissue and mucin interaction demonstrated that nLDHCys enhanced retention on the mucosal surface. Considering their retention ability to mucosal surface and their biocompatible nature, nLDHCys is expected to play an important role as a promising option for a safe mucoadhesive nanoparticle system for biological applications in the future.

Mucoadhesive Itraconazole Nanocrystals With Precise Control of Surface Charge Incorporated to Chitosan Films for Buccal Drug Delivery

AbstractDrug delivery to mucosal tissues presents considerable challenges related to the complex nature of the mucus layer protecting such tissues. This aggravates when delivering hydrophobic drugs, often requiring incorporation of drugs to nanoparticles and use of mucoadhesive systems. This paper aimed to develop an antifungal chitosan (CHI)‐based film loading itraconazole (ITZ) nanocrystals (NCs) with precisely controlled surface charge for enhanced mucoadhesion. Cationic and anionic ITZ NCs are prepared using wet media milling with mean particle sizes and zeta potentials of 226.9 ± 1.4 nm and 234.0 ± 2.90 nm, and +15.4 ± 2.8 mV and −16.2 ± 1.3 mV, for the cationic and anionic NCs, respectively. Cationic ITZ‐NCs exhibits a higher affinity to mucin particles. NCs‐loaded films showed stronger mechanical properties and adhesiveness compared with ITZ powder‐loaded films. Physicochemical analysis reveals that crystalline properties of the ITZ are preserved, with no drug‐excipients interaction. A significantly higher amount of ITZ mucosal deposition is obtained from films containing NCs (1360.23 ± 718.73 µg cm−2) compared with that from films containing ITZ powder (58.83 ± 37.45 µg cm−2). This work demonstrates the feasibility of tailoring the NCs surface, with the resultant systems showing potential for the management of fungal infections in mucosal tissues.

Mucoadhesive and drug release of cholic acid based thiomeric micelles and encapsulated silver and gold nanoparticles for anticancer studies

Among the various drug delivery system, mucoadhesive formulation is a promising approach to deliver drugs and vaccine through close contact with the absorption site and mucous membrane. Bile acids have received considerable interest in drug delivery (DD) applications owing to their advantages of biocompatibility, ability to act as both drug solubilizing and permeation-modifying agents. In this aspects, cholic acid (CA) based thiomeric micelles with improved mucoadhesive properties have been synthesized by functionalization of thiol groups and conjugation of PEG. The synthesized CA based thiomeric micelles (TCA-PEG) were characterized by 1HNMR, ATR-IR, GPC, Zeta potential and contact angle techniques. The critical micelle concentration (CMC) of TCA-PEG was measured by a fluorescence spectrometer using pyrene as a probe. The mucoadhesive properties of TCA-PEG polymeric micelles (PMs) were examined on the goat anterior tongue mucosa with an effectively higher adhesion of 40 % up to 3 h study period. Also, curcumin loaded TCA-PEG PMs showed only 13 % of the drug released up to the period of 3 h. The TCA-PEG PMs act as reducing and stabilizing agents for the preparation of gold and silver nanoparticle (Ag and Au NPs) and were characterized by UV–visible, DLS, Zeta potential, XPS, and HR-TEM techniques. The cytotoxicity and cellular apoptosis of TCA-PEG PMs encapsulated Ag and Au NPs were examined by MTT assay and AO/PI dual staining using MCF-7 breast cancer cells wherein AgNPs showed an effective cytotoxicity than AuNPs. The developed TCA-PEG PMs act as reservoir for soubilization of hydrophobic and hydrophilic drugs and ideal template for encapsulation of silver and gold nanoparticles for mucoadhesive DD system.

Formulation and evaluation of amoxapine mucoadhesive buccal films

Among innovative drug delivery methods, buccal mucoadhesive systems have been attracting much interest recently because of their capacity to stick to the oral mucosa, stay there, and gradually release their drug content. By improving medication absorption through the oral mucosa and reducing the hepatic first-pass impact, buccal mucoadhesive films can increase the drug's bioavailability and enhance its therapeutic effect. The current study aimed to synthesize the medicine as a buccal bioadhesive film, which reduces the frequency of dosage form administration by releasing the drug at a sufficient concentration over time. Because this formulation is simple to administer and requires no water to swallow, improved patient compliance is one of its benefits. Dissolving profile as investigated in USP dissolving apparatus type 1 using saliva at pH 6.8. The impact of factors such as polymer type, concentration, and release profile of Amoxapine was investigated. The formulation was optimized Based on several evaluation criteria, including drug content and in-vitro drug release. Formulation F6 successfully releases the drug in 7 hours. The stability studies followed ICH recommendations, and the results showed that the optimized formulation was stable. The IR spectra demonstrated the stable qualities of Amoxapine in a mixture of polymers utilized and revealed the absence of interaction between the drug and the selected polymer.

Recent Updates on Nanocarriers for Drug Delivery in Posterior Segment Diseases with Emphasis on Diabetic Retinopathy.

In recent years, various conventional formulations have been used for the treatment and/or management of ocular medical conditions. Diabetic retinopathy, a microvascular disease of the retina, remains the leading cause of visual disability in patients with diabetes. Currently, for treating diabetic retinopathy, only intraocular, intravitreal, periocular injections, and laser photocoagulation are widely used. Frequent administration of these drugs by injections may lead to serious complications, including retinal detachment and endophthalmitis. Although conventional ophthalmic formulations like eye drops, ointments, and suspensions are available globally, these formulations fail to achieve optimum drug therapeutic profile due to immediate nasolacrimal drainage, rapid tearing, and systemic tearing toxicity of the drugs. To achieve better therapeutic outcomes with prolonged release of the therapeutic agents, nano-drug delivery materials have been investigated. These nanocarriers include nanoparticles, solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), dendrimers, nanofibers, in-situ gel, vesicular carriers, niosomes, and mucoadhesive systems, among others. The nanocarriers carry the potential benefits of site-specific delivery and controlled and sustained drug release profile. In the present article, various nanomaterials explored for treating diabetic retinopathy are reviewed.

Expanding the Manufacturing Approaches for Gastroretentive Drug Delivery Systems with 3D Printing Technology.

Gastroretentive drug delivery systems (GRDDSs) have gained substantial attention in the last 20 years due to their ability to retain the drug in the stomach for an extended time, thus promoting an extended release and high bioavailability for a broad range of active pharmaceutical ingredients (APIs) that are pH-sensitive and/or have a narrow absorption window. The currently existing GRDDSs include floating, expanding, mucoadhesive, magnetic, raft-forming, ion-exchanging, and high-density systems. Although there are seven types of systems, the main focus is on floating, expanding, and mucoadhesive systems produced by various techniques, 3D printing being one of the most revolutionary and currently studied ones. This review assesses the newest production technologies and briefly describes the in vitro and in vivo evaluation methods, with the aim of providing a better overall understanding of GRDDSs as a novel emerging strategy for targeted drug delivery.

Self-assembly mucoadhesive beads of κ-carrageenan/sericin for indomethacin oral extended release

Oral drug administration, especially when composed of mucoadhesive delivery systems, has been a research trend due to increased residence time and contact with the mucosa, potentially increasing drug bioavailability and stability. In this context, this study aimed to develop self-assembly mucoadhesive beads composed of blends of κ-carrageenan and sericin (κ-Car/Ser) loaded with the anti-inflammatory drug indomethacin (IND). We investigated the swelling, adhesion behaviour, and mechanical/physical properties of the beads, assessing their effects on cell viability, safety and permeation characteristics in both 2D and triple-culture model. The swelling ratio of the beads indicated pH-responsiveness, with maximum water absorption at pH 6.8, and strong mucoadhesion, increasing primarily with higher polymer concentrations. The beads exhibited thermal stability and no chemical interaction with IND, showing improved mechanical properties. Furthermore, the beads remained stable during accelerated and long-term storage studies. The beads were found to be biocompatible, and IND encapsulation improved cell viability (>70 % in both models, 79 % in VN) and modified IND permeation through the models (6.3 % for F5 formulation (κ-Car 0.90 % w/v | Ser 1.2 % w/v| IND 3.0 g); 10.9 % for free IND, p < 0.05). Accordingly, κ-Car/Ser/IND beads were demonstrated to be a promising IND drug carrier to improve oral administration while mitigating the side effects of non-steroidal anti-inflammatories.

A recent update on gastro retentive drug delivery systems

Gastro retentive drug delivery systems (GRDDS) have garnered significant attention in recent years due to their potential to enhance therapeutic efficacy and patient compliance by prolonging gastric residence time and optimizing drug release kinetics. This review provides a comprehensive overview of the latest advancements in GRDDS, focusing on formulation strategies, design principles, and evaluation methodologies. Various approaches such as floating systems, mucoadhesive systems, expandable systems, and magnetic systems are discussed in detail, highlighting their mechanisms of action and applications in targeted drug delivery. Furthermore, recent innovations in materials science and formulation technologies have enabled the development of novel GRDDS with improved biocompatibility, stability, and controlled release profiles. The review also addresses challenges associated with GRDDS, including physiological variability, drug stability, and regulatory considerations, and proposes potential strategies to overcome these obstacles. Additionally, the clinical relevance of GRDDS in the treatment of various gastrointestinal disorders and their future prospects in personalized medicine and targeted therapy are explored. Overall, this review aims to provide valuable insights into the current state-of-the-art in GRDDS research and its implications for the advancement of drug delivery science.

Development of mucoadhesive microspheres for intranasal delivery of fluconazole as an alternative treatment of cryptococcal meningitis infection in patients with acquired immunodeficiency

Cryptococcal meningitis is a deadly disease with few treatment options. Its incidence is still high and closely linked to the HIV/AIDS epidemic. This study aimed to develop a mucoadhesive microsphere delivery system for fluconazole for the intranasal route. Microspheres of mucoadhesive fluconazole formulation variables such as different amounts of drug concentration and polymer concentration were prepared by a simple emulsion-crosslinking method.The prepared microspheres' surface was characterised by SEM (Scanning electron microscopy) and evaluated for particle size, entrapment efficiency, production yield, infrared spectroscopic study, in-vitro muco-adhesion, and in-vitro drug release. The results showed that formula 1 is the optimal mucoadhesive microsphere preparation, with a particle size of 56.375m, a spherical surface shape, an entrapment efficiency of 99.96%, and a greater mucoadhesive capability during 6-hour evaluation. Furthermore, wash-off examination revealed that the mucoadhesive ability of this delivery system has a long duration and may release the active material at the right time. The result of the researches suggesting that the formulation of mucoadhesive microspheres of fluconazole could be used to treat cryptococcal meningitis infection in HIV/AIDS patients.

Analyzing the interactions and miscibility of silk fibroin/mucin blends

AbstractMucin, a glycoprotein with viscoelastic properties, and silk fibroin, a protein excreted from silkworms with properties of thermal and mechanical resistance, have been probed as building blocks in the design of biomaterials. Aiming to evaluate the interaction and miscibility between mucin and fibroin, we synthesized silk fibroin and mucin (SF/MU) blends for biomedical applications. The morphological analysis of the SF/MU blends showed the presence of two phases, suggesting a partial miscibility between the polymers. The degradation temperature of the SF/MU blends increased with an increase in the silk fibroin content, indicating that silk fibroin contributed to the thermal stability of the blends. The glass transition temperature of the SF/MU blends lay between the values of the pure polymers. The Fourier‐transform infrared spectroscopy results pointed out that the interaction between fibroin and mucin occurred between the amine group of silk fibroin and mucin carboxyl and hydroxyl groups. The outcomes of this work provided essential information on the miscibility of the SF/MU blends. These findings will be critical for further studies with fibroin and mucin‐based biomaterials, especially in mucoadhesive systems and wound healing applications.

Nanoparticles of Thiolated Xanthan Gum for the Oral Delivery of Miconazole Nitrate: In Vitro and In Vivo Evaluation.

The objective of this research was to develop a mucoadhesive delivery system that improves permeation for the administration of poorly absorbed oral medications. Thiolation of xanthan gum (XGM) was carried out by esterification with mercaptobutyric acid. Fourier-transformed infrared spectroscopy was used to confirm thiol-derivatization. Using Ellman's technique, it was revealed that the xanthan-mercaptobutyric acid conjugate had 4.7 mM of thiol groups in 2 mg/mL of polymeric solution. Using mucosa of sheep intestine, the mucoadhesive properties of XGM and thiolated xanthan gum (TXGM) nanoparticles were investigated and we found that TXGM had a longer bioadhesion time than XGM. The disulfide link that forms between mucus and thiolated XGM explains why it has better mucoadhesive properties than XGM. A study on in vitro miconazole (MCZ) release using phosphate buffer (pH 6.8) found that TXGM nanoparticles released MCZ more steadily than MCZ dispersion did. A 1-fold increase in the permeation of MCZ was observed from nanoparticles using albino rat intestine compared to MCZ. Albino rats were used to test the pharmacokinetics of MCZ, and the results showed a 4.5-fold increase in bioavailability. In conclusion, the thiolation of XGM enhances its bioavailability, controlled release of MCZ for a long period of time, and mucoadhesive activity.

An antifouling supramolecular polymer ophthalmic ointment alleviates symblepharon in rat alkali burn eyes.

Symblepharon is an adverse ocular disease resulting in ocular discomfort and impaired vision, severely dragging down a patient's quality of life. Due to the specificity of the ocular surface, the retention time of drugs on it is short, leading to limited therapeutic effects for ocular diseases. Therefore, it is imperative to design a novel drug delivery system, which can not only prolong the retention time of a drug but also play an anti-fibrosis role in symblepharon. Herein, an antifouling supramolecular polymer ophthalmic ointment consisting of poly(N-acryloyl alaninamide) (PNAAA), vitamin C (VitC) and levofloxacin (Levo) was developed (termed PNAVL ophthalmic ointment), which acted as a mucoadhesive and long-acting ocular delivery system. This antifouling PNAVL ophthalmic ointment improved the retention time of VitC and Levo, and simultaneously provided anti-inflammation and anti-fibrosis effects for mitigating symblepharon after ocular alkali burn injury.

Chitosan as floating-mucoadhesive polymers in gastroretentive drug delivery

Oral drug delivery is limited by incomplete absorption in the digestive tract. The absorption of oral drugs in the stomach is affected by several factors, including gastric residence time, which causes the drug to be unable to be retained in the stomach for a long time, causing suboptimal drug absorption. One of the drug delivery systems that can prolong contact duration within the stomach is gastroretentive drug delivery system (GRDDS). GRDDS has various advantages, notably in improving the bioavailability of drugs. Several systems are involved in the GRDDS, including the floating and mucoadhesive systems. The floating system makes the drug float so it can be retained longer in the stomach. There are two mechanisms in the floating system: the effervescent and non-effervescent mechanisms. The mucoadhesive system works by adhering to the mucus or epithelial cells of the stomach. The mechanisms of mucoadhesive systems involves two stages: the contact and consolidation stages. The combination of the floating and mucoadhesive systems is aimed to improve the efficiency and effectiveness of a preparation for prolonged retention in the stomach. The choice of polymer is one of the crucial factors affecting this system. Chitosan is a natural polymer that has been evaluated for its potential in a gastroretentive floating beads delivery system. It has various advantageous properties, such as non-toxicity, biocompatibility, and biodegradability.

Development of thiolated xanthan gum-stearylamine conjugate based mucoadhesive system for the delivery of biochanin-A to melanoma cells

Recently, instead of creating new active compounds, scientists have been working to increase the bioavailability and residence time of existing drugs by modifying the characteristics of the delivery systems. In the present study, a novel mucoadhesive bioconjugate (SN-XG-SH) was synthesized by functionalizing a polysaccharide xanthan gum (XG) with cysteamine hydrochloride (CYS) and a lipid stearylamine (SN). FTIR, CHNS and 1H NMR studies confirmed the successful synthesis of SN-XG-SH. Mucoadhesion of the thiolated XG was enhanced and evaluated by different methods. Disulfide bond formation between thiolated XG and skin mucus enhances mucoadhesive behavior. The mucoadhesive bioconjugate was used to prepare nanoparticles for the delivery of hydrophobic biochanin-A (Bio-A) for the treatment of melanoma. The thiolated xanthan gum nanoparticles also demonstrated high drug entrapment efficiency, sustained drug release, and high storage stability. The drug loaded nanoparticles (Bio-A@TXNPs) significantly improved the cytotoxicity of Bio-A against human epidermoid cancer cells (A431 cells) by inducing apoptosis and changing mitochondrial membrane potential. In conclusion, thiolation of XG improves its mucoadhesive properties and prolongs the release of Bio-A. Thus, thiolated XG conjugate has a high potential for use as a bioadhesive agent in controlled and localised delivery of drugs in different skin diseases including melanoma.

Metronidazole loaded chitosan–phytic acid polyelectrolyte complex nanoparticles as mucoadhesive vaginal delivery system for bacterial vaginosis

Bacterial vaginosis (BV) is a recurring infection that is difficult to treat due to the limited bioavailability of antimicrobials. In this study, Metronidazole (MTZ)-loaded chitosan nanoparticles (MCSNP) were synthesized employing phytic acid (PA) as a crosslinking agent for treating bacterial vaginosis. The prepared MCSNPs were characterized for size, shape, surface charge, compatibility, cytotoxicity, biofilm inhibition, and in-vitro/in-vivo antimicrobial activities. Morphological examination revealed that nanoparticles generated from 0.535 % w/v chitosan and 0.112 % w/v PA were non-spherical, discontinuous, and irregular, with zeta potential ranging from 25.00 ± 0.45 to 39 ± 0.7. The results of DSC and XRD demonstrated no change in the physical state of the drug in the finished formulation. The optimized formulation demonstrates a cumulative drug release of about 98 ± 1.5 % within 8 h. Antimicrobial studies demonstrated that the optimized formulation had enhanced efficacy against acid-adapted BV pathogens, with a MIC value of 0.9 ± 0.1 μg/mL. Compared to the MTZ alone, the in-vivo antibacterial results of in the case of developed nanoparticles showed a four-fold reduction in bacterial count in female Swiss albino mice. Based on the experimental findings, it was concluded that MCSNPs, due to their excellent physiochemical and antibacterial properties, could serve as a potential topical alternative for treating BV.

Crosslinked chitosan microparticles as a safe and efficient DNA carrier for intranasal vaccination against cutaneous leishmaniasis

Intranasal (i.n.) vaccination with adjuvant-free plasmid DNA encoding the leishmanial antigen LACK (LACK DNA) has shown to induce protective immunity against both cutaneous and visceral leishmaniasis in rodents. In the present work, we sought to evaluate the safety and effectiveness of d,l-glyceraldehyde cross-linked chitosan microparticles (CCM) as a LACK DNA non-intumescent mucoadhesive delivery system. CCM with 5 μm of diameter was prepared and adsorbed with a maximum of 2.4 % (w/w) of DNA with no volume alteration. Histological analysis of mouse nostrils instilled with LACK DNA / CCM showed microparticles to be not only mucoadherent but also mucopenetrant, inducing no local inflammation. Systemic safeness was confirmed by the observation that two nasal instillations one week apart did not alter the numbers of bronchoalveolar cells or blood eosinophils; did not alter ALT, AST and creatinine serum levels; and did not induce cutaneous hypersensitivity. When challenged in the footpad with Leishmania amazonensis, mice developed significantly lower parasite loads as compared with animals given naked LACK DNA or CCM alone. That was accompanied by increased stimulation of Th1-biased responses, as seen by the higher T-bet / GATA-3 ratio and IFN-γ levels. Together, these results demonstrate that CCM is a safe and effective mucopenetrating carrier that can increase the efficacy of i.n. LACK DNA vaccination against cutaneous leishmaniasis.

Carbomer and ethyl cellulose optimisation in the preparation of mucoadhesive microspheres ciprofloxacin hydrochloride

Background: Ciprofloxacin hydrochloride (CH) is an antibiotic used to treat urinary tract infections. CH has a short half-life and low bioavailability. Microspheres combined with a mucoadhesive system can increase the residence time of the drug in the stomach to increase the bioavailability of CH. Objective: This research was conducted to obtain the best amount of carbomer as a polymer mucoadhesive and ethyl cellulose as a matrix polymer based on factorial design. Method: The factorial design 22 was used to determine the amount of carbomer and ethyl cellulose to produce optimum mucoadhesive microspheres. Three responses were observed in this study: particle size, entrapment efficiency, and mucoadhesive strength. Result: The resulting entrapment efficiency was 69.0%, particle size was 404.52 nm, and mucoadhesive strength was 64.3 grams, with drug loading and yield values of 19.13% and 99.8%, respectively. Conclusion: The optimum formula with the highest response value is the formula containing 300 mg carbomer and 1000 mg ethyl cellulose.