Chitosan-based mucoadhesive films loaded with curcumin for topical treatment of oral cancer.

This study aimed to develop mucoadhesive chitosan-based films capable of enhancing the curcumin penetration into the oral mucosa to treat oral cancers. We developed three films containing medium molecular weight chitosan (190-310 KDa) and other excipients (polyvinyl alcohol, Poloxamer®407, and propylene glycol) that have proven to be compatible with each other and with curcumin in thermal analyses. The films were smooth, flexible, and precipitates free, with uniform weight and thickness, pH compatible with the oral mucosa, resistance to traction, and entrapped curcumin in a high proportion. They also exhibited necessary swelling and mucoadhesion for tissue adherence. Ex vivo penetration studies proved that the films significantly increased the penetration of curcumin into the oral mucosa compared to control, even when the mucosa was subjected to a condition of simulated salivation. Curcumin exhibited cytotoxic activity in vitro in the two head and neck cancer cell lines (FaDu, SCC-9) at doses close to those found in penetration studies with the films. When combined with radiotherapy, curcumin demonstrated superiority over single doses of radiotherapy at 4, 8, and 12 Gy. Therefore, the developed films may represent a promising alternative for the topical treatment of oral tumors.

Bioadhesive and drug-loaded cellulose nanofiber/alginate film for healing oral mucosal wounds.

Recurrent oral ulcers are common oral mucosal lesions that severely reduce patients' quality of life. Commercial mucoadhesive films are easily disrupted due to oral movement and complex wet environments, thus reducing drug utilization and even causing toxic side effects. Herein, we report a mucoadhesive film composed of Ca2+-crosslinked carboxymethylated cellulose nanofibers and alginate, in which two drugs of dexamethasone (DXM) and dyclonine hydrochloride (DYC) are loaded for the treatment of oral ulcers. The wet films have a high Young's modulus of 7.1 ± 2.6 MPa and a large strain of 53.6 ± 9.8 % and adhere to tissue strongly, which allows them to resist the deformation caused by frequent oral movement. The films also have nice durability against water and excellent biocompatibility. Moreover, the drug release was controlled at different rates. The fast release of DYC facilitates the quick relief of pain, while the slow release of DXM benefits the long-term treatment of wounds. Finally, the animal experiment demonstrates the films displayed excellent therapeutic efficacy in healing oral ulcers.

Buccal Administration of a Zika Virus Vaccine Utilizing 3D-Printed Oral Dissolving Films in a Mouse Model.

Over the years, research regarding the Zika virus has been steadily increasing. Early immunization for ZIKV is a priority for preventing complications such as microencephaly and Guillain-Barré syndrome (GBS). Unlike traditional vaccination approaches, oral dissolving films (ODFs) or mucoadhesive film technology is an emerging, exciting concept that can be used in the field of pharmaceuticals for vaccine design and formulation development. This attractive and novel method can help patients who suffer from dysphagia as a complication of a disease or syndrome. In this study, we investigated a microparticulate Zika vaccine administered via the buccal route with the help of thin films or oral dissolving films (ODFs) with a prime dose and two booster doses two weeks apart. In vitro, the ODFs displayed excellent physiochemical properties, indicating that the films were good carriers for vaccine microparticles and biocompatible with the buccal mucosa. In vivo results revealed robust humoral (IgG, subtypes IgG1 and IgG2a) and T-cell responses (CD4+/CD8+) for ZIKV-specific immunity. Both the Zika MP vaccine and the adjuvanted Zika MP vaccine affected memory (CD45R/CD27) and intracellular cytokine (TNF-α and IL-6) expression. In this study, ZIKV vaccination via the buccal route with the aid of ODFs demonstrated great promise for the development of pain-free vaccines for infectious diseases.

Permeability of triamcinolone acetonide, released from mucoadhesive films, through a buccal mucosa-mimetic barrier: Permeapad™.

OBJECTIVES: The permeability of triamcinolone acetonide (TA), from bilayer mucoadhesive buccal films, through a biomimetic membrane, Permeapad™, was investigated employing Franz diffusion cell. The delivery systems composition and ethyl cellulose (EC) backing layer, on drug permeability, were assessed. METHODS: Three TA-loaded films were tested; hydroxypropyl methylcellulose (HPMC K4M; bilayer [F1] and monolayer), HPMC K4M/Polyvinylpyrrolidone (PVP): 90/10 [F2], and HPMC K15M film [F3]. All films contained propylene glycol (PG-plasticiser). TA solution alone was used as a control. TA permeability via a Permeapad™ barrier, simulating buccal mucosa, was assessed over 8 h using a Franz diffusion cell. TA permeated into the receptor compartment, released in the donor compartment, and located on/within the Permeapad™ barrier were analysed using UV-spectrophotometer. RESULTS: 45.7 % drug retention within the Permeapad™ barrier was delivered from F1 (highest). F1, F2, and F3 significantly improved the TA's permeability through Permeapad™, compared to TA solution alone (e.g., 8.5 % TA-solution, 21.5 %-F1), attributed to the synergy effect of HPMC and propylene glycol acting as penetration enhancers. F1 displayed a significant increase in drug permeability (receptor compartment; 21.5 %) compared to F3 (17.0 %). PVP significantly enhanced drug permeability (27.5 %). Impermeable EC backing layer controlled unidirectional drug release and reduced drug loss into the donor compartment (e.g., ∼28 % for monolayer film to ∼10 % for bilayer film, F1). SIGNIFICANCE: The mucoadhesive films demonstrated improved TA permeability via Permeapad™. The findings suggest that these bilayer mucoadhesive films, particularly F1, hold promise for the effective topical treatment of oral mucosa disorders, such as recurrent aphthous stomatitis and oral lichen planus.

Mucoadhesive film for oral delivery of vaccines for protection of the respiratory tract.

The delivery of vaccines plays a pivotal role in influencing the strength and longevity of the immune response and controlling reactogenicity. Mucosal immunization, as compared to parenteral vaccination, could offer greater protection against respiratory infections while being less invasive. While oral vaccination has been presumed less effective and believed to target mainly the gastrointestinal tract, trans-buccal delivery using mucoadhesive films (MAF) may allow targeted delivery to the mucosa. Here we present an effective strategy for mucosal delivery of several vaccine platforms incorporated in MAF, including DNA plasmids, viral vectors, and lipid nanoparticles incorporating mRNA (mRNA/LNP). The mRNA/LNP vaccine formulation targeting SARS-CoV-2 as a proof of concept remained stable within MAF consisting of slowly releasing water-soluble polymers and an impermeable backing layer, facilitating enhanced penetration into the oral mucosa. This formulation elicited antibody and cellular responses comparable to the intramuscular injection, but also induced the production of mucosal IgAs, highlighting its efficacy, particularly for use as a booster vaccine and the potential advantage for protection against respiratory infections. The MAF vaccine preparation demonstrates significant advantages, such as efficient delivery, stability, and simple noninvasive administration with the potential to alleviate vaccine hesitancy.