High-Payload Buccal Delivery System of Amorphous Curcumin–Chitosan Nanoparticle Complex in Hydroxypropyl Methylcellulose and Starch Films

Oral delivery of curcumin (CUR) has limited effectiveness due to CUR’s poor systemic bioavailability caused by its first-pass metabolism and low solubility. Buccal delivery of CUR nanoparticles can address the poor bioavailability issue by virtue of avoidance of first-pass metabolism and solubility enhancement afforded by CUR nanoparticles. Buccal film delivery of drug nanoparticles, nevertheless, has been limited to low drug payload. Herein, we evaluated the feasibilities of three mucoadhesive polysaccharides, i.e., hydroxypropyl methylcellulose (HPMC), starch, and hydroxypropyl starch as buccal films of amorphous CUR–chitosan nanoplex at high CUR payload. Both HPMC and starch films could accommodate high CUR payload without adverse effects on the films’ characteristics. Starch films exhibited far superior CUR release profiles at high CUR payload as the faster disintegration time of starch films lowered the precipitation propensity of the highly supersaturated CUR concentration generated by the nanoplex. Compared to unmodified starch, hydroxypropyl starch films exhibited superior CUR release, with sustained release of nearly 100% of the CUR payload in 4 h. Hydroxypropyl starch films also exhibited good payload uniformity, minimal weight/thickness variations, high folding endurance, and good long-term storage stability. The present results established hydroxypropyl starch as the suitable mucoadhesive polysaccharide for high-payload buccal film applications.

Cytokine-Related Effect of Buccal-Delivered Collagen Peptide Incorporated in Mucoadhesive Films to Improve Female Skin Conditions

Recently, interest in collagen products has increased in the industries However, collagen products that are taken orally have the problem of being degraded by digestive enzymes. Therefore, a collagen peptide buccal delivery film (C-BDF) was developed to enhance the absorption without destruction and a clinical trial was conducted. A C-BDF was developed as a double layer and the permeation of collagen peptide (CP) through swine mucosa was investigated. This clinical study was performed on 43 healthy women, who were divided into either a control (n = 21) or test group (n = 22), over the course of 4 weeks. Skin assessments analyzed the hydration, elasticity, and roughness. In addition, the production of peroxynitrite and IL-1α in RAW 264.7 cells in supernatant media was conducted. A total of 1 kDa of CP in BDF showed significantly stronger permeation through swine mucosa compared to 3 kDa of CP in BDF. The C-BDF significantly enhanced skin hydration, elasticity, and roughness, and it removed wrinkles with no side effects after 2 weeks of intake. In addition, the production of peroxynitrite and IL-1α after the treatment with CP was significantly increased. Therefore, this study showed that collagen peptides could be completely absorbed into mucosa via a buccal delivery system and homeopathic effects might occur.

Formulation Development And In Vitro-Ex Vivo Assessment Of Simvastatin Niosomal Buccal Films

Aim: Aim of the present study is to develop and characterize simvastatin niosomal film for effective buccal delivery. Methods: Simvastatin niosomes were developed by film hydration technique followed by high-pressure homogenization using chiller at 5°C. The simvastatin niosomes were characterized for various physicochemical parameters and simvastatin plain and niosomal films were prepared using PEO as the base by solvent casting technique. Results: From the simvastatin niosomes suspension, the percentage assay was found in the range of 96 to 103%, particles size was found in the range of 112nm to 308nm, the zeta potential was found in the range of -9 to -25.8mV, the %EE was found in the range of 28% to 91% and the in vitro permeation was found in the range of 43.41% to 98% respectively. The niosomal film shown superior results as compared to simvastatin plain film. The FTIR and DSC confirm the compatibility among the existed excipients. Conclusion: Niosomes alter the physicochemical properties of simvastatin by buccal route. The prolonged permeation (96.12% up to 24hrs) of simvastatin was observed from niosomes film across the porcine buccal cavity, due to the presence of CPE in the composition, which would be useful for effective buccal delivery.

A mussel-inspired film for adhesion to wet buccal tissue and efficient buccal drug delivery

Administration of drugs via the buccal route has attracted much attention in recent years. However, developing systems with satisfactory adhesion under wet conditions and adequate drug bioavailability still remains a challenge. Here, we propose a mussel-inspired mucoadhesive film. Ex vivo models show that this film can achieve strong adhesion to wet buccal tissues (up to 38.72 ± 10.94 kPa). We also demonstrate that the adhesion mechanism of this film relies on both physical association and covalent bonding between the film and mucus. Additionally, the film with incorporated polydopamine nanoparticles shows superior advantages for transport across the mucosal barrier, with improved drug bioavailability (~3.5-fold greater than observed with oral delivery) and therapeutic efficacy in oral mucositis models (~6.0-fold improvement in wound closure at day 5 compared with that observed with no treatment). We anticipate that this platform might aid the development of tissue adhesives and inspire the design of nanoparticle-based buccal delivery systems.

‘Preparation and characterization of a novel mucoadhesive carvedilol nano-sponge: a promising platform for buccal antihypertensive delivery’

Purpose: Carvedilol (CRV) is a non-selective beta-blocker used for hypertension treatment, angina pectoris, and heart failure. Oral administration of CRV showed poor bioavailability (25%), which may be due to exposure to the first-pass metabolism. Buccal delivery was used to boost its bioavailability.Methods: In this study carboxymethylcellulose/hydroxypropyl cellulose (CMC/HPC) composite buccal sponge enriched with CRV bilosomes was developed. Bilosomes were prepared using the thin-film hydration-sonication technique by applying a 32 -factorial design.Results: BL9 possessed the highest desirability value (0.861) and therefore, it was chosen as an optimal bilosomes. It exhibited a spherical shape with 217.2 nm, 87.13% entrapment efficiency, and a sustained release of CRV up to 24h. Consecutively, BL9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain a CMC-HPCL9 bilosomal sponge to enhance CRV buccal delivery. Morphological analysis of the prepared sponge with improved swelling showed a porosity of 67.58 percent. The in vivo assessment of rats indicates that the CMC-HPC/BL9 sponge enhances systolic/diastolic blood pressure, lipid profiles, oxidative stress biomarkers, and heart biomarkers with improved heart tissue quality.Conclusion: These results strongly encourage the use of this novel CMC-HPC/BL9 composite buccal sponge for the management of hypertension.

Interpolymer Complexes Based on Carbopol® and Poly(2-ethyl-2-oxazoline) as Carriers for Buccal Delivery of Metformin

Introduction. Buccal drug delivery has a number of advantages over oral administration: ease of application, good blood supply to the buccal mucosa, drug can enter the systemic circulation directly, avoiding the "first pass effect through the liver", and are not exposed to the acidic environment of the gastric juice and the destructive action of digestive enzymes. The use of interpolymer complexes (IPCs) makes it possible not only to ensure adhesion to the mucosal membranes of the oral cavity, but also to achieve a prolonged release of drugs.Aim. Development of carriers based on interpolymer complexes using Carbopol® 971 NF (C971) and poly(2-ethyl-2-oxazoline) (POZ) of different molecular weights for buccal delivery of metformin (MF).Materials and methods. The study of IPC adhesion was carried out using a TA.XTplus texture analyzer (Stable Micro Systems, UK); mucin compacts with a diameter of 13 mm were used as a substrate; these were prepared by compressing porcine gastric mucin powder using a manual hydraulic press for IR spectroscopy (PerkinElmer, USA) at a pressure of 2.45 MPa. The study of the swelling capacity was carried out by placing polymer matrices in an artificial saliva medium, with constant thermostating at a temperature of 37.0 ± 0.5 °C for 5 hours. The study of the release of MF from the matrices based on IPC was carried out using a DFZ II apparatus (Erweka, Germany) according to the Flow Through Cell method (USP IV) with cells for tablets (22.6 mm) and adaptors for ointments, creams and gels in a medium simulating saliva. The concentration of MF in the samples from the dissolution tests was determined with UV-spectrophotometry (Lambda, PerkinElmer, USA) at 232.8 nm.Results and discussion. In a comparative study of the mucoadhesive properties of polymer samples, IPC compacts showed a mucoadhesion capacity comparable to that of poly(2-ethyl-2-oxazoline); at the same time, compacts from physical mixtures (PM) and C971 are inferior in terms of the separation force to IPC samples, however, POZes dissolve in an artificial saliva medium, that is, they are not suitable as dosage forms for buccal delivery. For 5 hours of the experiment to assess the swelling capacity, the IPC matrices did not change significantly, which can ensure their comfortable use as carriers for buccal delivery. When evaluating the release of metformin from polymer matrices (with weight ratio MF/IPC 1: 0.5), the most complete release (more than 90 %) is observed from both IPC matrices compared to matrices of PM and individual polymers.Conclusion. Polycomplex matrix systems based on C971-POZ (50 kDa) and C971-POZ (500 kDa) are suitable for buccal delivery of metformin.