###### Abstract  
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 peroxpiritrite and IL-1\(\alpha\) 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 peroxpiritrite and IL-1\(\alpha\) 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. collagen peptide; buccal delivery film; clinical study; homeopathy 2021 11 August 2021 11 August 2021 15 August 2021 11 August 202  
a high substantivity on the skin [9; 10; 11]. However, collagen is a high-molecular-weight protein and cannot be absorbed by the skin [10]. Thus, lower-molecular-weight collagen under 500 Da is composed of at most three amino acids, such as Gly-Pro-Hyp and Gly-Pro-Ala, as well as Hyp-Gly and Gly-Pro [12], called collagen hydrolysate, are frequently used to enhance the absorption of cosmetics [13] and effectiveness of collagen capsules as functional foods. On the other hand, The lower-molecular-weight collagen can be another protein due to it being just part of the peptide in whole collagen and when taken orally, as collagen passes through the gastrointestinal tract, it is mostly destroyed by digestive enzymes during first-pass metabolism [14]. Therefore, new technology for enhancing the absorption of high-molecular-weight protein collagen peptides without destroying them is needed. The buccal delivery system is a direct absorption method for materials to enter the body. This pathway has been widely used in the pharmaceutical industry because of its rapid absorption potential and high bioavailability, as it avoids the first-pass metabolism. Oral transmucosal material delivery was intensively explored regarding its local or systemic effects because the oral cavity has various advantages, including high vascularization of venous blood to the heart directly through the internal jugular vein [15]. Buccal films are easily attached to the mucosa, and the permeability of buccal mucosa is 4-4000 times better than that of skin [16]. In previous studies, low-molecular-weight polypeptides, such as collagen hydrolysate, which were under several thousand daltons, were passed through the buccal mucosa [13; 17; 18; 19; 20]. However, the buccal film attached to the mucosa is easily inhibited by saliva, leading to the destruction and loss of functional materials and rapid crumbling of the film. Therefore, double-layer film technology was applied in our study. The double-layer film was a composite film with a muco-adhesive layer (containing collagen peptides) and a protective layer, which prevented the enzymes in the saliva from destroying the collagen peptides and releasing them in one direction into the mucosa. Although various collagen functional food products are on the market, clinical studies on the functions of collagen are lacking. [PERSON] et al. asserted that a collagen drink significantly improved skin hydration, elasticity, roughness, and density compared to a placebo group after 12 weeks of clinical study [21].