Formulation and Development of Bioadhesive Oral Films Containing Usnea barbata (L.) F.H.Wigg Dry Ethanol Extract (F-UBE-HPC) with Antimicrobial and Anticancer Properties for Potential Use in Oral Cancer Complementary Therapy

Abstract

Medical research explores plant extracts’ properties to obtain potential anticancer drugs. The present study aims to formulate, develop, and characterize the bioadhesive oral films containing Usnea barbata (L.) dry ethanol extract (F-UBE-HPC) and to investigate their anticancer potential for possible use in oral cancer therapy. The physicochemical and morphological properties of the bioadhesive oral films were analyzed through Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Atomic Force Microscopy (AFM), thermogravimetric analysis (TG), and X-ray diffraction techniques. Pharmacotechnical evaluation (consisting of the measurement of the specific parameters: weight uniformity, thickness, folding endurance, tensile strength, elongation, moisture content, pH, disintegration time, swelling rate, and ex vivo mucoadhesion time) completed the bioadhesive films’ analysis. Next, oxidative stress, caspase 3/7 activity, nuclear condensation, lysosomal activity, and DNA synthesis induced by F-UBE-HPC in normal blood cell cultures and oral epithelial squamous cell carcinoma (CLS-354) cell line and its influence on both cell types’ division and proliferation was evaluated. The results reveal that each F-UBE-HPC contains 0.330 mg dry extract with a usnic acid (UA) content of 0.036 mg. The bioadhesive oral films are thin (0.093 ± 0.002 mm), reveal a neutral pH (7.10 ± 0.02), a disintegration time of 118 ± 3.16 s, an ex vivo bioadhesion time of 98 ± 3.58 min, and show a swelling ratio after 6 h of 289 ± 5.82%, being suitable for application on the oral mucosa. They displayed in vitro anticancer activity on CLS-354 tumor cells. By considerably increasing cellular oxidative stress and caspase 3/7 activity, they triggered apoptotic processes in oral cancer cells, inducing high levels of nuclear condensation and lysosomal activity, cell cycle arrest in G0/G1, and blocking DNA synthesis. All these properties lead to considering the UBE-loaded bioadhesive oral films suitable for potential application as a complementary therapy in oral cancer.

Design, Characterization, and Anticancer and Antimicrobial Activities of Mucoadhesive Oral Patches Loaded with Usnea barbata (L.) F. H. Wigg Ethanol Extract F-UBE-HPMC

“…Until the pharmaceutical formulation, our team studied U. barbata from the Calimani mountains for almost 6 years, according to current medicinal plant legislation [ 76 , 77 , 78 ]. In the present work, mucoadhesive oral patches containing U. barbata dry ethanol extract were manufactured and analyzed, compared to References (the same formulation without UBE).…”

ROS-Induced DNA-Damage and Autophagy in Oral Squamous Cell Carcinoma by Usnea barbata Oil Extract—An In Vitro Study

“…Terbinafine solution 10.1 mg/mL (Rompharm Company S.R.L., Otopeni, România) was selected as the standard for Candida sp. [ 47 ]. The solution of 5% P407 was used as a positive control [ 44 ].…”

“…Therefore, they are considered important bioactive representatives with pharmaceutical applications [ 37 ] as a potential source of anticancer [ 38 , 39 , 40 ] and antibiotic medicines [ 41 , 42 , 43 ]. Recently, a few authors performed lichens incorporation in different pharmaceutical formulations [ 44 , 45 , 46 , 47 , 48 , 49 ].…”

Three-Dimensional Printing Technologies in Oral Films Manufacturing—A Minireview

“…Their action can be topical [6][7][8] or systemic [9][10][11]. The variety of active ingredients contained in OF is wide: plant extracts [12][13][14][15], herbal compounds [16][17][18], nutraceuticals [19], conventional drugs [20][21][22][23][24][25][26], antibiotics [27], antivirals [28,29], vaccines [30], insulin [31], and other proteins [32].…”