Formulation and Development of Bioadhesive Oral Films Containing <i>Usnea barbata</i> (L.) F.H.Wigg Dry Ethanol Extract (F-UBE-HPC) with Antimicrobial and Anticancer Properties for Potential Use in Oral Cancer Complementary Therapy
Violeta Popovici,
Elena Matei,
Georgeta-Camelia Cozaru,
Laura Bucur,
Cerasela Elena Gîrd,
Verginica Schröder,
Emma Adriana Ozon,
Iulian Sarbu,
Adina Magdalena Musuc,
Irina Atkinson,
Adriana Rusu,
Simona Petrescu,
Raul-Augustin Mitran,
Mihai Anastasescu,
Aureliana Caraiane,
Dumitru Lupuliasa,
Mariana Aschie,
Victoria Badea
Affiliations
Violeta Popovici
Department of Microbiology and Immunology, Faculty of Dental Medicine, Ovidius University of Constanta, 7 Ilarie Voronca Street, 900684 Constanta, Romania
Elena Matei
Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology, Ovidius University of Constanta, CEDMOG, 145 Tomis Blvd., 900591 Constanta, Romania
Georgeta-Camelia Cozaru
Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology, Ovidius University of Constanta, CEDMOG, 145 Tomis Blvd., 900591 Constanta, Romania
Laura Bucur
Department of Pharmacognosy, Faculty of Pharmacy, Ovidius University of Constanta, 6 Capitan Al. Serbanescu Street, 900001 Constanta, Romania
Cerasela Elena Gîrd
Department of Pharmacognosy, Phytochemistry, and Phytotherapy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania
Verginica Schröder
Department of Cellular and Molecular Biology, Faculty of Pharmacy, Ovidius University of Constanta, 6 Capitan Al. Serbanescu Street, 900001 Constanta, Romania
Emma Adriana Ozon
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania
Iulian Sarbu
Department of Pharmaceutical Physics and Biophysics, Drug Industry and Pharmaceutical Biotechnologies, Faculty of Pharmacy, “Titu Maiorescu” University, 004051 Bucharest, Romania
Adina Magdalena Musuc
“Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Spl. Independentei, 060021 Bucharest, Romania
Irina Atkinson
“Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Spl. Independentei, 060021 Bucharest, Romania
Adriana Rusu
“Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Spl. Independentei, 060021 Bucharest, Romania
Simona Petrescu
“Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Spl. Independentei, 060021 Bucharest, Romania
Raul-Augustin Mitran
“Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Spl. Independentei, 060021 Bucharest, Romania
Mihai Anastasescu
“Ilie Murgulescu” Institute of Physical Chemistry, Romanian Academy, 202 Spl. Independentei, 060021 Bucharest, Romania
Aureliana Caraiane
Department of Oral Rehabilitation, Faculty of Dental Medicine, Ovidius University of Constanta, 7 Ilarie Voronca Street, 900684 Constanta, Romania
Dumitru Lupuliasa
Department of Pharmaceutical Technology and Biopharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 6 Traian Vuia Street, 020956 Bucharest, Romania
Mariana Aschie
Center for Research and Development of the Morphological and Genetic Studies of Malignant Pathology, Ovidius University of Constanta, CEDMOG, 145 Tomis Blvd., 900591 Constanta, Romania
Victoria Badea
Department of Microbiology and Immunology, Faculty of Dental Medicine, Ovidius University of Constanta, 7 Ilarie Voronca Street, 900684 Constanta, Romania
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.
