Abstract
Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting sideeffects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach.
In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies.
Buccal tablets were designed to deliver 5-FU locoregionally to the cancer lesions of the oral cavity. Tablets were prepared using a drug loaded matrix of acrylic/methacrylic acid copolymer containing 1% (w/w) of 5-FU and applied on 3D outgrowths. The drug release from tablets appeared to be sufficient to induce cell death as confirmed by transmission electron microscopy and enzymatic assay (TUNEL). After 120 h of treatment, when about 90% of the drug had been discharged from the tablets into the culture environment, 5-FU caused loss of cell-cell communications and apoptotic cell death. After 192 h, a complete disaggregation of the 3D oral outgrowths and the death of all the cells was observed.
Buccal matrix tablets could be considered a promising new approach to the locoregional treatment of OSCC. Risks of systemic toxicity are avoided since very low drug doses are delivered.
Keywords: 5-Fluorouracil, Locoregional drug delivery, Oral squamous cell carcinoma, Buccal tablets, Tissue engineering, 3D oral outgrowths, malignant lesions, cell death, oral cavity, systemic toxicity.
Current Pharmaceutical Design
Title:Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three- Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile Delivery by Drug-Loaded Matrix Tablets
Volume: 18 Issue: 34
Author(s): Giuseppina Campisi, Libero Italo Giannola, Alberto Fucarino, Antonella Marino Gammazza, Alessandro Pitruzzella, Vito Marciano, Viviana De Caro, Maria Gabriella Siragusa, Giulia Giandalia, Domenico Compilato, Stephen T. Holgate, Donna E. Davies, Felicia Farina, Giovanni Zummo, Carlo Paderni and Fabio Bucchieri
Affiliation:
Keywords: 5-Fluorouracil, Locoregional drug delivery, Oral squamous cell carcinoma, Buccal tablets, Tissue engineering, 3D oral outgrowths, malignant lesions, cell death, oral cavity, systemic toxicity.
Abstract: Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting sideeffects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach.
In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies.
Buccal tablets were designed to deliver 5-FU locoregionally to the cancer lesions of the oral cavity. Tablets were prepared using a drug loaded matrix of acrylic/methacrylic acid copolymer containing 1% (w/w) of 5-FU and applied on 3D outgrowths. The drug release from tablets appeared to be sufficient to induce cell death as confirmed by transmission electron microscopy and enzymatic assay (TUNEL). After 120 h of treatment, when about 90% of the drug had been discharged from the tablets into the culture environment, 5-FU caused loss of cell-cell communications and apoptotic cell death. After 192 h, a complete disaggregation of the 3D oral outgrowths and the death of all the cells was observed.
Buccal matrix tablets could be considered a promising new approach to the locoregional treatment of OSCC. Risks of systemic toxicity are avoided since very low drug doses are delivered.
Export Options
About this article
Cite this article as:
Campisi Giuseppina, Italo Giannola Libero, Fucarino Alberto, Marino Gammazza Antonella, Pitruzzella Alessandro, Marciano Vito, De Caro Viviana, Gabriella Siragusa Maria, Giandalia Giulia, Compilato Domenico, T. Holgate Stephen, E. Davies Donna, Farina Felicia, Zummo Giovanni, Paderni Carlo and Bucchieri Fabio, Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three- Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile Delivery by Drug-Loaded Matrix Tablets, Current Pharmaceutical Design 2012; 18 (34) . https://dx.doi.org/10.2174/138161212803307536
DOI https://dx.doi.org/10.2174/138161212803307536 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Marine Derived Anticancer Drugs Targeting Microtubule
Recent Patents on Anti-Cancer Drug Discovery Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: “Reverse Pharmacology” and “Bedside to Bench” Approach
Current Drug Targets LPS/TLR4 Pathways in Breast Cancer: Insights into Cell Signalling
Current Medicinal Chemistry Overcoming Drug Resistance by Enhancing Apoptosis of Tumor Cells
Current Cancer Drug Targets Proteomic Approaches for the Study of Transgelins as Tumor-associated Proteins and Potential Biomarkers
Current Proteomics Predictive Biomarkers to Tyrosine Kinase Inhibitors for the Epidermal Growth Factor Receptor in Non-Small-Cell Lung Cancer
Current Drug Targets Lung Cancer: Are we up to the Challenge?
Current Genomics Surgical Management of Mullerian Duct Anomalies
Current Women`s Health Reviews Promotion of Cervical Cancer Cell Proliferation by miR-130b Expression Level Changes and Inhibition of its Apoptosis by Targeting CDKN1A Gene
Current Cancer Drug Targets Versatility of Cancer Associated Fibroblasts: Commendable Targets for Anti-tumor Therapy
Current Drug Targets Class II Phosphoinositide 3-Kinases as Potential Novel Drug Targets
Current Signal Transduction Therapy Extra-telomeric Functions of Human Telomerase: Cancer, Mitochondria and Oxidative Stress
Current Pharmaceutical Design Targeting mTOR: Evaluating the Therapeutic Potential of Resveratrol for Cancer Treatment
Anti-Cancer Agents in Medicinal Chemistry Oral and Dental Considerations in the Management of Leukemic Children
Applied Clinical Research, Clinical Trials and Regulatory Affairs Metronomic Therapy for Multi Relapsed/Refractory Lymphoma. A Pilot Study
Current Angiogenesis (Discontinued) Pleural Fluid Analysis for Evaluating Pleural Effusions
Current Respiratory Medicine Reviews Dendritic Cells: More Than Just Adaptive Immunity Inducers?
Current Immunology Reviews (Discontinued) The Role of ING Tumor Suppressors in UV Stress Response and Melanoma Progression
Current Drug Targets Rab GTPases, Membrane Trafficking and Diseases
Current Drug Targets Dual-modality Chemo-photodynamic Therapy Using RB and DOX as Anti-cancer Drugs by PAMAM-grafted Hollow Porous Silica Nanoparticles
Current Nanoscience