A fej-nyaki daganatok ma Magyarországon a 4. leggyakoribb daganatos betegségek. Az etiológiai faktorokat tekintve vezető tényező a dohányzás és az alkoholfogyasztás. Ezek hiányában a HPV-pozitivitás számít oki tényezőnek. Az eredményes kezelés egyénre szabottan ötvözi a sebészi, kemo-, sugár- és immunterápiát. Munkánkban a kemoterápiás szerek mellékhatásprofiljának szűkítését próbáltuk csökkenteni két ismert és széles körben használt kemoterapeutikumot, ciszplatint és mitomicin C-t tartalmazó, új nanotechnológiai gyógyszerbeviteli rendszer kialakításával. A poli(vinil-alkohol)-tartalmú szintetikus polimerből gyógyszerbeviteli rendszert alakítottunk ki, mely tartalmazza a ciszplatin vagy mitomicin C kemoterapeutikumot. A nanotechnológiai gyógyszerleadó rendszer a célterületre való bevitel után a hatóanyagot koncentrációfüggő mennyiségben, időkontrolláltan adja le a kívánt hatás eléréséhez. Vizsgált szintetikus polimerünk a mukoadhezív, biokompatibilis, biodegradábilis tulajdonságait kiaknázva a hatóanyag leadása után eliminálódik. Ez a korszerű nanotechnológiai gyógyszerbeviteli rendszer egy új lokális kemoterápia lehetőségét veti fel, mellyel nagy fokban csökkenthetjük a kemoterápiás szerek ismert, sok esetben a kemoterápiás kezelés felfüggesztését okozó, súlyos, életet veszélyeztető mellékhatásait. Orv Hetil. 2024; 165(10): 370–378.
Head and neck tumours are the 4th most common cancers in Hungary today. In terms of etiological factors, smoking and alcohol consumption are the leading ones. In the absence of these, HPV positivity counts as a causal factor. The successful treatment combines surgery, chemo-, radio- and immunotherapy in an individualized manner. In our study, we tried to narrow down the side-effect profile of two well-known and widely used chemotherapeutic agents, namely, cisplatin and mitomycin C, using a newly designed drug delivery system. We created a drug delivery system from the biocompatible polyvinyl alcohol-containing synthetic polymer, which encapsulates the chemoterapeutic agents cisplatin or mitomycin C. The drug delivery system produced by nanotechnology, after application to the target area, the active substance is released in a concentration-dependent amount in a time-controlled manner to achieve the desired effect. Exploiting the mucoadhesive, biocompatible, biodegradable properties of our tested synthetic polymer, the active ingredient is eliminated after release. This new nanotechnological drug delivery system raises the possibility of a new local chemotherapy, with which we can greatly reduce the known, serious life-threatening side effects of chemoterapeutic agents, which in many cases result in the suspension of chemoterapeutic treatment. Orv Hetil. 2024; 165(10): 370–378.
Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 2015; 136: E359–E386.
National Cancer Registry. [Nemzeti Rákregiszter.] Available from: https://onkol.hu/nemzeti-rakregiszter/ [accessed: 25 Nov, 2023]. [Hungarian]
Wéber A, Szatmári I, Dobozi M, et al. Comparison of Hungarian Central Statistical Office’s causes of death data with the database of the Hungarian National Cancer Registry. Lessons from a record linkage. [A Központi Statisztikai Hivatal halálozási adatainak összevetése a Nemzeti Rákregiszter adatbázisával. Egy adat-összekapcsolás tanulságai.] Orv Hetil. 2022; 163: 1481–1489. [Hungarian]
Orosz E, Gombos K, Petrevszky N, et al. Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model. Sci Rep. 2020; 10: 40. Erratum: Sci Rep. 2020; 10: 5664.
Jethwa AR, Khariwala SS. Tobacco-related carcinogenesis in head and neck cancer. Cancer Metastasis Rev. 2017; 36: 411–423.
Johnson DE, Burtness B, Leemans CR, et al. Head and neck squamous cell carcinoma. Nat Rev Dis Primers 2020; 6: 92.
McDermott JD, Bowles DW. Epidemiology of head and neck squamous cell carcinomas: impact on staging and prevention strategies. Curr Treat Options Oncol. 2019; 20: 43.
Tumban E. A current update on human papillomavirus-associated head and neck cancers. Viruses 2019; 11: 922.
Mesia R, Iglesias L, Lambea J, et al. SEOM clinical guidelines for the treatment of head and neck cancer (2020). Clin Transl Oncol. 2021; 23: 913–921. Erratum: Clin Transl Oncol. 2021; 23: 1001.
Plavc G, Strojan P. Combining radiotherapy and immunotherapy in definitive treatment of head and neck squamous cell carcinoma. Review of current clinical trials. Radiol Oncol. 2020; 54: 377–393.
Ferenczi Ö, Major T, Takácsi-Nagy Z. The role of brachytherapy in the curative treatment of oral cavity tumors. [A brachytherapia szerepe az ajak-szájüregi daganatok kuratív ellátásában.] Orv Hetil. 2021; 162: 1471–1479. [Hungarian]
Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014; 740: 364–378.
Makovec T. Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol. 2019; 53: 148–158.
Zhang C, Xu C, Gao X, et al. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics 2022; 12: 2115–2132.
Wang X, Zhou Y, Wang D, et al. Cisplatin-induced ototoxicity: from signaling network to therapeutic targets. Biomed Pharmacother. 2023; 157: 114045.
Qi L, Luo Q, Zhang Y, et al. Advances in toxicological research of the anticancer drug cisplatin. Chem Res Toxicol. 2019; 32: 1469–1486.
Szabó D, Kovács D, Endresz V, et al. Antifibrotic effect of mitomycin-C on human vocal cord fibroblasts. Laryngoscope 2019; 129: E255–E262.
Snodgrass RG, Collier AC, Coon AE, et al. Mitomycin C inhibits ribosomal RNA: a novel cytotoxic mechanism for bioreductive drugs. J Biol Chem. 2010; 285: 19068–19075.
Miranda MB, Hartmann JT, Al-Batran SE, et al. Mitomycin C and capecitabine in pretreated patients with metastatic gastric cancer: a multicenter phase II study. Cancer Res Clin Oncol. 2014; 140: 829–837.
Ospovat I, Siegelmann-Danieli N, Grenader T, et al. Mitomycin C and vinblastine: an active regimen in previously treated breast cancer patients. Tumori 2009; 95: 683–686.
Zhou W, Liu J, Mao D, et al. The clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C after transurethral resection of bladder tumour in patients with nonmuscular invasive bladder cancer: a meta-analysis. PLoS ONE 2022; 17: e0276453.
Merritt SR, Velasquez G, von Recum HA. Adjustable release of mitomycin C for inhibition of scar tissue formation after filtration surgery. Exp Eye Res. 2013; 116: 9–16.
Teus MA, de Benito-Llopis L, Alió JL. Mitomycin C in corneal refractive surgery. Surv Ophthalmol. 2009; 54: 487–502.
Stewart CE 4th, Kim JY. Application of mitomycin-C for head and neck keloids. Otolaryngol Head Neck Surg. 2006; 135: 946–950.
Haque Y, Kikuchi E, Kanemitsu T, et al. NII-electronic library service. Chem Pharm Bull. 1986; 34: 430–433.
Crooke ST, Bradner WT. Mitomycin C: a review. Cancer Treat Rev. 1976; 3: 121–139.
Abdelghafour MM, Deák A, Szabó D, et al. Use of self-assembled colloidal prodrug nanoparticles for controlled drug delivery of anticancer, antifibrotic and antibacterial mitomycin. Int J Mol Sci. 2022; 23: 6807.
Korsmeyer RW, Gurny R, Doelker E, et al. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm. 1983; 15: 25–35.
Rahim H, Khan MA, Badshah A, et al. Evaluation of prunus domestica gum as a novel tablet binder. Braz J Pharmaceutical Sci. 2014; 50: 195–202.
Kumar U, Islam S, Halder S, et al. Assessment of once daily sustained release hydrophilic matrix tablet of carvedilol. Dhaka Univ J Pharmaceutical Sci. 2017; 16: 43–53.
Freichel OL, Lippold BC. A new oral erosion controlled drug delivery system with a late burst in the release profile. Eur J Pharm Biopharm. 2000; 50: 345–351.
Sackett CK, Narasimhan B. Mathematical modeling of polymer erosion: consequences for drug delivery. Int J Pharm. 2011; 418: 104–114.
Fung LK, Saltzman WM. Polymeric implants for cancer chemotherapy. Adv Drug Deliv Rev. 1997; 26: 209–230.
Nomura T, Saikawa A, Morita S, et al. Pharmacokinetic characteristics and therapeutic effects of mitomycin C-dextran conjugates after intratumoural injection. J Control Release 1998; 52: 239–252.
Cheung RY, Ying Y, Rauth AM, et al. Biodegradable dextran-based microspheres for delivery of anticancer drug mitomycin C. Biomaterials 2005; 26: 5375–5385.
Cumming J, Allan L, Smyth JF. Encapsulation of mitomycin C in albumin microspheres markedly alters pharmacokinetics, drug quinone reduction in tumour tissue and antitumour activity. Implications for the drugs’ in vivo mechanism of action. Biochem Pharmacol. 1994; 47: 1345–1356.
Xi-Xiao Y, Jan-Hai C, Shi-Ting L, et al. Polybutylcyanoacrylate nanoparticles as a carrier for mitomycin C in rabbits bearing VX2-liver tumor. Regul Toxicol Pharmacol. 2006; 46: 211–217.
Ishiki N, Onishi H, Machida Y. Evaluation of antitumor and toxic side effects of mitomycin C-estradiol conjugates. Int J Pharm. 2004; 279: 81–93.
Liu Y, Li H, Shu XZ, et al. Crosslinked hyaluronan hydrogels containing mitomycin C reduce postoperative abdominal adhesions. Fertil Steril. 2005; 83(Suppl1): 1275–1283.
Chaudhuri B, Mondal B, Ray SK, et al. A novel biocompatible conducting polyvinyl alcohol (PVA)-polyvinylpyrrolidone (PVP)-hydroxyapatite (HAP) composite scaffolds for probable biological application. Colloids Surf B Biointerfaces 2016; 143: 71–80.
Zanin MH, Cerize NN, de Oliveira AM. Production of nanofibers by electrospinning technology: overview and application in cosmetics. In: Beck R, Guterres S, Pohlmann A. (eds) Nanocosmetics Nanomedicines. Springer, Berlin, Heidelberg, 2011; pp. 311–332. Available from: https://doi.org/10.1007/978-3-642-19792-5_16 [accessed: 25 Nov, 2023].
Thomas LV, Arun U, Remya S, et al. A biodegradable and biocompatible PVA-citric acid polyester with potential applications as matrix for vascular tissue engineering. J Mater Sci Mater Med. 2009; 20(Suppl 1): S259–S269.
Leone G, Consumi M, Greco G, et al. A PVA/PVP hydrogel for human lens substitution: synthesis, rheological characterization, and in vitro biocompatibility. J Biomed Mater Res B Appl Biomater. 2011; 97B: 278–288.
Picone P, Sabatino MA, Ajovalasit A, et al. Biocompatibility, hemocompatibility and antimicrobial properties of xyloglucan-based hydrogel film for wound healing application. Int J Biol Macromol. 2019; 121: 784–795.
Yan E, Fan Y, Sun Z, et al. Biocompatible core-shell electrospun nanofibers as potential application for chemotherapy against ovary cancer. Mater Sci Eng C. 2014; 41: 217–223.
Kamoun EA, Kenawy E-RS, Tamer TM, et al. Poly (vinyl alcohol)-alginate physically crosslinked hydrogel membranes for wound dressing applications: characterization and bio-evaluation. Arabian J Chem. 2015; 8: 38–47.
Noguchi T, Yamamuro T, Oka M, et al. Poly (vinyl alcohol) hydrogel as an artificial articular cartilage: evaluation of biocompatibility. J Appl Biomater. 1991; 2: 101–107.
Manavitehrani I, Rabiee M, Parviz M, et al. Preparation, characterization and controlled release investigation of biocompatible pH-sensitive PVA/PAA hydrogels. Macromol Symp. 2010; 296: 457–465.
Ikeuchi-Takahashi Y, Ishihara C, Onishi H. Evaluation of polyvinyl alcohols as mucoadhesive polymers for mucoadhesive buccal tablets prepared by direct compression. Drug Dev Ind Pharm. 2017; 43: 1489–1500.
Peppas NA, Mongia NK. Ultrapure poly(vinyl alcohol) hydrogels with mucoadhesive drug delivery characteristics. Eur J Pharm Biopharm. 1997; 43: 51–58.
Singh I, Rana V. Techniques for the assessment of mucoadhesion in drug delivery systems: an overview. J Adhes Sci Technol. 2012; 26: 2251–2267.
Leitner V, Walker G, Bernkop-Schnürch A. Thiolated polymers: evidence for the formation of disulphide bonds with mucus glycoproteins. Eur J Pharm Biopharm. 2003; 56: 207–714.
Albrecht K, Zirm EJ, Palmberger TF, et al. Preparation of thiomer microparticles and in vitro evaluation of parameters influencing their mucoadhesive properties. Drug Dev Ind Pharm. 2006; 32: 1149–1157.
Baker MI, Walsh SP, Schwartz Z, et al. A review of polyvinyl alcohol and its uses in cartilage and orthopedic applications. J Biomed Mater Res B Appl Biomater. 2012; 100: 1451–1457.
Chong SF, Smith AA, Zelikin AN. Microstructured, functional PVA hydrogels through bioconjugation with oligopeptides under physiological conditions. Small 2013; 9: 942–950.
Tadavarthy SM, Moller JH, Amplatz K. Polyvinyl alcohol (Ivalon) – a new embolic material. Am J Roentgenol Radium Ther Nucl Med. 1975; 125: 609–616.