VINORELBINE-LOADED pH-SENSITIVE LIPOSOMES: DEVELOPMENT, CHARACTERIZATION AND IN VITRO EVALUATION

Vinorelbine (NVB) is an anti-mitotic drug used to treat multiple types of cancers, demonstrating a high antitumor activity and low neurotoxicity.The pH-sensitive liposomes (PSL) undergo destabilization of the vesicular membranes in the acidic environment of tumours which triggers the release of active substance at the tumour site.The aim of this study was to design and evaluate the NVB-PSL formulations in non-small cell lung cancer (NSCLC) cell lines regarding their anti-tumour effect.The liposomes were obtained using the thin lipid film hydration method.An optimization study was performed using the Design of Experiments (DoE) methodology.The obtained liposomes were characterised in terms of particle size, homogeneity, surface charge, encapsulation efficiency and NVB content.The DoE analysis showed significant relation between the chosen factors (the ratio and concentration of lipids and NVB concentration) and the responses, which enabled the prediction of an optimum PSL formulation.We performed the in vitro release study at different pH values and the results demonstrated a pH-dependent release profile of the NVB-PSL optimal formulation.The in vitro evaluation of the optimal NVB-PSL formulation on two NSCLC cell lines revealed significant cytotoxicity of the liposomal formulations.In conclusion, this study reports the successful formulation and characterization of NVB-PSL as promising tool in NSCLC therapy. RezumatVinorelbina (NVB) este o substan anti-mitotic utilizat pentru tratarea mai multor tipuri de cancer, demonstrnd o activitate antitumoral ridicat i neurotoxicitate sczut.Lipozomii cu cedare dependent de pH (PSL) sufer destabilizarea veziculelor lipozomale n mediul acid al tumorilor care declaneaz eliberarea NVB la int.Scopul acestui studiu a fost prepararea i evaluarea formulrilor NVB-PSL pe liniile celulare de cancer pulmonar non-microcelular (NSCLC) n ceea ce privete efectul antitumoral.Lipozomii au fost obinui folosind metoda hidratrii filmului lipidic.A fost realizat un studiu de optimizare folosind metodologia Design of Experiments (DoE).Lipozomii obinui au fost caracterizai sub aspectul dimensiunii particulelor, omogenitii, sarcinii de suprafa, eficienei ncapsulrii i coninutului de NVB.Analiza DoE a demonstrat existena unei relaii semnificative ntre factorii alei (raportul i concentraia de lipide i concentraia de NVB) i rspunsuri, ceea ce a permis predicia unei formulri optime de PSL.S-a efectuat studiul de cedare a NVB in vitro la diferite valori ale pH-ului, iar rezultatele au demonstrat un profil de eliberare dependent de pH a formulrii optime.Evaluarea in vitro a formulrii optime pe dou linii celulare de NSCLC a demonstrat o citotoxicitate semnificativ a formulrilor lipozomale.n concluzie, acest studiu raporteaz formularea i caracterizarea cu succes a NVB-PSL ca instrument promitor n terapia NSCLC.