Nanoarchitectonics of PLGA based polymeric nanoparticles with oseltamivir phosphate for lung cancer therapy: In vitro-in vivo evaluation

Yurtdas-Kirimliog G., Gogulu S., Guelec K., KIYAN H. T.

JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, cilt.67, 2022 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 67
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1016/j.jddst.2021.102996
  • Dergi Adı: JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Biotechnology Research Abstracts, EMBASE
  • Anahtar Kelimeler: Oseltamivir phosphate, PLGA, Pegylation, Antiangiogenic activity, Nanoarchitectonics, Lung cancer, EMBRYO CHORIOALLANTOIC MEMBRANE, DELIVERY, DRUG, FORMULATION, RELEASE, GROWTH, ACID, CYTOTOXICITY, DISSOLUTION, MODEL
  • Anadolu Üniversitesi Adresli: Evet

Özet

Oseltamivir phosphate (OSE) is an antiviral drug that also can inhibit tumor vascularization, growth and metastasis. The target of the present research was the delivery of OSE into the lung adenocarcinoma cells by means of developing nanosized, biocompatible and stealth nanoarchitectonics of pegylated PLGA NPs. For this goal, OSE encapsulated nanoarchitectonics of pegylated PLGA NPs were formulated and investigated for zeta potential, particle size, encapsulation efficiency, DSC, FT-IR, H-1-NMR and SEM analyses. In vitro release, cyto-toxicity, determination of apoptotic pathways and in vivo CAM assay were carried out. NPs exhibited smaller particle size, relatively higher EE%, spherical shape, amorphous matrix formation and biphasic prolonged release pattern (fitted Peppas-Sahlin and Weibull model). All NPs was found as 10(3) times more effective than OSE on cancerous cells. Flow cytometry was employed to evaluate the apoptotic pathways using the Annexin V-FITC/PI, FITC Active Caspase-3 staining assay and mitochondrial membrane potential determination tests. Activations on caspase-3 pathways made us think that OSE loaded pegylated PLGA NPs triggered to apoptosis using intrinsic pathway. Upon in vivo studies, PLGA-OSE 3 demonstrated moderate antiangiogenic activity. These results indicate that OSE loaded PLGA NPs (especially PLGA-OSE 3) were chosen as a promising candidate and a potent formulation to treat lung cancer.