In vitro and in vivo evaluation of levodopa-loaded nanoparticles for nose to brain delivery


ARISOY S., Sayiner O., ÇOMOĞLU T., ÖNAL D., ATALAY Ö., PEHLİVANOĞLU B.

PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, cilt.25, sa.6, ss.735-747, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 6
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1080/10837450.2020.1740257
  • Dergi Adı: PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Business Source Elite, Business Source Premier, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE
  • Sayfa Sayıları: ss.735-747
  • Anahtar Kelimeler: Nasal drug delivery, levodopa nanoparticles, PLGA, Parkinson disease, wheat germ aglutinine conjugation, in vivo Parkinson disease model, CONJUGATED PLGA NANOPARTICLES, PARKINSONS-DISEASE, DRUG-DELIVERY, CHITOSAN NANOPARTICLES, PLA-NANOPARTICLES, L-DOPA, MICROSPHERES, SIZE, FORMULATION, OPTIMIZATION
  • Ankara Üniversitesi Adresli: Evet

Özet

Parkinson's disease (PD) is a neurodegenerative disease which is characterized by the loss of dopaminergic neurons in the brain. Levodopa is the drug of choice in the treatment of PD but it exhibits low oral bioavailability (30%) and very low brain uptake due to its extensive metabolism by aromatic amino acid decarboxylase in the peripheral circulation. Moreover, levodopa has psychic, gastrointestinal, and cardiovascular side effects, and most importantly, short and frequent stimulation of dopamine receptors lead to undesirable conditions such as dyskinesia over time. The challenges are to increase the therapeutic efficiency, the bioavailability and decreasing the unfavourable side effects of levodopa. Biocompatible nano-sized drug carriers could address these challenges at molecular level. For this purpose, levodopa-loaded Poly (lactide-co-glycolide) acid nanoparticles were prepared by double emulsion-solvent evaporation method for nose to brain drug delivery. Parameters such as homogenization speed, and external and internal phase content were modified to reach the highest loading efficiency. F1-1 coded formulation showed prolonged release up to 9 h. Carbodiimide method was used for surface modification studies of nanoparticles. The efficacy of the selected nanoparticle formulation has been demonstrated by in vivo experiments in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced PD model in mice.