Julia Malinovskaya, Julia Kotova, Pavel Melnikov, Nadezhda Osipova, Ludmila Vanchugova and Svetlana Gelperina
Mendeleev University of Chemical Technology, Russia V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology, Russia
Scientific Tracks Abstracts: J Nanomed Nanotechnol
Statement of the Problem: Coating of the poly(lactide-co-glycolide) nanoparticles (PLGA NP) with the functional polymeric shells is a promising strategy for optimization of their in vivo performance [1-4]. However, the integrity of such core-shell nanocarriers upon their contact with the biological objects is not fully elucidated. In the present study, the integrity of the PLGA NP coated with the shells consisting of either human serum albumin (PLGA-HSA NP) or divinyl ether-maleic anhydride copolymer (PLGA-DIVEMA NP) upon their internalization in glioma Gl261 cells was evaluated using confocal laser scanning microscopy (CLSM). Methodology & Theoretical Orientation: For the NP visualization using CLSM both the core and the shells were labeled with the covalently bound fluorescent dyes (shell: Cy3, core: Cy5). The core PLGA-Cy5 NP and the PLGADIVEMA NP were obtained by the high-pressure homogenization technique [5]. The integrity of the core-shell structures upon internalization in the cells was evaluated by CLSM using the colocalization analysis between the NP core and the shell. Findings: The PLGA-HSA NP had the average size of 100-170 nm and negative zeta-potential of –10-30 mV. The PLGADIVEMA NP exhibited the average size of 180-260 nm and negative zeta-potential of –30-50 mV. All core-shell NP appeared to be stable in the cell–free medium; however, their integrity upon intracellular uptake depended on the shell type. Thus, in the case of the PLGA-DIVEMA NP, the colocalization coefficient of <0.5 (between PLGA and DIVEMA) as well as the DIVEMA-Cy3 intracellular fluorescence observed already at early time points of incubation suggested that the shell was at least partly dissociated from the core. In contrast, the PLGA-HSA NP preserved their integrity within 45 min of incubation. Conclusion & Significance: Evaluation of the core-shell nanocarriers’ stability in the biological environment is warrant in the early stage of the preclinical studies.
Recent publications:
1. Taiki Miyazawa Mayuko Itaya, Gregor C Burdeos Kiyotaka Nakagawa Teruo Miyazawa. A Critical Review of the Use of Surfactant-Coated Nanoparticles in Nanomedicine and Food Nanotechnology. International Journal of Nanomedicine 2021:16 3937–3999
2. Xinlong Wang, Yuheng Liang, Siyang Fei, Haibing He, Yu Zhang, Tian Yin, Xing Tang. Formulation and Pharmacokinetics of HSA-core and PLGA-shell Nanoparticles for Delivering Gemcitabine. AAPS PharmSciTech (# 2017) DOI: 10.1208/ s12249-017-0888-9
3. Zahra Mahdavi, Hamed Rezvani, Mostafa Keshavarz Moraveji. Core–shell nanoparticles used in drug delivery microfluidics: a review. RSC Adv., 2020, 10, 18280. DOI: 10.1039/d0ra01032d
4. Jiang J, Zhong X, Zhang H and Wang C. A novel corona core-shell nanoparticle for enhanced intracellular drug delivery. Mol Med Rep 21: 1965-1972, 2020
5. Malinovskaya Y, Melnikov P, Baklaushev V, Gabashvili A, Osipova N, Mantrov S, Ermolenko Y, Maksimenko O, Gorshkova M, Balabanyan V, Kreuter J, Gelperina S. Delivery of doxorubicin-loaded PLGA nanoparticles into U87 human glioblastoma cells. Int J Pharm. 2017 May 30;524(1-2):77-90. doi: 10.1016/j.ijpharm.2017.03.049.
Julia Malinovskaya received her PhD in Pharmacology from the Lomonosov Moscow State University in the field of brain delivery in the research group of Prof. Svetlana Gelperina in the laboratory for drug delivery systems. Previously she obtained her Master’s in Pharmacy from the First Moscow MedicalUniversity, andhadaninternshipinthelaboratoryofProf. BakowskyattheInstituteforPharmaceuticaltechnology, PhilippsUniversityofMarburg. Her current focus is the development of polymeric nanoparticle-based drug delivery formulations, characterization, in vitro and in vivo evaluation.