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1.
Int J Biol Macromol ; 123: 97-107, 2019 Feb 15.
Article in English | MEDLINE | ID: mdl-30419326

ABSTRACT

Our current understanding of the biophysicochemical interactions at nano-bio interfaces is still very limited. Surface plasmon resonance (SPR) is a powerful tool for understanding the real-time kinetics of protein binding on the surface of nanoparticles (NPs) but has been least exploited for this purpose. In this study, we demonstrated the interaction of negatively charged poly lactic-co-glycolic acid (PLGA) NPs and positively charged chitosan oligosaccharide (COS)-coated PLGA NPs with two model proteins, namely bovine serum albumin (BSA) and hen egg white lysozyme (LYZ), at the physiological pH of 7.4. Various biophysical characterization techniques were employed to elucidate the influence of surface charge of NPs on protein interaction. SPR investigations revealed the binding affinity and binding kinetics involved in nanoparticle-protein interactions. These results confirmed that the affinity of both types of NPs towards positively charged LYZ was much greater than that for negatively charged BSA, which was also in accordance with the results of the adsorption studies. Our results demonstrate that the surface properties of the interacting species play a dominant role during protein-nanoparticle interactions, apart from the net charge on their individual surfaces. The information obtained from this study adds significant value to the biophysicochemical toolbox for characterization of nano-bio interactions.


Subject(s)
Nanoparticles/chemistry , Adsorption/drug effects , Chitosan/chemistry , Kinetics , Muramidase/chemistry , Oligosaccharides/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Protein Interaction Domains and Motifs/drug effects , Serum Albumin, Bovine/chemistry , Surface Plasmon Resonance/methods , Surface Properties/drug effects
2.
Curr Gene Ther ; 17(2): 170-183, 2017.
Article in English | MEDLINE | ID: mdl-28494742

ABSTRACT

BACKGROUND: Recent integrated approaches involving nanotechnology and gene therapy have accelerated development of efficient drug delivery to the central nervous system (CNS). Neurodegenerative disorders are closely associated with genetic inheritance and mutation. MATERIALS: Nanotechnology has allowed effective engineering of various such polymeric structures. Moreover, availability of a wide array of polymeric materials has enabled fabrication of biocompatible and biodegradable delivery vehicles. Our manuscript focuses on the ideal features and properties of polymeric nanoparticles that have enabled successful gene therapy for neurodegenerative disorders, as well as the challenges that are posing difficulties in their practical application. We have highlighted these aspects through examples of polymeric nanoparticles that have exhibited therapeutic promise in the treatment of neurological disorders and mutations. METHODS: Complete cure of these diseases is a challenging task and gene therapy appears as a realistic approach for their treatment. Gene therapy allows effective replacement or suppression of faulty genes, thereby increasing chances for neuron survival and repair. However, successful delivery of naked genetic material to CNS faces severe obstacles due to possible degradation and restricted transportation of these biological entities across the blood brain barrier (BBB). Structurally, the BBB is composed of several tight junctions, making the membrane highly selective towards the entry of molecules. CONCLUSION: In order to target BBB for treating neurodegenerative diseases, it is essential to develop a tailor-made system that may not only cross this barrier, but also effectively modulate the expression of disease-causing genes. Stabilization of therapeutic genes and their effective, targeted delivery may be possible using polymeric nanoparticles as carriers.


Subject(s)
Genetic Therapy/methods , Nanoparticles/administration & dosage , Neurodegenerative Diseases/therapy , Polymers/administration & dosage , Animals , Drug Carriers/chemistry , Drug Delivery Systems/methods , Gene Transfer Techniques , Humans , Nanoparticles/chemistry , Nanotechnology/methods , Neurodegenerative Diseases/genetics , Polymers/chemistry
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