Immunocompatibility and Toxicity Studies of Poly‐L‐Lysine Nanocapsules in Sprague–Dawley Rats for Drug‐Delivery Applications

Abstract

Poly-L-Lysine (PLL) nanocapsules are the emerging drug-delivery vehicle for the therapeutics of targeted diseases. The study was designed for the synthesis and characterization of PLL nanocapsules and to know its immunocompatibility and toxicity behavior for in vivo drug-delivery applications. Alteration in hematologic parameters, immunomodulatory gene expression by RT-PCR studies, toxicity markers status, immunoblotting of major inflammatory marker proteins, and histopathologic studies from major tissues of rat after intravenous administration of PLL nanocapsules after 30 days were assessed. In vivo toxicity markers activity, hematologic parameters alteration, and RT-PCR analysis of important immunomodulatory genes such as monocyte chemotactic protein-1(MCP 1), tumor necrosis factor-alpha (TNF-α), Intercellular adhesion molecule-1 (ICAM-1), and interleukin-6 (IL-6) showed least changes when compared with control. The immunoblotting of major inflammatory markers such as cyclooxygenase-2 (COX-2), lipo-oxygenase-15 (LOX-15), and nitric oxide synthase (NOS) found have least expression showing the immunocompatibility of PLL nanocapsules. Histopathologic studies of important tissues showed almost normal architecture after treatment using different concentration of PLL nanocapsules after the experimental period. The results showed a promising outcome and further confirmed the immunocompatibility and non-toxicity of PLL nanocapsules in vivo for drug-delivery applications.

In vitro toxicity studies of biodegradable, polyelectrolyte nanocapsules

“…demonstrating immunocompatibility and low toxicity of these nanocapsules. 34 In contrast to NC5, negatively charged PGA-terminated NC6 did not cause RBC aggregation and hemolysis. However, although NC6 did not influence PBMC viability, it affected the morphology of monocytes within PBMC population, most probably by increased phagocytosis of the nanomaterial.…”

Evaluation and comparison of cytotoxicity, genotoxicity, and apoptotic effects of poly-l-lysine/plasmid DNA micro- and nanoparticles

“…[8][9][10][11][12] PLL is a natural cationic polymer with positively charged side chain, due to the presence of amino acid lysine as the repeat unit, this polymer is biodegradable and this property considers it as a remarkable candidate for in vivo applications such as drug delivery and cell tracking. [13][14][15] PLL polymer can act as a vehicle for different cargoes such as drugs, peptides, and genes 16,17 and also as a promising coating agent for improving biocompatibility of different nanoparticles for cell tracking process. 18,19 Since the constitution of polyelectrolyte complexes between PLL and DNA was recognized, PLL has been extensively used as a nonviral gene carrier.…”

Evaluation of an Analogue of the Marine ε-PLL Peptide as a Ligand of G-quadruplex DNA Structures

“…On the other side, α-poly-L-lysine (α-PLL) is a synthetic poly(amino acid) successfully used in different biotechnological applications, e.g., in biomass production by microalgae Chlorella ellipsoidea [10]. α-and ε-PLL peptides are well soluble in aqueous media, biodegradable, and environmental-friendly [11], and both are good candidates as drug delivery agents due to their polycationic nature [11,12]. Even though dendrimeric α,ε-poly-L-lysines had been previously realized for the compacting and delivery of oligonucleotides [13], a synthetic approach to linear PLLs with sequential α-and ε-peptide bonds (α,ε-PLLs, Figure 1) was firstly reported by Roviello et al alongside with the initial biological assessment of α,ε-PLLs [13][14][15].…”