Amphiphilic Polypeptides Obtained by the Post-Polymerization Modification of Poly(Glutamic Acid) and Their Evaluation as Delivery Systems for Hydrophobic Drugs

Abstract

Synthetic poly(amino acids) are a unique class of macromolecules imitating natural polypeptides and are widely considered as carriers for drug and gene delivery. In this work, we synthesized, characterized and studied the properties of amphiphilic copolymers obtained by the post-polymerization modification of poly(α,L-glutamic acid) with various hydrophobic and basic L-amino acids and D-glucosamine. The resulting glycopolypeptides were capable of forming nanoparticles that exhibited reduced macrophage uptake and were non-toxic to human lung epithelial cells (BEAS-2B). Moreover, the developed nanoparticles were suitable for loading hydrophobic cargo. In particular, paclitaxel nanoformulations had a size of 170–330 nm and demonstrated a high cytostatic efficacy against human lung adenocarcinoma (A549). In general, the obtained nanoparticles were comparable in terms of their characteristics and properties to those based on amphiphilic (glyco)polypeptides obtained by copolymerization methods.

Amphiphilic Polypeptides Obtained by Post-Polymerization Modification of Poly-l-Lysine as Systems for Combined Delivery of Paclitaxel and siRNA

“…In turn, the efficacy for the modification of poly-L-lysine copolymers with His was around 70% in all cases. The modification efficiency obtained in this work is consistent with recently published data on the modification of poly(αL-glutamic acid) with various amino acids and D-glucosamine [51].…”

“…The final residue was diluted with 0.5 mL of water, transferred to a glass, and dried by lyophilization. The amino-acid quantitative HPLC analysis was performed by a previously developed protocol [51] at the Chemical Analysis and Materials Research Center of SPbU Research Park.…”

“…The filtrates were collected and freeze dried. The lyophilized samples were dissolved in acetonitrile and analyzed by quantitative reversed-phase HPLC using a previously reported protocol [51]. The analysis was carried out at the Chemical Analysis and Materials Research Centre of SPbU Research Park.…”

“…Then, the tube was put into 12 mL PBS (0.01 M, pH 7.4) (external solution) and shaken at 37 • C. At predetermined time intervals, 3 mL of external solution was withdrawn for analysis and 3 mL of fresh pre-warmed PBS was added. Then, the collected samples were freeze dried and the PTX amount was analyzed by reversed-phase HPLC using a previously reported protocol [51]. The analysis was carried out at the Chemical Analysis and Materials Research Centre of SPbU Research Park.…”

Advanced hybrid silica nanoparticles with pH-responsive diblock copolymer brushes: optimized design for controlled doxorubicin loading and release in cancer therapy

“…31 Higher hydrophobicity in nanosystems can result in poor cellular uptake, leading to lower cytotoxic effects. 32 The reduced cytotoxic effects observed in loaded nanosystems could be attributed to the interaction of DOX with the nanoparticles. Additionally, differences in cellular uptake may contribute to the varying cytotoxic effects.…”