Amphiphilic polypeptides with prolonged enzymatic stability for the preparation of self-assembled nanobiomaterials

Tarasenko, I. I.; Zashikhina, Natalia; Guryanov, Ivan; Volokitina, M. V.; Biondi, Barbara; Fiorucci, Stefano; Formaggio, Fernando; Tennikova, Tatiana; Korzhikova-Vlakh, Evgenia

doi:10.1039/c8ra06324a

Cited by 18 publications

(20 citation statements)

References 55 publications

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“…Normally, the self-assembling of diblock amphiphilic polypeptides is readily aggregated. 28 There is literature reporting that the D-type polypeptide block contributed the stability in water, 12 and our results agree well with these reports. The nature of the biostability of poly(L-lysine) 33 -block-poly(Dphenylalanine) 14 is beneficial for its medical application.…”

Section: ■ Results and Discussionsupporting

confidence: 92%

Controlled Block Polypeptide Composed of d-Type Amino Acids: A Therapeutics Delivery Platform to Inhibit Biofilm Formation of Drug-Resistant Bacteria

Chen

Zhang

2020

ACS Appl. Bio Mater.

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Antibiotic resistance of bacteria has been widely developed due to biofilm protection and separating the bacteria from antibiotics. The phenomenon of biofilm inhibition or disassembly by D-amino acids (DAAs) has been reported recently, while it was also challenged by some other scientists. Presuming DAAs work for biofilms on the surface of bacteria, delivery of the DAAs to disease sites is important while small DAAs are easily removed by kidney. To resolve the above issues, it is urgent to develop a biofilm inhibitor. To achieve this goal, we synthesized D-type polypeptides via NCA ring-opening polymerization with the initiator of HMDS to generate poly(CBZ-L-lysine) 33 -block-poly(D-phenylalanine) 14 . After deprotection, the resultant polypeptides were converted into amphiphilic poly(L-lysine) 33 -blockpoly(D-phenylalanine) 14 , which can be self-assembled into well-defined homogeneous nanoparticles capable of capsulizing penicillin G. For the molecular weight of polypeptides resulting in various bioeffects, we prepared similar-sized polypeptides of an L-type equivalent polypeptide as control. The data from microbial experiments indicated that poly(L-lysine) 33 -block-poly(D-phenylalanine) 14 can inhibit biofilm formation of Bacillus subtilis at a low final concentration (24 μg/mL), much stronger than poly(L-lysine) 40 -block-poly(L-phenylalanine) 19 at the same concentration. This is the first report in that synthetic D-type polypeptides can inhibit biofilms of bacteria. Poly(L-lysine) 33 -block-poly(D-phenylalanine) 14 can be assembled into well-defined, biostable homogeneous nanoparticles. This research provides a potential solution to overcome bacteria antibiotic resistance from small molecules to material sciences and gives a unique angle to understand the current dispute if DAAs can disassemble the biofilms. Additionally, these nanoparticles have great potential in the development of nanomedicines with a longer circulation time in blood and this discovery has implications in developing antimicrobial nanodevices for therapy and basic scientific interest.

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Section: ■ Results and Discussionsupporting

confidence: 92%

Controlled Block Polypeptide Composed of d-Type Amino Acids: A Therapeutics Delivery Platform to Inhibit Biofilm Formation of Drug-Resistant Bacteria

Chen

Zhang

2020

ACS Appl. Bio Mater.

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Section: Resultsmentioning

confidence: 99%

“…The smaller average diameter of NPs determined from the TEM images can reflect the loss of water as the sample dried on the TEM grid. This is a well-known feature of soft self-assembled nanomaterials [42,43]. The high absolute value of ζ-potential was premised on the assumption of a potentially high stability of NPs in the dispersion against aggregation [44].…”

Section: Formation and Characterization Of Nanoparticlesmentioning

confidence: 99%

Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E

et al. 2020

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Polymyxins are peptide antibiotics that are highly efficient against many multidrug resistant pathogens. However, the poor stability of polymyxins in the bloodstream requires the administration of high drug doses that, in turn, can lead to polymyxin toxicity. Consequently, different delivery systems have been considered for polymyxins to overcome these obstacles. In this work, we report the development of polymyxin delivery systems based on nanoparticles obtained from the self-assembly of amphiphilic random poly(l-glutamic acid-co-d-phenylalanine). These P(Glu-co-dPhe) nanoparticles were characterized in terms of their size, surface charge, stability, cytotoxicity, and uptake by macrophages. The encapsulation efficiency and drug loading into P(Glu-co-dPhe) nanoparticles were determined for both polymyxin B and E. The release kinetics of polymyxins B and E from nanoformulations was studied and compared in buffer solution and human blood plasma. The release mechanisms were analyzed using a number of mathematical models. The minimal inhibitory concentrations of the nanoformulations were established and compared with those determined for the free antibiotics.

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“…The size of polymer nanoparticles observed by TEM in a dry state was about 30 ± 5 nm. Such difference between hydrodynamic diameter registered in aqueous media by DLS and diameter of nanospheres determined by TEM in a dry state is known for soft self-assembled materials [36,37]. This effect is related to the volatilization of water during the TEM grid drying before analysis.…”

Section: Resultsmentioning

confidence: 99%

“…In particular, 15% and 17% decrease in D H was established for KF1 and KF2 samples and 34% for EF1 one. The results obtained were compared to the data on biodegradation of random nanospheres based on copolymer of l -lysine and l -aminoisobutyric acid (P(Lys- co -Aib)), containing 29 mol% Aib and developed recently in our group [37]. Aib represents natural but non-coded amino acid, which sometimes is also used to improve the ability to enzymatic degradation [38].…”

Section: Resultsmentioning

confidence: 99%

Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications

et al. 2019

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The development and application of novel nanospheres based on cationic and anionic random amphiphilic polypeptides with prolonged stability were proposed. The random copolymers, e.g., poly(l-lysine-co-d-phenylalanine) (P(Lys-co-dPhe)) and poly(l-glutamic acid-co-d-phenylalanine) (P(Glu-co-dPhe)), with different amount of hydrophilic and hydrophobic monomers were synthesized. The polypeptides obtained were able to self-assemble into nanospheres. Such characteristics as size, PDI and ζ-potential of the nanospheres were determined, as well as their dependence on pH was also studied. Additionally, the investigation of their biodegradability and cytotoxicity was performed. The prolonged stability of nanospheres was achieved via introduction of d-amino acids into the polypeptide structure. The cytotoxicity of nanospheres obtained was tested using HEK-293 cells. It was proved that no cytotoxicity up to the concentration of 500 µg/mL was observed. C-peptide delivery systems were realized in two ways: (1) peptide immobilization on the surface of P(Glu-co-dPhe) nanospheres; and (2) peptide encapsulation into P(Lys-co-dPhe) systems. The immobilization capacity and the dependence of C-peptide encapsulation efficiency, as well as maximal loading capacity, on initial drug concentration was studied. The kinetic of drug release was studied at model physiological conditions. Novel formulations of a long-acting C-peptide exhibited their effect ex vivo by increasing activity of erythrocyte Na+/K+-adenosine triphosphatase.

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Amphiphilic polypeptides with prolonged enzymatic stability for the preparation of self-assembled nanobiomaterials

Abstract: Aib residue distribution in Lys/Aib polymers influences the morphology of forming nanoparticles and the rate of their enzymatic degradation.

Cited by 18 publications

References 55 publications

Controlled Block Polypeptide Composed of d-Type Amino Acids: A Therapeutics Delivery Platform to Inhibit Biofilm Formation of Drug-Resistant Bacteria

Controlled Block Polypeptide Composed of d-Type Amino Acids: A Therapeutics Delivery Platform to Inhibit Biofilm Formation of Drug-Resistant Bacteria

Polypeptide Self-Assembled Nanoparticles as Delivery Systems for Polymyxins B and E

Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications

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