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Poly(Ethylene Glycol) Crosslinked Multi-Armed Poly(l-Lysine) with Encapsulating Capacity and Antimicrobial Activity for the Potential Treatment of Infection-Involved Multifactorial Diseases

1
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China
2
College of Pharmacy, Jinan University, Guangzhou 510632, China
3
Department of chemistry, Shantou University Medical College, Shantou 515041, China
*
Authors to whom correspondence should be addressed.
Pharmaceutics 2020, 12(1), 47; https://doi.org/10.3390/pharmaceutics12010047
Received: 17 November 2019 / Revised: 23 December 2019 / Accepted: 3 January 2020 / Published: 6 January 2020
With the development of modern medical technology, common diseases usually can be treated by traditional medicines and their formulation, while diseases with multiple etiologies still remain a great challenge in clinic. Nanoformulation was widely explored to address this problem. However, due to limited drug loading space of nanocarriers, co-delivery strategy usually fails to achieve sufficient loading of multiple drugs simultaneously. In this research, we explored the potential of poly(ethylene glycol) (PEG) crosslinked alternating copolymers MPLL-alt-PEG as both an anionic drug carrier and antimicrobial agent. The high cationic charge density of multi-armed poly(l-lysine) (MPLL) segments in MPLL-alt-PEG could endow the electrostatic encapsulation of anionic model drugs through the formation of polyion complex micelles with a MPLL/drug complex core and crosslinked PEG outer shell, enabling pH-sensitive drug release. Meanwhile, the MPLL-alt-PEG copolymer exhibits a broad spectrum of antimicrobial activities against various clinically relevant microorganisms with low hemolytic activity. Studies on antibacterial mechanism revealed that MPLL-alt-PEG attacked bacteria through the membrane disruption mechanism which is similar to that of typical antimicrobial peptides. Taken together, the present study shed light on the possibility of endowing a polymeric carrier with therapeutic effect and thus offered a promising strategy for achieving a comprehensive treatment of bacterial infection-involved multifactorial diseases. View Full-Text
Keywords: polyion complex micelles; shell crosslinked micelles; drug delivery systems; antimicrobial polymer; multifactorial diseases polyion complex micelles; shell crosslinked micelles; drug delivery systems; antimicrobial polymer; multifactorial diseases
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MDPI and ACS Style

Lu, C.; Wen, T.; Zheng, M.; Liu, D.; Quan, G.; Pan, X.; Wu, C. Poly(Ethylene Glycol) Crosslinked Multi-Armed Poly(l-Lysine) with Encapsulating Capacity and Antimicrobial Activity for the Potential Treatment of Infection-Involved Multifactorial Diseases. Pharmaceutics 2020, 12, 47.

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