Influence of architecture of high molecular weight linear and branched polyglycerols on their biocompatibility and biodistribution

ul-haq, Muhammad Imran; Lai, Benjamin; Chapanian, Rafi; Kizhakkedathu, Jayachandran N.

doi:10.1016/j.biomaterials.2012.09.007

Cited by 142 publications

(172 citation statements)

References 57 publications

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“…In the case of DFO conjugates, the organ distribution is completely changed and the data look similar to the organ distribution of polymer scaffold alone [44][45][46], except in the case of ULC-65 where the drug content was higher. As given earlier, ULC-65 showed preferential liver excretion similar to unconjugated DFO [42].…”

Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 55%

In vivo efficacy, toxicity and biodistribution of ultra-long circulating desferrioxamine based polymeric iron chelator

et al. 2016

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Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 55%

In vivo efficacy, toxicity and biodistribution of ultra-long circulating desferrioxamine based polymeric iron chelator

et al. 2016

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“…HPGs are highly compact, globular and contain a large number of hydroxyl groups which are readily available for modification 40 . HPGs can easily be synthesized overnight via a one-pot anionic ring-opening polymerization ( Figure 1) with low polydispersity [51][52][53] .…”

Section: Epidermidis) Bacillus Cereus and Leuconostoc Lactismentioning

confidence: 99%

Conjugation of Aurein 2.2 to HPG Yields an Antimicrobial with Better Properties

et al. 2015

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Aurein 2.2 is an antimicrobial peptide (AMP) whose mechanism of action is quite well-understood and that has good activity against Gram-positive bacteria. It is, however, highly cytotoxic. Poly(ethylene glycol) (PEG) conjugation (PEGylation) of protein and peptide drugs has been used for decades to improve their in vivo efficacy and blood circulation by enhancing the biocompatibility of the protein or peptide in question. However, the relatively large hydrodynamic size, high intrinsic viscosity, the limited number of functional groups available for conjugation, and immunogenicity of high molecular weight PEG limits its use in bioconjugation applications. Recently, hyperbranched polyglycerol (HPG) has been gaining attention as an alternative to PEG due to its excellent biocompatibility. Here, for the first time, we report the synthesis of HPG conjugates of antimicrobial peptides. Aurein 2.2 peptide was conjugated to high molecular weight HPG with a varying number of peptides per polymer, and the biocompatibility and antimicrobial activity of the conjugates were investigated. The antimicrobial activity of the peptide and its conjugates were determined by measuring the minimal inhibitory concentration (MIC) against Staphylococcus aureus and Staphylococcus epidermidis. The interaction of aurein 2.2 peptide and the conjugates with a model bacterial biomembrane was investigated using CD spectroscopy to understand the mode of action of the conjugates. The biocompatibility of the AMP-polymer conjugates was investigated by measuring red cell lysis, platelet activation and aggregation, complement activation, blood coagulation, and cell toxicity. Our results show that the size of the conjugates and the peptide density influence the biocompatibility of the antimicrobial conjugates. These results will help to further define the properties of HPG-AMP conjugates and set the stage for development of better therapeutic agents.

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“…[15][16][17] Moreover, the ability to control the circula-68 tion half-lives and the excellent biocompatibility of HPGs make 69 them advantageous over dendrimers in drug delivery 70 applications. [18][19][20] Furthermore, because of its structural similar-71 ities to PEG, HPG possesses intrinsic ability to avoid MPS 72 uptake, yet it is thermally and oxidatively more stable than 73 PEG. 18 Hydrophobically derivatized HPG was originally 74 developed as a serum albumin substitute for use as a plasma 75 expander.…”

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Investigation of hydrophobically derivatized hyperbranched polyglycerol with PEGylated shell as a nanocarrier for systemic delivery of chemotherapeutics

Misri¹,

Wong²,

Shenoi

et al. 2015

Nanomedicine: Nanotechnology, Biology and Medicine

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Influence of architecture of high molecular weight linear and branched polyglycerols on their biocompatibility and biodistribution

Cited by 142 publications

References 57 publications

In vivo efficacy, toxicity and biodistribution of ultra-long circulating desferrioxamine based polymeric iron chelator

In vivo efficacy, toxicity and biodistribution of ultra-long circulating desferrioxamine based polymeric iron chelator

Conjugation of Aurein 2.2 to HPG Yields an Antimicrobial with Better Properties

Investigation of hydrophobically derivatized hyperbranched polyglycerol with PEGylated shell as a nanocarrier for systemic delivery of chemotherapeutics

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