Dynamic Stabilization of Unit Polyion Complexes Incorporating Small Interfering RNA by Fine-Tuning of Cationic Block Length in Two-Branched Poly(ethylene glycol)-b-poly(l-lysine)

AbstractBiodegradable films of methoxy poly(ethylene glycol)-b-poly(DL-lactideco- glycolide-co-ε-caprolactone) diblock copolymers (MPEG-b-PDLLGCL) were prepared by solution casting method. Effects of MPEG block length and DLL:G:CL ratio of the MPEG-b-PDLLGCL films on their mechanical properties and hydrolytic degradation were studied and discussed. It was found that the mechanical properties of films were strongly dependent on glass transition temperatures (Tg) of the diblock copolymers. The hydrolytic degradation was investigated in phosphatebuffered solution at 37°C. The degraded films were characterized using gravimetry (%water uptake and %weight loss), 1H-NMR spectroscopy, differential scanning calorimetry and size exclusion chromatography. The %weight loss of the degraded films increased and molecular weight decreased on increasing the MPEG block length and incorporating the G and CL units, according to their %water uptakes. The MPEG content of the degraded film decreased and the Tg increased with hydrolytic degradation time.

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Phase Fluctuation Chromatography of Diblock Copolymer of Poly(ethylene glycol) and Poly(l-lactide) for Fractionation by the Block Length Ratio

Macromolecules ◽

10.1021/ma0101207 ◽

2001 ◽

Vol 34 (14) ◽

pp. 4949-4957 ◽

Cited By ~ 4

Author(s):

Dean Lee ◽

Iwao Teraoka ◽

Tomoko Fujiwara ◽

Yoshiharu Kimura

Keyword(s):

Ethylene Glycol ◽

Diblock Copolymer ◽

Phase Fluctuation ◽

Length Ratio ◽

Block Length ◽

Poly Ethylene Glycol ◽

Poly Ethylene

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The Importance of Poly(ethylene glycol) Alternatives for Overcoming PEG Immunogenicity in Drug Delivery and Bioconjugation

Polymers ◽

10.3390/polym12020298 ◽

2020 ◽

Vol 12 (2) ◽

pp. 298 ◽

Cited By ~ 48

Author(s):

Thai Thanh Hoang Thi ◽

Emily H. Pilkington ◽

Dai Hai Nguyen ◽

Jung Seok Lee ◽

Ki Dong Park ◽

...

Keyword(s):

Drug Delivery ◽

Ethylene Glycol ◽

Blood Circulation ◽

Drug Efficacy ◽

Poly Ethylene Glycol ◽

Life Threatening ◽

Poly Ethylene ◽

Interfering Rna ◽

Accelerated Blood Clearance ◽

Established Technique

Poly(ethylene glycol) (PEG) is widely used as a gold standard in bioconjugation and nanomedicine to prolong blood circulation time and improve drug efficacy. The conjugation of PEG to proteins, peptides, oligonucleotides (DNA, small interfering RNA (siRNA), microRNA (miRNA)) and nanoparticles is a well-established technique known as PEGylation, with PEGylated products have been using in clinics for the last few decades. However, it is increasingly recognized that treating patients with PEGylated drugs can lead to the formation of antibodies that specifically recognize and bind to PEG (i.e., anti-PEG antibodies). Anti-PEG antibodies are also found in patients who have never been treated with PEGylated drugs but have consumed products containing PEG. Consequently, treating patients who have acquired anti-PEG antibodies with PEGylated drugs results in accelerated blood clearance, low drug efficacy, hypersensitivity, and, in some cases, life-threatening side effects. In this succinct review, we collate recent literature to draw the attention of polymer chemists to the issue of PEG immunogenicity in drug delivery and bioconjugation, thereby highlighting the importance of developing alternative polymers to replace PEG. Several promising yet imperfect alternatives to PEG are also discussed. To achieve asatisfactory alternative, further joint efforts of polymer chemists and scientists in related fields are urgently needed to design, synthesize and evaluate new alternatives to PEG.

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Thermal and mechanical properties of highly flexible poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) bioplastics: Effects of poly(ethylene glycol) block length and chain extender

Journal of Elastomers & Plastics ◽

10.1177/0095244319827993 ◽

2019 ◽

Vol 52 (2) ◽

pp. 142-158 ◽

Cited By ~ 1

Author(s):

Yodthong Baimark ◽

Yaowalak Srisuwan

Keyword(s):

Ethylene Glycol ◽

Chain Extender ◽

Chain Extension ◽

Block Length ◽

Melt Blending ◽

Poly Ethylene Glycol ◽

Lower Stress ◽

Practical Applications ◽

Poly Ethylene ◽

Reactive Melt

The brittleness of poly(L-lactide) (PLLA) bioplastic is the main disadvantage for practical applications. Herein, we report the synthesis of high-molecular-weight PLLA- b-poly(ethylene glycol)- b-PLLA (PLLA-PEG-PLLA) block copolymers by ring-opening polymerization of LLA. The highly flexible PLLA-PEG-PLLAs were prepared by reactive melt blending with an epoxy-based chain extender formed as long-chain branched structures. The effects of PEG block length and content of chain extender were investigated. The results showed that the chain extension reaction reduced crystallinities of the PLLA-PEG-PLLAs. All the chain-extended PLLA-PEG-PLLA films had no phase separation. The lower crystallinities of PLLA-PEG-PLLA films obtained with higher contents of chain extender enhanced the film drawability. The longer PEG block length resulted in higher strain at break and lower stress at the break of PLLA-PEG-PLLA films. These chain-extended PLLA-PEG-PLLAs have potential for use as highly flexible bioplastics.

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