In vivo fate of unimers and micelles of a poly(ethylene glycol)-block-poly(caprolactone) copolymer in mice following intravenous administration

Biocompatible, biodegradable, and injectable hydrogels are a novel and promising approach for bone regeneration. In this study, poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone) (PCL-PEG-PCL), PCL-PEG-PCL-gelatin (Gel), PCL-PEG-PCL-Gel/nano-hydroxyapatite (nHA) injectable hydrogels were synthesized and evaluated in a mouse model of subcutaneous transplantation after 14 days. PCL-PEG-PCL-Gel and PCL-PEG-PCL-Gel/nHA hydrogels were fabricated with in situ precipitation method. Structure, intermolecular interaction, and the reaction between the PCL-PEG-PCL, Gel, and nHA were evaluated using a scanning electron microscope (SEM), Fourier-transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (H-NMR), and carbon nuclear magnetic resonance (C-NMR). Fourteen days after subcutaneous injection, the existence of an immune system reaction was investigated using Hematoxylin and Eosin (H&E) staining. Using immunofluorescence imaging, the number of CD68+ cells was determined in the periphery of the hydrogel. The CD8/CD4 lymphocyte ratio was also calculated in blood samples. We monitored the expression of CCL-2, BCL-2, IL-10, and CD31 using real-time PCR assay. The chemical evaluation revealed the successful integration of Gel and nHA to the PCL-PEG-PCL backbone. Histological examination showed the lack of inflammation at the site of injection. No toxicological effects were determined in hepatic and renal tissues. The addition of nHA to the PCL-PEG-PCL-Gel decreased biodegradation time. None of the hydrogels caused statistically significant differences in the number of CD68 cells (p > 0.05). The CD8/CD4 lymphocyte ratio remained unchanged in all groups (p > 0.05). Compared to the PCL-PEG-PCL group, the addition of nHA and Gel increased the expression of CCL-2, BCL-2, IL-10, and CD31 (p < 0.05). In conclusion, the current study showed that PCL-PEG-PCL-Gel/nHA hydrogels could be used in in vivo conditions without prominent toxic effects and inflammatory responses.

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Poly(caprolactone)–poly(ethylene glycol)–poly(caprolactone) (PCL–PEG–PCL) nanoparticles: a valuable and efficient system for in vitro and in vivo delivery of curcumin

RSC Advances ◽

10.1039/c5ra24942b ◽

2016 ◽

Vol 6 (17) ◽

pp. 14403-14415 ◽

Cited By ~ 29

Author(s):

Hamidreza Kheiri Manjili ◽

Ali Sharafi ◽

Hossein Danafar ◽

Mirjamal Hosseini ◽

Ali Ramazani ◽

...

Keyword(s):

Ethylene Glycol ◽

Single Step ◽

Precipitation Method ◽

Poly Ethylene Glycol ◽

Efficient System ◽

Poly Ethylene ◽

Poly Caprolactone ◽

In Vivo Delivery

Curcumin was encapsulated within PCL–PEG–PCL micelles through a single-step nano-precipitation method, leading to the creation of CUR/PCL–PEG–PCL micelles..

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Poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) Amphiphilic Copolymers for Long-Acting Injectables: Synthesis, Non-Acylating Performance and In Vivo Degradation

Molecules ◽

10.3390/molecules26051438 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1438

Author(s):

Silvio Curia ◽

Feifei Ng ◽

Marie-Emérentienne Cagnon ◽

Victor Nicoulin ◽

Adolfo Lopez-Noriega

Keyword(s):

Ethylene Glycol ◽

Ring Opening ◽

Gel Chromatography ◽

Amphiphilic Copolymers ◽

Trimethylene Carbonate ◽

Poly Ethylene Glycol ◽

Poly Ethylene ◽

Long Acting ◽

In Vivo Degradation

This article presents the evaluation of diblock and triblock poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) amphiphilic copolymers (PEG-PTMCs) as excipients for the formulation of long-acting injectables (LAIs). Copolymers were successfully synthesised through bulk ring-opening polymerisation. The concomitant formation of PTMC homopolymer could not be avoided irrespective of the catalyst amount, but the by-product could easily be removed by gel chromatography. Pure PEG-PTMCs undergo faster erosion in vivo than their corresponding homopolymer. Furthermore, these copolymers show outstanding stability compared to their polyester analogues when formulated with amine-containing reactive drugs, which makes them particularly suitable as LAIs for the sustained release of drugs susceptible to acylation.

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Local Toxicity of Topically Administrated Thermoresponsive Systems: In Vitro Studies with In Vivo Correlation

Toxicologic Pathology ◽

10.1177/0192623318810199 ◽

2018 ◽

Vol 47 (3) ◽

pp. 426-432 ◽

Cited By ~ 3

Author(s):

Sivan Yogev ◽

Ayelet Shabtay-Orbach ◽

Abraham Nyska ◽

Boaz Mizrahi

Keyword(s):

Block Copolymer ◽

Ethylene Glycol ◽

Medical Devices ◽

Poly Lactic Acid ◽

Poly Ethylene Glycol ◽

Thermoresponsive Polymers ◽

Wide Range ◽

Poly Ethylene

Thermoresponsive materials have the ability to respond to a small change in temperature—a property that makes them useful in a wide range of applications and medical devices. Although very promising, there is only little conclusive data about the cytotoxicity and tissue toxicity of these materials. This work studied the biocompatibility of three Food and Drug Administration approved thermoresponsive polymers: poly( N-isopropyl acrylamide), poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) tri-block copolymer, and poly(lactic acid-co-glycolic acid) and poly(ethylene glycol) tri-block copolymer. Fibroblast NIH 3T3 and HaCaT keratinocyte cells were used for the cytotoxicity testing and a mouse model for the in vivo evaluation. In vivo results generally showed similar trends as the results seen in vitro, with all tested materials presenting a satisfactory biocompatibility in vivo. pNIPAM, however, showed the highest toxicity both in vitro and in vivo, which was explained by the release of harmful monomers and impurities. More data focusing on the biocompatibility of novel thermoresponsive biomaterials will facilitate the use of existing and future medical devices.

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