The limitations of anticancer drugs, including poor tumor targeting and weak uptake
efficiency, are important factors affecting tumor therapy. According to characteristics of
the tumor microenvironment, in this study, we aimed to synthesize matrix metalloproteinase
(MMP)-responsive curcumin (Cur)-loaded nanoparticles (Cur-P-NPs) based on amphiphilic
block copolymer (MePEG-peptide-PET-PCL) with MMP-cleavable peptide (GPLGIAGQ) and
penetrating peptide (r9), modified to improve tumor targeting and cellular uptake. The
average size of Cur-P-NPs was 176.9 nm, with a zeta potential of 8.1 mV, and they showed
drug entrapment efficiency and a loading capacity of 87.07% ± 0.63% and 7.44% ± 0.16%,
respectively. Furthermore, Cur release from Cur-P-NPs was sustained for 144 h at pH 7.4,
and the release rate was accelerated under enzyme reaction condition. The MTT assay
demonstrated that free P-NPs had favorable biosafety, and the anti-proliferative activity
of Cur-P-NPs was positively correlated with Cur concentration in MCF-7 cells.
Additionally, the results of cellular uptake, in vivo pharmacokinetics, and
biodistribution showed that Cur-P-NPs had a good effect on cellular uptake and tumor
targeting, resulting in the best bioavailability in tumor therapy. Therefore, Cur-P-NPs,
as a promising drug delivery system, might lead to a new and efficient route for targeted
therapy in clinical practice.
Purpose:
Clinical applications of curcumin (Cur) have been greatly restricted due to its low solubility and poor systemic bioavailability. Three-arm amphiphilic copolymer tricarballylic acid-poly (ε-caprolactone)-methoxypolyethylene glycol (Tri-CL-mPEG) nanoparticles (NPs) were designed to improve the solubility and bioavailability of Cur. The present study adopted a microchannel system to precisely control the preparation of self-assembly polymeric NPs via liquid flow-focusing and gas displacing method.
Methods:
The amphiphilic three-arm copolymer Tri-CL-mPEG was synthesized and self-assembled into nearly spherical NPs, yielding Cur encapsulated into NP cores (Cur-NPs). The obtained NPs were evaluated for physicochemical properties, morphology, toxicity, cellular uptake by A549 cells, release in vitro, biodistribution, and pharmacokinetics in vivo.
Results:
Rapidly fabricated and isodispersed Cur-NPs prepared by this method had an average diameter of 116±3 nm and a polydispersity index of 0.197±0.008. The drug loading capacity and entrapment efficiency of Cur-NPs were 5.58±0.23% and 91.42±0.39%, respectively. In vitro release experiments showed sustained release of Cur, with cumulative release values of 40.1% and 66.1% at pH 7.4 and pH 5.0, respectively, after 10 days post-incubation. The results of cellular uptake, biodistribution, and in vivo pharmacokinetics experiments demonstrated that Cur-NPs exhibited better biocompatibility and bioavailability, while additionally enabling greater cellular uptake and prolonged circulation with possible spleen, lung, and kidney targeting effects when compared to the properties of free Cur.
Conclusion:
These results indicate that Tri-CL-mPEG NPs are promising in clinical applications as a controllable delivery system for hydrophobic drugs.
The problems of fossil-based resources and pollution caused by traditional nondegradable polymers have led to the need for biobased monomers and polyesters, presenting more environmentally friendly features. 2,5-Tetrahydrofurandimethanol (THFDM), a biobased monomer containing an aliphatic ring structure and an ether group, was introduced into the molecular chain of polybutylene succinate (PBS) as a sustainable unit to optimize its performance and improve its sustainability. The poly(butylene-co-tetrahydrofurandimethylene succinate) (PBTS) copolyesters were synthesized using a melt polycondensation method. The copolyesters exhibited relatively high intrinsic viscosity (1.03−1.71 dL/g). The T g values of PBTS copolyesters increased significantly along with the introduction of THFDM (from −32.2 to −12.9 °C). According to the investigation using WAXD (wide-angle X-ray diffraction) analysis and successive selfnucleating annealing (SSA) measurement, it was revealed that the introduction of THFDM reduced the crystallization ability of PBTS while increasing its crystal content with relatively low lamella thickness. This phenomenon was mainly attributed to the aliphatic rings, which limited the movement and regular stacking of the molecular chains. The degradation rate and toughness of the copolyesters improved due to the decrease of crystallization degree. Meanwhile, the gas barrier property of PBTS slightly decreased but remained at a relatively high level. The permeabilities of O 2 and CO 2 were lower than that of commercially available PBAT. In summary, the introduction of THFDM not only improved the biobased resources content and the sustainability of copolyesters but also improved the toughness and degradation performance without sacrificing gas barrier performance.
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