Enhanced antitumor efficacy in colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perfluorocarbon

Wu, Pingping; Zhou, Qing; Zhu, Huayun; Zhuang, Yan; Bao, Jun

doi:10.1186/s12885-020-06803-7

Cited by 59 publications

(31 citation statements)

References 29 publications

(29 reference statements)

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“…PLGA copolymers were approved by the FDA for numerous applications, including controlled-release NPs for colon targeting. 17 It has been proven that the time required for the degradation of PLGA is associated to the ratio of monomers used in its production, ie, controlling the degradation rate can be achieved by adjusting the ratio of DL-lactide to glycolide in the copolymer. 18 EL30D55 and ES100 are proven to be biocompatible enteric polymers for oral formulations.…”

Section: Introductionmentioning

confidence: 99%

Dual Functional Eudragit® S100/L30D-55 and PLGA Colon-Targeted Nanoparticles of Iridoid Glycoside for Improved Treatment of Induced Ulcerative Colitis

Gao¹,

Yu²,

Zhang³

et al. 2021

IJN

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Aim Iridoid glycosides (IG) as the major active fraction of Syringa oblata Lindl. has a proven anti-inflammatory effect for ulcerative colitis (UC). However, its current commercial formulations are hampered by low bioavailability and unable to reach inflamed colon. To overcome the limitation, dual functional IG-loaded nanoparticles (DFNPs) were prepared to increase the residence time of IG in colon. The protective mechanism of DFNPs on DSS-induced colonic injury was evaluated in rats. Materials and Methods We prepared DFNPs using the oil-in-water emulsion method. PLGA was selected as sustained-release polymer, and ES100 and EL30D-55 as pH-responsive polymers. The morphology and size distribution of NPs were measured by SEM and DLS technique. To evaluate colon targeting of DFNPs, DiR, was encapsulated as a fluorescent probe into NPs. Fluorescent distribution of NPs were investigated. The therapeutic potential and in vivo transportation of NPs in gastrointestinal tract were evaluated in a colitis model. Results SEM images and zeta data indicated the successful preparation of DFNPs. This formulation exhibited high loading capacity. Drug release results suggested DFNPs released less than 20% at the first 6 h in simulated gastric fluid (pH1.2) and simulated small intestine fluid (pH6.8). A high amount of 84.7% sustained release from NPs in simulated colonic fluid (pH7.4) was beyond 24 h. DiR-loaded NPs demonstrated a much higher colon accumulation, suggesting effective targeting due to functionalization with pH and time-dependent polymers. DFNPs could significantly ameliorate the colonic damage by reducing DAI, macroscopic score, histological damage and cell apoptosis. Our results also proved that the potent anti-inflammatory effect of DFNPs is contributed by decrease of NADPH, gene expression of COX-2 and MMP-9 and the production of TNF-α, IL-17, IL-23 and PGE2. Conclusion We confirm that DFNPs exert protective effects through inhibiting the inflammatory response, which could be developed as a potential colon-targeted system.

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Section: Introductionmentioning

confidence: 99%

Dual Functional Eudragit® S100/L30D-55 and PLGA Colon-Targeted Nanoparticles of Iridoid Glycoside for Improved Treatment of Induced Ulcerative Colitis

Gao¹,

Yu²,

Zhang³

et al. 2021

IJN

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“…Therefore, the antitumor effects of 5FU could be improved including proliferation suppression and apoptosis [ 40 ]. An in vitro study showed there was a burst release of 17.22% of FU at 7 h and furthermore, there was a controlled release up to 78.23% for 24 h. The nanoparticles exhibited a biphasic drug release pattern with initial accelerated release followed by sustained release over seven days [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Chemopreventive Effect of 5-Flurouracil Polymeric Hybrid PLGA-Lecithin Nanoparticles against Colon Dysplasia Model in Mice and Impact on p53 Apoptosis

et al. 2021

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The use of 5-fluorouracil (5FU) is associated with multifaceted challenges and poor pharmacokinetics. Poly(lactic-co-glycolic acid)-lipid hybrid nanoparticles (PLNs)-based therapy has received attention as efficient carriers for a diversity of drugs. This study evaluated the in vivo chemotherapeutic and anti-proliferative efficacy of 5FU-loaded PLNs against 1,2-dimethylhydrazine (Di-MH) prompted colon dysplasia in mice compared to free 5FU. 5FU PLNs were prepared. Male Swiss albino mice were distributed to six experimental groups. Group 1: Saline group. All the other groups were injected weekly with Di-MH [20 mg/kg, s.c.]. Group 2: Di-MH induced colon dysplasia control group. Groups 3 and 4: Di-MH + free 5FU treated group [2.5 and 5 mg/kg]. Groups 5 and 6: Di-MH + 5FU-PLNs treated group [2.5 and 5 mg/kg]. Free 5FU and 5FU-PLNs doses were administered orally, twice weekly. Treatment with 5FU-PLNs induced a higher cytoprotective effect compared to free 5FU as indicated by lower mucosal histopathologic score and reduction in number of Ki-67 immunpositive proliferating nuclei. Additionally, there was significant upregulation of p53 and caspase 3 genes in colon specimens. Our results support the validity of utilizing the PLNs technique to improve the chemopreventive action of 5FU in treating colon cancer.

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“…The use of perfluorocarbon as an artificial oxygen carrier to improve tumor oxygenation could act synergistically with 5-FU delivery, enhancing its cytotoxic effects. Indeed, perfluorocarbon presented an additive antitumor effect for 5-FU, as the most drastic in vivo antitumor effect was observed in the case of EGF-PLGA-5-FU-PFC administration [ 181 ].…”

Section: Organic Nanosized Drug-delivery Systems For Crc Therapymentioning

confidence: 99%

Current Landscape in Organic Nanosized Materials Advances for Improved Management of Colorectal Cancer Patients

et al. 2021

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Globally, colorectal cancer (CRC) ranks as one of the most prevalent types of cancers at the moment, being the second cause of cancer-related deaths. The CRC chemotherapy backbone is represented by 5-fluorouracil, oxaliplatin, irinotecan, and their combinations, but their administration presents several serious disadvantages, such as poor bioavailability, lack of tumor specificity, and susceptibility to multidrug resistance. To address these limitations, nanomedicine has arisen as a powerful tool to improve current chemotherapy since nanosized carriers hold great promise in improving the stability and solubility of the drug payload and enhancing the active concentration of the drug that reaches the tumor tissue, increasing, therefore, the safety and efficacy of the treatment. In this context, the present review offers an overview of the most recent advances in the development of nanosized drug-delivery systems as smart therapeutic tools in CRC management and highlights the emerging need for improving the existing in vitro cancer models to reduce animal testing and increase the success of nanomedicine in clinical trials.

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Enhanced antitumor efficacy in colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perfluorocarbon

Cited by 59 publications

References 29 publications

Dual Functional Eudragit® S100/L30D-55 and PLGA Colon-Targeted Nanoparticles of Iridoid Glycoside for Improved Treatment of Induced Ulcerative Colitis

Dual Functional Eudragit® S100/L30D-55 and PLGA Colon-Targeted Nanoparticles of Iridoid Glycoside for Improved Treatment of Induced Ulcerative Colitis

Chemopreventive Effect of 5-Flurouracil Polymeric Hybrid PLGA-Lecithin Nanoparticles against Colon Dysplasia Model in Mice and Impact on p53 Apoptosis

Current Landscape in Organic Nanosized Materials Advances for Improved Management of Colorectal Cancer Patients

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