Co-delivery Of Curcumin Research Articles

Co-Delivery Using pH-Sensitive Liposomes to Pancreatic Cancer Cells: the Effects of Curcumin on Cellular Concentration and Pharmacokinetics of Gemcitabine.

PEGylated pH-sensitive liposomes (PSL) dual-loaded with gemcitabine and curcumin were investigated for the potential application in gemcitabine-resistant pancreatic ductal adenocarcinoma (PDAC) treatment. Curcumin was employed as an inhibitor of the efflux transporter, multidrug resistance protein 5 (MRP5) in PDAC cells. Liposomes were prepared with gemcitabine in the core and curcumin in the bilayers. The effects of curcumin on pH-sensitivity and 'endosome escape' of PSL with different PEGylation were investigated using a calcein self-quench assay. The effects of curcumin on intracellular gemcitabine concentrations, and cytotoxicity to a MIA PaCa-2 PDAC cell line was evaluated. The pharmacokinetics were investigated in rats following intravenous injection. The addition of curcumin to the PSL bilayers (0.2-1mol%)slightly decreased the pH-sensitivity of PSL, but to a less extent than PEGylation (0-5mol%). Co-treatment with curcumin increased gemcitabine cellular accumulation in a concentration-dependent manner, and resulted in synergistic cytotoxicity towards MIA PaCa-2cells.Both these effects were augmented by the use of PSL, particularly when the two drugs were co-loaded in PSL. In rats, the dual-drug loaded PSL produced significantly reduced (p < 0.05) plasma clearance (CL) and volume of distribution (Vd) for both drugs, alongside 3 to 4-fold increases in the area-under-the-concentration-time curves compared to the free drugs. Additionally, curcumin slightly increase the plasma concentrations of gemcitabine possibly also via the MRP5 inhibition effect. Co-delivery of curcumin with gemcitabine using PSL not only increased the intracellular gemcitabine concentration thus cytotoxicity to MIA PaCa-2 cells but also significantly improved the pharmacokinetic profiles for both drugs. Graphical Abstract.

Co-delivery of curcumin and miRNA-144-3p using heart-targeted extracellular vesicles enhances the therapeutic efficacy for myocardial infarction

Curcumin exerts therapeutic effects in heart disease, but has limited bioavailability. Extracellular vesicles (EVs) have gained attention as nanovehicles; however, the poor targeting ability of systemically administered EVs still remains a crucial issue. Herein, we generated heart-targeted EVs (CTP-EVs) by functionalizing EVs surface with cardiac targeting peptide (CTP) using genetic modification of EVs-secreting cells, and further loaded curcumin into CTP-EVs (CTP-EVs-Cur). Consequently, CTP-EVs were able to specifically deliver curcumin to the heart. In addition, curcumin-loaded CTP-EVs possess improved bioavailability, and are fully functional with a high cardioprotective efficiency. Moreover, we loaded miR-144-3p in CTP-EVs-Cur following validation of miR-144-3p as a major contributor in curcumin-mediated therapeutic effects. The simultaneous packing of curcumin and miR-144-3p in CTP-EVs not only retains the active heart-targeting ability but also achieves enhanced cardioprotective effects both in vitro and in vivo, indicating the possibility of combining and sustaining their therapeutic potential by simultaneously loading in CTP-EVs. Therefore, CTP-EVs could be a potential and effective strategy for the delivery of therapeutic molecules, thereby providing a promising nanomedicine for MI therapy.

Co-delivery of curcumin and Bcl-2 siRNA by PAMAM dendrimers for enhancement of the therapeutic efficacy in HeLa cancer cells

Co-delivery of therapeutic agents and small interfering RNA (siRNA) can be achieved by a suitable nanovehicle. In this work, the solubility and bioavailability of curcumin (Cur) were enhanced by entrapment in a polyamidoamine (PAMAM) dendrimer, and a polyplex was formed by grafting Bcl-2 siRNA onto the surface amine groups to produce PAMAM-Cur/Bcl-2 siRNA nanoparticles (NPs). The synthesized polyplex NPs had a particle size of ∼180 nm, and high Cur loading content of ∼82 wt%. Moreover, the PAMAM-Cur/Bcl-2 siRNA NPs showed more effective cellular uptake, and higher inhibition of tumor cell proliferation compared to PAMAM-Cur nanoformulation and free Cur, due to the combined effect of co-delivery of Cur and Bcl-2 siRNA. The newly described PAMAM-Cur/Bcl-2 siRNA polyplex NPs could be a promising co-delivery nanovehicle.

Co-Delivery of Curcumin and Paclitaxel by "Core-Shell" Targeting Amphiphilic Copolymer to Reverse Resistance in the Treatment of Ovarian Cancer.

BackgroundOvarian cancer is a common malignancy in the female reproductive system with a high mortality rate. The most important reason is multidrug resistance (MDR) of cancer chemotherapy. To reduce side effects, reverse resistance and improve efficacy for the treatment of ovarian cancer, a “core-shell” polymeric nanoparticle-mediated curcumin and paclitaxel co-delivery platform was designed.MethodsNuclear magnetic resonance confirmed the successful grafting of polyethylenimine (PEI) and stearic acid (SA) (PEI-SA), which is designed as a mother core for transport carrier. Then, PEI-SA was modified with hyaluronic acid (HA) and physicochemical properties were examined. To understand the regulatory mechanism of resistance and measure the anti-tumor efficacy of the treatments, cytotoxicity assay, cellular uptake, P-glycoprotein (P-gp) expression and migration experiment of ovarian cancer cells were performed. In addition, adverse reactions of nanoformulation to the reproductive system were examined.ResultsHA-modified drug-loaded PEI-SA had a narrow size of about 189 nm in diameters, and the particle size was suitable for endocytosis. The nanocarrier could target specifically to CD44 receptor on the ovarian cancer cell membrane. Co-delivery of curcumin and paclitaxel by the nanocarriers exerts synergistic anti-ovarian cancer effects on chemosensitive human ovarian cancer cells (SKOV3) and multi-drug resistant variant (SKOV3-TR30) in vitro, and it also shows a good anti-tumor effect in ovarian tumor-bearing nude mice. The mechanism of reversing drug resistance may be that the nanoparticles inhibit the efflux of P-gp, inhibit the migration of tumor cells, and curcumin synergistically reverses the resistance of PTX to increase antitumor activity. It is worth noting that the treatment did not cause significant toxicity to the uterus and ovaries with the observation of macroscopic and microscopic.ConclusionThis special structure of targeting nanoparticles co-delivery with the curcumin and paclitaxel can increase the anti-tumor efficacy without increasing the adverse reactions as a promising strategy for therapy ovarian cancer.

The effect of nanomicelle curcumin, sorafenib, and combination of the two on the cyclin D1 gene expression of the hepatocellular carcinoma cell line (HUH7).

Objective(s):Hepatocellular carcinoma (HCC) is one of the most significant health condition around the world. As the only curative therapies, liver transplantation and surgical resection are the clinical treatments of HCC. Due to the systemic toxicity and severe side effects of these treatments, it is vital to establish new therapeutic approaches. The present study aimed to compare cyclin D1 (CCN D1) gene expression in hepatocellular carcinoma cell line (HUH7) when it is treated with nanomicelle curcumin and sorafenib. The purpose was to identify toxicity risk and antioxidant activity of these drugs.Materials and Methods:The toxic dose (IC50) of nanomicelle curcumin and sorafenib were detected after treatment of HUH7 cell lines with different dose of mentioned agents followed by MTT assay. CCN D1 gene expression was evaluated using real-time PCR. Following the Tukey’s multiple comparison tests, statistical analysis is done through Student’s t-test or ANOVA.Results:The expression of the CCN D1 gene was statistically significant (P<0.001) at 289.31, 128 and 152.36 for sorafenib, nanomicelle curcumin and SNC (sorafenib-nanomicelle curcumin) respectively. The finding of this study revealed that, in comparison to sorafenib alone, the treatment of HUH7 with a nanomicelle curcumin IC50 dose, in combination with sorafenib, might down-regulate CCN D1 gene expression.Conclusion:The present research indicates that the treatment of the cell line with only nanomicelle curcumin results in the down-regulation of cyclin D1. To further decrease cyclin D1 expression, the co-delivery of curcumin and sorafenib appears to induce the apoptotic process. As a result, the effect of sorafenib cytotoxicity and CCN D1 gene expression decreases twofold.

Methotrexate and Curcumin co-encapsulated PLGA nanoparticles as a potential breast cancer therapeutic system: In vitro and in vivo evaluation

Nanoparticulate delivery systems have been noticed for chemotherapeutical delivery due to their ability in controlling the drug release and reducing the side effect. These systems could also be used to deliver two drugs or more simultaneously, inhibiting the development of resistant cancerous cells. Methotrexate (MTX), one of the most frequently used chemotherapeutic agent, and Curcumin (CUR), a natural chemopreventive compound, have shown promising results in treatment or controlling the progression of cancer. The aim of this study is to prepare and evaluate polymeric nanoparticles for co-delivery of MTX and CUR. The PLGA nanoparticles were prepared and characterized in respect of their particles size, morphology, drug encapsulation efficiencies, release patterns, cell cytotoxicity, and in vivo efficacy. Altering MTX and CUR amounts leads to particle size of 142.3 ± 4.07 nm with MTX encapsulation efficiency of 71.32 ± 7.8% and CUR encapsulation efficiency of 85.64 ± 6.3%. These particles showed significantly higher cytotoxicity in comparison with free MTX or CUR or even their solo-loaded formulations. The in vivo results showed the synergic effect of MTX and CUR co-delivery on inhibiting the progression of breast cancer. Considering the appropriate in vitro properties of acquired nanoparticles for controlled drug delivery and the satisfactory in vivo efficacy results, it seems that the prepared formulation is a promising candidate for further in vivo studies.

Co-delivery of curcumin and piperine in zein-carrageenan core-shell nanoparticles: Formation, structure, stability and in vitro gastrointestinal digestion

Core-shell biopolymer nanoparticles were fabricated using a hydrophobic protein (zein) as the core and a hydrophilic anionic polysaccharide (ι-carrageenan) as the shell. The outer layer was physically cross-linked using cationic calcium ions to form salt bridges between the anionic carrageenan molecules. The potential of using these core-shell nanoparticles to co-deliver two important nutraceuticals (curcumin and piperine) was also investigated. A combination of electrostatic attraction, hydrogen bonding, and hydrophobic interactions was shown to be responsible for the assembly of the curcumin-piperine-loaded nanoparticles. Low levels of calcium ions (0–2 mM) led to the formation of small nanoparticles with compact structures, whereas higher levels (2–5 mM) promoted particle aggregation. The structural organization and morphology of the core-shell nanoparticles also depended on calcium levels, as seen by changes in circular dichroism, fluorescence spectroscopy, and electron microscopy. The core-shell nanoparticles were shown to be effective at retarding the photo- and thermal-degradation of the encapsulated curcumin and piperine. In addition, the core-shell nanoparticles could delay the release of the nutraceuticals under in-vitro gastrointestinal conditions, which may improve their oral bioavailability. In summary, core-shell nanoparticles assembled from zein and ι-carrageenan may be effective co-delivery systems for curcumin and piperine.

Codelivery of Hydrophobic and Hydrophilic Drugs by Graphene-Decorated Magnetic Dendrimers.

In this study, a nanocarrier was prepared for the codelivery of a hydrophilic drug (doxorubicin) and a hydrophobic drug (curcumin) to cancer cells. In this nanocarrier, the edges of graphene oxide sheets were decorated with a magnetic-functionalized polyamidoamine dendrimer with hydrazone groups at the end of the polymer. The edge functionalization of graphene sheets not only improved the solubility and dispersibility of graphene sheets but also imparted the magnetic properties to the nanocarrier. The resulting nanocarrier was loaded with doxorubicin through the covalent linkage and curcumin through π-π stacking. The nanocarrier showed a pH-sensitive release for both drugs, and the drug release behavior was also improved by the coimmobilization of both drugs. The cytotoxicity assay of nanocarrier showed low toxicity toward MCF-7 cell compared to unmodified graphene oxide, which was attributed to the presence of a magnetic dendrimer. Besides, the drug-loaded nanocarrier was highly toxic for cells even more than for free drugs. The cellular uptake images revealed higher drug internalization for coloaded nanocarrier than for the nanocarrier loaded with one drug alone. All of the results showed that the codelivery of curcumin and doxorubicin in the presence of the nanocarrier was more effective in chemotherapy than the nanocarrier loaded with one drug.

Co-delivery of curcumin and doxorubicin in PEGylated liposomes favored the antineoplastic C26 murine colon carcinoma microenvironment.

Our recent studies have demonstrated that the antitumor efficacy of doxorubicin (DOX), administered in long-circulating liposomes (LCL), could be considerably improved after its co-encapsulation with curcumin (CURC). Thus, the question addressed within this article is whether LCL-CURC-DOX can be exploited more efficiently than liposomal DOX for future colorectal cancer therapy. Therefore, we investigated the physicochemical and biological properties of LCL-CURC-DOX and the mechanisms of its antitumor activity in C26 murine colon carcinoma in vivo. Our results proved that the developed nanoformulation based on the co-encapsulation of CURC and DOX met the requirements of a modern drug delivery system for future cancer therapy, demonstrating enhanced antitumor activity on C26 colon carcinoma in vivo. The antitumor efficacy of LCL-CURC-DOX relied on suppressive effects on main protumor processes such as angiogenesis, inflammation, oxidative stress, invasion and resistance to apoptosis, and on the dysregulation of Th1/Th2 cell axis which favored the antineoplastic phenotype of cells in tumor microenvironment (TME). The development of multitargeted strategies aiming at stimulating antitumor effects within the tumor milieu and counteracting the escape mechanisms of cancer cells would be beneficial in the management of colon cancer in the future.

Dual-Targeting Nanoparticles: Codelivery of Curcumin and 5-Fluorouracil for Synergistic Treatment of Hepatocarcinoma

Chemotherapy has been the standard for cancer therapy, but the nonspecific cytotoxicity of chemotherapeutic agents and drug resistance of tumor cells has limited its efficacy. However, multidrug combination therapy and targeting therapy have resulted in enhanced anticancer effects and have become increasingly important strategies in clinical applications. In this study, a biotin-/lactobionic acid–modified poly(ethylene glycol)-poly(lactic-co-glycolic acid)-poly(ethylene glycol) (BLPP) copolymer was synthesized, and curcumin- and 5-fluorouracil-loaded nanoparticles (BLPPNPs/C + F) were prepared to enhance the treatment of hepatocellular carcinoma. Blank BLPPNPs were shown to have great biocompatibility via both in vitro and in vivo studies. Good targeting of tumor cells of BLPPNPs was confirmed by flow cytometry, fluorescence microscopy, and biodistribution. The synergistic anticancer effects of BLPPNPs/C + F were demonstrated by cytotoxicity and animal studies, while western blotting was used to further verify the synergistic effect of curcumin and 5-fluorouracil. The dual-targeting and drug-loaded codelivery nanosystem demonstrated higher cellular uptake and stronger cytotoxicity for tumor cells. Therefore, these dual-targeting NPs are a promising codelivery carrier that could be made available for cellular targeting of anticancer drugs to achieve better intracellular delivery and synergistic anticancer efficacy.

Co-delivery of curcumin and serratiopeptidase in HeLa and MCF-7 cells through nanoparticles show improved anti-cancer activity

Curcumin was employed to prepare anticancer nanoparticles (size 175 ± 15 nm) using anti-inflammatory enzyme serratiopeptidase by desolvation method. Here serratiopeptidase acted as a carrier as well as bioactive molecule in the nanoformulations. The Cur-SPD NPs (curcumin loaded serratiopeptidase nanoparticles) were characterized using DLS, FESEM and FTIR. The in vitro release behavior depicted biphasic pattern at 37 °C (pH 7.4) and release of 95% of both molecules occurred in 24 h. Serratiopeptidase not only provided stability to curcumin but also increased its effectiveness against cancer cells. These nanoparticles had anti-cancer activity in MCF-7 and HeLa cell lines as shown by cytotoxicity assay, DAPI nuclear staining, ROS production and DNA damage. The immunomodulatory tests showed that Cur-SPD NPs reduce level of IL-6 but increase TNFα level in THP1 cell lines. Structural similarity of serratiopeptidase to matrix metallo proteases (MMPs), particularly MMP8, have been found (based on low RMSD values) to induce TNFα production and play tumour suppressive role in certain cancers. Thus anti-cancer properties of Cur-SPD NPs may be attributed to synergistic effect of curcumin and serratiopeptidase. Thus results in present investigation provide an insight on role of serratiopeptidase in development of co-delivery of multifunctional nanoparticles with anti-cancer properties introduction.

Co-Delivery of Curcumin and Chrysin by Polymeric Nanoparticles Inhibit Synergistically Growth and hTERT Gene Expression in Human Colorectal Cancer Cells

ABSTRACTNanoparticle (NP)-based combinational chemotherapy has been proposed as a potent approach for improving intracellular drug concentrations and attaining synergistic effects in colorectal cancer therapy. Here, two well-known herbal substances, Curcumin (Cur) and Chrysin (Chr), were co-encapsulated in PEGylated PLGA NPs and investigated their synergistic inhibitory effect against Caco-2 cancer cells.Characterization of nanoformulated drugs was determined using DLS, FTIR, TEM, and SEM. Drug release study was performed using dialysis method. MTT and real-time PCR assays were applied to evaluate the cytotoxic effects of free and nano-encapsulated drugs on expression level of hTERT in Caco-2 cells.The results showed that free drugs and nano-formulations exhibited a dose-dependent cytotoxicity against Caco-2 cells and especially, Cur–Chr–PLGA/PEG NPs had more synergistic antiproliferative effect and significantly arrested the growth of cancer cells than the other groups (P < 0.05). Real-time PCR results revealed that Cur, Chr, and combination of Cur–Chr in free and encapsulated forms inhibited hTERT gene expression. Also, it was found that Cur–Chr–PLGA/PEG NPs than free combination forms could further decline hTERT expression in all concentration (P < 0.05).In summary, our study represents the first report of nano-combinational application of the natural herbal substances with a one-step fabricated codelivery system for effective colorectal cancer combinational chemotherapy.

A Mixed Component Supramolecular Hydrogel to Improve Mice Cardiac Function and Alleviate Ventricular Remodeling after Acute Myocardial Infarction

Myocardial infarction (MI) remains the major cause of death and disability in the world, and intramyocardial administration of biomaterials (e.g., hydrogels) along the perimeter of MI region is demonstrated as an effective way for the treatment of MI. The curcumin has anti‐inflammation, antioxidation, and antiapoptosis properties, and nitric oxide (NO) molecules are favorable for angiogenesis. This study prepares a mixed component hydrogel capable of releasing both bioactive curcumin and NO for the treatment of MI. The study shows that the combinational treatment of curcumin and NO can remarkably reduce collagen deposition, improve cardiac function, ameliorate adverse myocardium remodeling, suppress apoptosis, and hypertrophy as well as attenuate the expression of matrix metalloproteinases (MMPs) and transforming growth factor‐β1 (TGF‐β1) and upregulate the expression of silent information regulator 1 than curcumin alone, because of the synergistic action of both molecules and the angiogenesis promotion ability of NO. The results indicate that codelivery of curcumin and NO in a controllable manner by hydrogels might be considered as a promising option for treatment of cardiovascular disease.

Therapeutic potential of novel formulated forms of curcumin in the treatment of breast cancer by the targeting of cellular and physiological dysregulated pathways.

Breast cancer is among the most important causes of cancer related death in women. There is a need for novel agents for targeting key signaling pathways to either improve the efficacy of the current therapy, or reduce toxicity. There is some evidence that curcumin may have antitumor activity in breast cancer. Several clinical trials have investigated its activity in patients with breast cancer, including a recent trial in breast cancer patients receiving radiotherapy, in whom it was shown that curcumin reduced the severity of radiation dermatitis, although it is associated with low bioavailability. Several approaches have been developed to increase its absorption rate (e.g., nano crystals, liposomes, polymers, and micelles) and co-delivery of curcumin with adjuvants as well as different conjugation to enhance its bioavailability. In particular, micro-emulsions is an option for transdermal curcumin delivery, which has been reported to increase its absorption. Lipid-based nano-micelles is another approach to enhance curcumin absorption via gastrointestinal tract, while polymer-based nano-formulations (e.g., poly D, L-lactic-co-glycolic [PLGA]) allows the release of curcumin at a sustained level. This review summarizes the current data of the therapeutic potential of novel formulations of curcumin with particular emphasis on recent preclinical and clinical studies in the treatment of breast cancer.

PH-sensitive micelles for the intracellular co-delivery of curcumin and Pluronic L61 unimers for synergistic reversal effect of multidrug resistance

Pluronic L61 unimers, which are biomacromolecular modulators, and curcumin, a small-molecule modulator, were co-formulated into pH-sensitive micelles to reveal the full synergistic potential of combination drug treatments to reverse multidrug resistance (MDR). Compared to monotherapy, combined therapy significantly improved the cytotoxicity, cellular uptake and apoptotic effects of doxorubicin (DOX) against MCF-7/ADR cells. In mechanistic studies, both L61 and curcumin enhanced the cytotoxic effect by acting on mitochondrial signalling pathways. The compounds selectively accumulated in the mitochondria and disabled the mitochondria by dissipating the mitochondrial membrane potential, decreasing the ATP levels, and releasing cytochrome c, which initiated a cascade of caspase-9 and caspase-3 reactions. Furthermore, both curcumin and L61 down-regulated the expression and function of P-gp in response to drug efflux from the MCF-7/ADR cells. In the MCF-7/ADR tumour-bearing mouse model, intravenous administration of the combined therapy directly targeted the tumour, as revealed by the accumulation of DiR in the tumour site, which led to a significant inhibition of tumour growth without measurable side effects. In conclusion, co-formulation consisting of L61 and curcumin in pH-sensitive micelles induced significant synergistic effects on the reversal of MDR. Therefore, the intracellular co-delivery of various MDR modulators has great potential to reverse MDR in tumours.

Curcumin bioavailability from oil in water nano-emulsions: In vitro and in vivo study on the dimensional, compositional and interactional dependence

Although nanocarriers can enhance the bioavailability of free curcumin in the blood, a systematic study on the parameters that affect such enhancement is still missing. In this work we focused the attention on a nanocarrier represented by an oil in water nano-emulsion coated with a thiol modified chitosan and carried out a comprehensive study on the effects that parameters such as size, co-delivery of piperine and degree of chitosan modification can exert on curcumin bioavailability and quantified their impact. We obtained an unprecedented pharmacokinetic profile of curcumin with the best formulation, represented by a combination of a small nano-emulsion size (110nm), co-delivery of curcumin and piperine (weight ratio 100:1) and a high degree of chitosan thiolation (14–15%). Then, we assessed its anti-inflammatory properties after oral administration in rats at low doses (≤0.1 times the volume administered in the pharmacokinetic study). Furthermore, the proposed food grade nano-emulsions loaded with curcumin did not show any cytotoxic effect on normal fibroblasts, while they were able to promote death in colon cancer cells in agreement with the common knowledge of the selective action of curcumin.

Doxorubicin and curcumin co-delivery by lipid nanoparticles for enhanced treatment of diethylnitrosamine-induced hepatocellular carcinoma in mice

At present, the treatment of hepatocellular carcinoma (HCC) is an international problem. The delivery of a chemotherapeutic agent and chemosensitizer using nanocarriers has been suggested as a novel and promising strategy in cancer treatment. However, such studies in HCC remain very limited. In this study, we developed doxorubicin (DOX) and curcumin (Cur) co-delivery lipid nanoparticles (DOX/Cur-NPs) and examined its inhibitory effect on diethylnitrosamine (DEN)-induced HCC in mice. DOX/Cur-NPs displayed the physicochemical characterizations with uniform particle size, high encapsulation efficacy and sustained release profile. In DNE-induced HCC mice treated with DOX/Cur-NPs, we observed decreased liver damage assessed by serum ALT and AST levels, liver/body weight ratio, and histopathological analysis. Compared with DOX-loaded nanoparticles (DOX-NPs), DOX/Cur-NPs induced increased Caspase-3 and Bax/Bcl-2 ratio, and decreased C-myc, PCNA and VEGF. The results revealed the synergistic effect of DOX/Cur-NPs on the apoptosis, proliferation and angiogenesis of HCC. The mRNA levels of MDR1, bcl-2 and HIF-1α, and protein levels of P-gp, Bcl-2 and HIF-1α were decreased in DOX/Cur-NPs than those in DOX-NPs, indicating that Cur might reverse multidrug resistance (MDR) through these pathways. In HCC cells, enhanced cytotoxicity and decreased IC50 and resistant index further confirmed the synergistic effects of DOX/Cur-NPs than DOX-NPs. Our studies suggest that simultaneous delivery of DOX and Cur by DOX/Cur-NPs may be a promising treatment for HCC.

Codelivery of curcumin and doxorubicin by MPEG-PCL results in improved efficacy of systemically administered chemotherapy in mice with lung cancer

Systemic administration of chemotherapy for cancer often has toxic side effects, limiting the doses that can be used in its treatment. In this study, we developed methoxy poly(ethylene glycol)-poly(caprolactone) (MPEG-PCL) micelles loaded with curcumin and doxorubicin (Cur-Dox/MPEG-PCL) that were tolerated by recipient mice and had enhanced antitumor effects and fewer side effects. It was shown that these Cur-Dox/MPEG-PCL micelles could release curcumin and doxorubicin slowly in vitro. The long circulation time of MPEG-PCL micelles and the slow rate of release of curcumin and doxorubicin in vivo may help to maintain plasma concentrations of active drug. We also demonstrated that Cur-Dox/MPEG-PCL had improved antitumor effects both in vivo and in vitro. The mechanism by which Cur-Dox/MPEG-PCL micelles inhibit lung cancer might involve increased apoptosis of tumor cells and inhibition of tumor angiogenesis. We found advantages using Cur-Dox/MPEG-PCL micelles in the treatment of cancer, with Cur-Dox/MPEG-PCL achieving better inhibition of LL/2 lung cancer growth in vivo and in vitro. Our study indicates that Cur-Dox/MPEG-PCL micelles may be an effective treatment strategy for cancer in the future.