Cur-loaded Nanoparticles Research Articles

Effect of Curcumin-Loaded Zein/Polysaccharides Nanoparticles on Fatigue Stress Injury

In this study, we prepare core–shell nanoparticles as a delivery system for curcumin (Cur). The nanoparticles are composed of Zein and two polysaccharides, namely gum arabic (GA) and flaxseed gum (FG). Furthermore, we investigate the effect of Cur-loaded nanoparticles on fatigue stress injury using an animal fatigue stress model. Furthermore, we design a microneedle patch to enhance the delivery and sustained release of these nanoparticles. The results demonstrated that compared to the model group, all treatment groups exhibited significantly prolonged exhausted swimming and running times (P < 0.001), with the high-dose treatment group showing the longest running time. Moreover, our findings revealed that Cur-loaded nanoparticles possessed superior anti-fatigue stress activation properties compared to free Cur and Cur mixed with blank nanoparticles. Additionally, by enhancing drug penetration into the stratum corneum of the skin, our microneedle carrier greatly improved drug delivery efficiency.

Effect of curcumin nanoparticles on proliferation and migration of mouse airway smooth muscle cells and airway inflammatory infiltration.

Curcumin (CUR) possesses the capability to inhibit various inflammatory factors, exert anti-inflammatory effects, and alleviate asthma attacks; however, its hydrophobicity and instability significantly impede its clinical application. In this study, we synthesized CUR-loaded nanoparticles (CUR-NPs) and evaluated their impact on the proliferation, migration, and inflammatory infiltration of mouse airway smooth muscle cells (ASMCs), while investigating their underlying mechanisms. To achieve this objective, ASMCs were isolated from BALB/c mice and subjected to TGF-β1-induced cell proliferation and migration. Our findings demonstrate that CUR-NPs effectively regulate the release of CUR within cells with superior intracellular uptake compared to free CUR. The CCK-8 assay results indicate that the blank carrier does not exhibit any cytotoxic effects on cells, thus rendering the impact of the carrier itself negligible. The TGF-β1 group exhibited a significant increase in cell proliferation, whereas treatment with CUR-NPs significantly suppressed TGF-β1-induced cell proliferation. The findings from both the cell scratch assay and transwell assay demonstrated that TGF-β1 substantially enhanced cell migration, while CUR-NPs treatment effectively attenuated TGF-β1-induced cell migration. The Western blot analysis demonstrated a substantial increase in the expression levels of TGF-β1, p-STAT3, and CTGF in ASMCs following treatment with TGF-β1 when compared to the control group. Nevertheless, this effect was effectively counteracted upon administration of CUR-NPs. Furthermore, an asthma mouse model was successfully established and CUR-NPs were administered through tail vein injection. The serum levels of TGF-β1 and the expression levels of TGF-β1, p-STAT3, and CTGF proteins in the lung tissue of mice in the model group exhibited significant increases compared to those in the control group. However, CUR-NPs treatment effectively attenuated this change. Our research findings suggest that CUR-NPs possess inhibitory effects on ASMC proliferation, migration, and inflammatory infiltration by suppressing activation of the TGF-β1/p-STAT3/CTGF signaling pathway, thereby facilitating inhibition of airway remodeling.

Combination of nanoparticles and gelatin-genipin hydrogel enhances the antioxidant activity, stability, and release properties of curcumin

This study investigated the effects of nanoencapsulation and gel incorporation on the antioxidant activity, stability, and in vitro release profile of curcumin (CUR). CUR-loaded nanoparticles (CUR NPs) and CUR NPs-filled gelatin (GL)-genipin (GP) gels (GL/GP-CUR NPs) were prepared by ionic gelation and gelation, respectively. CUR NPs and GL/GP-CUR NPs exhibited significantly higher antioxidant activity, stability and in vitro release profile than free CUR (p < 0.05); however, there were distinct differences between them. GL/GP-CUR NPs demonstrated 1.17 times higher antioxidant activity than CUR NPs. The stability of GL/GP-CUR NPs was increased by 174% compared with that of CUR NPs. The in vitro release rate of CUR within CUR NPs was dramatically higher than GL/GP-CUR NPs, indicating that GL/GP gel could protect CUR NPs from the degradation (p < 0.05). This study demonstrated the potential of GL/GP-CUR NPs as an effective delivery system for enhancing the application of CUR in the food industry.

Evaluation of photodynamic therapy on nanoparticles and films loaded-nanoparticles based on chitosan/alginate for curcumin delivery in oral biofilms

Nanoparticles and nanoparticle-loaded films based on chitosan/sodium alginate with curcumin (CUR) are promising strategies to improve the efficacy of antimicrobial photodynamic therapy (aPDT) for the treatment of oral biofilms. This work aimed to develop and evaluate the nanoparticles based on chitosan and sodium alginate encapsulated with CUR dispersed in polymeric films associated with aPDT in oral biofilms. The NPs were obtained by polyelectrolytic complexation, and the films were prepared by solvent evaporation. The photodynamic effect was evaluated by counting Colony Forming Units (CFU/mL). Both systems showed adequate characterization parameters for CUR release. Nanoparticles controlled the release of CUR for a longer period than the nanoparticle-loaded films in simulated saliva media. Control and CUR-loaded nanoparticles showed a significant reduction of 3 log10 CFU/mL against S. mutans biofilms, compared to treatment without light. However, biofilms of S. mutans showed no photoinactivation effect using films loaded with nanoparticles even in the presence of light. These results demonstrate the potential of chitosan/sodium alginate nanoparticles associated with aPDT as carriers for the oral delivery of CUR, offering new possibilities to improve the treatment of dental caries and infections. This work will contribute to advances in the search for innovative delivery systems in dentistry.

In vitro-in vivo Correlation of Oral Biodegradable Curcumin Nanoparticles for Sustained Treatment Regimen of Diabetics

Background: Curcumin (CUR) has the potential to treat diabetes, but its low oral bioavailability makes it challenging to use in the treatment of chronic conditions. Objectives: To investigate in vitro–in vivo correlation (IVIVC) of oral biodegradable CUR nanoparticles (NPs) for sustained treatment regimen of diabetics. Materials and Methods: In this study, CUR biodegradable NPs were prepared using Box–Behnken design to optimize the concentration of polymer and process parameters. Results: The optimized formulation was prepared using the values obtained from the Box-Behenken method, 2.5 %w/v of polymer, 3 % w/v of TPP, and 2534 rpm of stirring speed and the actual response was observed 192.31±6.82 nm particle size, 84.26±2.87 % of entrapment efficiency, and 95.22±1.81 % of drug release (Q24 h) with the desirability function of 0.910 which indicated that the model is valid. In vitro release of curcumin from nanoparticles showed prolonged drug release up to 24 h. CUR-NPs administered orally were found to have longer Tmax, higher Cmax, larger AUC, and larger MRT compared to plain CUR. IVIVC model linear regression plots (R2= 0.9949) were obtained by plotting the graph with percent absorbed versus percent dissolved for CUR-NPs. IVIVCs were established for demonstrating the relationship between in vivo absorption and in vitro release. Conclusions: From the results, it can be concluded that this novel CUR-loaded NPs have potential to improve its therapeutic efficacy.

Curcumin-based nanoformulations alleviate wounds and related disorders: A comprehensive review.

Despite numerous advantages, curcumin's (CUR) low solubility and low bioavailability limit its employment as a free drug. CUR-incorporated nanoformulation enhances the bioavailability and angiogenesis, collagen deposition, fibroblast proliferation, reepithelization, collagen synthesis, neovascularization, and granulation tissue formation in different wounds. Designing nanoformulations with controlled-release properties ensure the presence of CUR in the defective area during treatment. Different nanoformulations encompassing nanofibers, nanoparticles (NPs), nanospray, nanoemulsion, nanosuspension, nanoliposome, nanovesicle, and nanomicelle were described in the present study comprehensively. Moreover, for some other systems which contain nano-CUR or CUR nanoformulations, including some nanofibers, films, composites, scaffolds, gel, and hydrogels seems the CUR-loaded NPs incorporation has better control of the sustained release, and thereby, the presence of CUR until the final stages of wound healing is more possible. Incorporating CUR-loaded chitosan NPs into nanofiber increased the release time, while 80% of CUR was released during 240 h (10 days). Therefore, this system can guarantee the presence of CUR during the entire healing period. Furthermore, porous structures such as sponges, aerogels, some hydrogels, and scaffolds disclosed promising performance. These architectures with interconnected pores can mimic the native extracellular matrix, thereby facilitating attachment and infiltration of cells at the wound site, besides maintaining a free flow of nutrients and oxygen within the three-dimensional structure essential for rapid and proper wound healing, as well as enhancing mechanical strength.

Curcumin Loaded Nanocarriers with Varying Charges Augmented with Electroporation Designed for Colon Cancer Therapy.

(1) Background: The size and surface charge are the most significant parameters of nanocarriers that determine their efficiency and potential application. The poor cell uptake of encapsulated drugs is the main limitation in anticancer treatment. The well-defined properties of nanocarriers will enable to target specific tissue and deliver an active cargo. (2) Methods: In the current study, poly(D,L -lactide) (PLA) nanocarriers loaded with curcumin (CUR) and differing surface charge were evaluated for transport efficacy in combination with electroporation (EP) in dependence on the type of cells. The obtained CUR-loaded nanoparticles with diameters ranging from 195 to 334 nm (derived from dynamic light scattering (DLS)) were characterized by atomic force microscopy (AFM) (morphology and shape) and Doppler electrophoresis (ζ-potential) as well as UV-vis spectroscopy (CUR encapsulation efficiency (about 90%) and photobleaching rate). The drug delivery properties of the obtained PLA nanocarriers enhanced by electroporation were assessed in human colon cancer cells (LoVo), excitable normal rat muscle cells (L6), and free of voltage-gated ion channels cells (CHO-K1). CLSM studies, viability, and ROS release were performed to determine the biological effects of nanocarriers. (3) Results: The highest photodynamic activity indicated anionic nanocarriers (1a) stabilized by C12(COONa)2 surfactant. Nanocarriers were cytotoxic for LoVo cells and less cytotoxic for normal cells. ROS release increased in cancer cells with the increasing electric field intensity, irradiation, and time after EP. Muscle L6 cells were less sensitive to electric pulses. (4) Conclusions: EP stimulation for CUR-PLA nanocarriers transport was considered to improve the regulated and more effective delivery of nanosystems differing in surface charge.

Hyaluronic Acid Modified Curcumin-Loaded Chitosan Nanoparticles Inhibit Chondrocyte Apoptosis to Attenuate Osteoarthritis via Upregulation of Activator Protein 1 and RUNX Family Transcription Factor 2.

Hyaluronic acid (HA) and curcumin (CUR) have been previously utilized for osteoarthritis (OA) treatment. CUR-loaded chitosan nanoparticles (CUR@CS NPs) and HA CUR@CS NPs were synthesized in our research to ascertain the synergistic impacts of HA and CUR-loaded NPs on OA treatment. CUR@CS NPs and HA CUR@CS NPs were synthesized with evaluation of their particle size, potential, PDI, encapsulation efficiency, drug loading and surface coating as well as HA binding rate. The in vitro CUR release curve and stability of HA-CUR@CS NPs were measured. Chondrocytes were isolated from the cartilages of OA patients, followed by cell uptake assay. The chondrocyte viability and apoptosis were determined. Subsequently, the knee OA model was established, followed by H&E, Safranin O/Fast green staining and micro-CT. HA CUR@CS NPs improved CUR stability and bioavailability. CUR@CS NPs and HA-CUR@CS NPs were successfully characterized and could further be internalized by chondrocytes. CUR@CS NPs promoted tBHP-induced chondrocyte viability and inhibited chondrocyte apoptosis. HA-CUR@CS NPs upregulated the AP-1 and RUNX2 transcription levels to activate Hedgehog pathway, which subsequently blocked the Notch pathway. Mechanically, HA-CUR@CS NPs sustained release and long-lasting effect and long-term retention in the joint cavity and downregulated the expression of several pro-inflammatory cytokines in vivo. HA-CUR@CS NPs exhibited superior effects in the preceding experiments than CUR@CS NPs. Altogether, HA-CUR@CS NPs may restrict inflammation and chondrocyte apoptosis in OA through upregulation of AP-1 and RUNX2.

Anticancer activity of Curcumin-Loaded Nanoparticles

Curcumin (CUR) is a natural bioactive compound with different bioactivities such as anti-cancer, anti-inflammatory, antioxidant, anti-microbial, and anti-parasitic, but the CUR exhibited low bioavailability, poor water solubility, and rapid hydrolysis. However, this review summarized the anticancer activities of CUR-loaded nanoparticles (NPs) and their ability to enhance CUR water solubility and increased loading efficiency in an in vitro and in vivo animal model.

Curcumin Nanoparticles Inhibit Liver Cancer by Inhibiting Angiogenesis

Liver cancer (LC) is a malignancy with the highest morbidity and mortality rates. Therefore, finding new and effective treatments is the key to improving patient outcomes. Curcumin (Cur) is effective in inhibiting tumor growth and inflammation, but its extremely low drug utilization rate limits its use as an optional treatment for LC. Drug-loaded nanoparticles (NPs) represent a cutting-edge medical and health technology that improves drug delivery, extends drug release period through tiny nanomolecular structures, and potentially circumvents the limitations of Cur therapy. In this study, we examined the effect of Cur-loaded nanoparticles (Cur-NPs) on LC cells to provide proof of principle for further clinical studies. We found that during Cur-NP treatment, the release period of Cur was significantly prolonged; whereas LC cell viability and HIF-1α/VEGF signaling was decreased. Thus, Cur-NPs can reduce the proliferation and invasion of LC cells and induce apoptosis by inhibiting the HIF-1α/VEGF signaling, thus achieving a positive effect on LC treatment.

CURCUMIN-BASED MULTIFUNCTIONAL NANOSYSTEMS

The use of multifunctional nanosystems in medicine and research is of contemporary interest. Aim. The purpose of the work was to summarize publications on the prospects of creating and using nanocontainers based on curcumin (Cur). Cur fluorescence in nanoparticles (NP) makes it possible to investigate the distribution of fluorescent and non-fluorescent components, significantly accelerating the study and implementation of drugs in practice. Particular attention is paid to the use of hydrophobic substances in NP, to penetrate into a living cell. Understanding the interaction of NP with living cells is extremely important when these particles are used to transport and deliver water-insoluble drugs to cells. Cur is one of the drugs with various and very promising pharmaceutical effects, it is poorly soluble in aqueous media, and the use of nanocarriers is an effective way to significantly increase its bioavailability. Cur has its own fluorescence, which enables to use it in multifunctional fluorescent nanosystems, for example, with Pluronic® micelles. The use of the fluorescence method makes it possible to trace the stages of interaction of Cur-loaded NP with cultured cells and their localization in cell organelles. With this approach, nanoscale dynamics of drug distribution and stability is observed over time. Conclusions. The main conclusion is that for unstable in the aquatic environment drugs such as Cur, it is necessary to use the most hydrophobic nanostructures without traces of water, which include the nuclei of Pluronic® micelles. This method makes it possible to use other poorly water-soluble drugs. A promising area of nanomedicine is the creation of complex bio-compatible nanomaterials based on several active drugs that reduce the toxicity of preparations to normal cells.

Novel β-cyclodextrin based copolymers: fabrication, characterization and in vitro release behavior

A novel cyclodextrin-contained copolymer poly(AAc-co-SA-AC-co-allyl-β-CD) was synthesized based on the method of redox radical polymerization. Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance (1H NMR) spectra were used to study the structure of the obtained copolymer. The molecular weight of the copolymer was studied by gel permeation chromatography (GPC). The polymeric nanoparticles (NPs) were fabricated by a solvent evaporation method. The morphology and particle size distribution of the cargo-free NPs were investigated with transmission electron microscope (TEM), atomic force microscope (AFM), and laser particle analyzer, respectively. Curcumin (Cur) was selected as a model drug and encapsulated into the above NPs. The distribution of Cur in the drug-loaded NPs was analyzed by the method of differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Moreover, the release profiles of Cur from Cur-loaded NPs were studied in pH 6.8 and 7.4 buffers. The results of FTIR and 1H NMR spectra confirmed the successful synthesis of poly(AAc-co-SA-AC-co-allyl-β-CD). GPC curve proved that the molecular weight of the copolymer was more than 60 kDa. TEM and AFM images illustrated that the cargo-free NPs were in spherical shape with a diameter about 40 nm. XRD patterns and DSC curves indicated that most of Cur distributed in the Cur-loaded NPs with amorphous state. Importantly, the medicated NPs showed sustained release characteristics toward Cur.

A Cost-Effective Nano-Sized Curcumin Delivery System with High Drug Loading Capacity Prepared via Flash Nanoprecipitation.

Flash nanoprecipitation (FNP) is an efficient technique for encapsulating drugs in particulate carriers assembled by amphiphilic polymers. In this study, a novel nanoparticular system of a model drug curcumin (CUR) based on FNP technique was developed by using cheap and commercially available amphiphilic poly(vinyl pyrrolidone) (PVP) as stabilizer and natural polymer chitosan (CS) as trapping agent. Using this strategy, high encapsulation efficiency (EE > 95%) and drug loading capacity (DLC > 40%) of CUR were achieved. The resulting CUR-loaded nanoparticles (NPs) showed a long-term stability (at least 2 months) and pH-responsive release behavior. This work offers a new strategy to prepare cost-effective drug-loaded NPs with high drug loading capacity and opens a unique opportunity for industrial scale-up.

Curcumin Nanoparticles Attenuate Lipotoxic Injury in Cardiomyocytes Through Autophagy and Endoplasmic Reticulum Stress Signaling Pathways.

Although curcumin (CUR) has many advantages, its hydrophobicity and instability limit its application. In this study, the anti-lipotoxic injury activity of CUR-loaded nanoparticles (CUR-NPs) and the corresponding mechanism were examined in palmitate (PA)-treated cardiomyocytes. An amphiphilic copolymer was selected as the vehicle material, and CUR-NPs with suitable sizes were prepared under optimized conditions. Cellular uptake was examined by confocal laser scanning microscopy, and cell proliferation inhibition rate was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra bromide (MTT) assay. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay was used to detect cell apoptosis. The protein expression was detected by western blot. Exposure to PA reduces the proliferation of cardiomyocytes, but this effect was strongly reversed by CUR-NPs. In addition, our data showed that CUR-NPs strongly inhibited cell apoptosis in PA-treated cardiomyocytes. Furthermore, CUR-NPs remarkably increased the expression of LC3-II, as well as inhibited the expression of p-PERK, p-eIF2α, and ATF4 in PA-treated cardiomyocytes. Salubrinal (an eIF2α inhibitor) blocked the protective effect of CUR-NPs against PA-induced cardiomyocyte injury. Our results suggested that CUR-NPs can activated the autophagy pathway and protect myocardial cells from apoptosis, and these effects may be mediated by the eIF2α-related endoplasmic reticulum stress signaling pathway.

Albumin-based lipoprotein nanoparticles for improved delivery and anticancer activity of curcumin for cancer treatment.

Aim: To prepare curcumin (CUR)-loaded, dioleoyl phosphoethanolamine-conjugated human serum albuminnanoparticles(NPs)and to evaluate their effectiveness in breast cancer therapy. Materials & methods: The CUR-loaded NPs were physicochemically characterizedand evaluated for their cytotoxicity in murine (4T1) and human breast cancer (MDA-MB-231) cell lines. The antitumor efficacy of the nanomedicine was evaluated in 4T1 tumor bearing mice. Results: The prepared NPs exhibited encapsulation and drug loading efficiencies of approximately 79 and 21%, respectively. The NPs were taken up efficiently and markedly hindered the proliferation of breast cancer cells compared with free drug. NPs exhibited greater suppression of tumor growth in 4T1 tumor bearing mice. Conclusion: CUR-human serum albumin-dioleoyl phosphoethanolamineNPs could be a potential treatment alternative for solid tumors, including breast cancer.

Dual chemotherapy with benznidazole at suboptimal dose plus curcumin nanoparticles mitigates Trypanosoma cruzi-elicited chronic cardiomyopathy.

Curcumin (Cur) is a natural polyphenolic flavonoid isolated from the rhizomes of Curcuma longa. Its anti-inflammatory and cardioprotective properties are increasingly considered to have beneficial effects on the progression of cardiomyopathy associated with Chagas disease, caused by Trypanosoma cruzi. However, the Cur therapeutic limitation is its bioavailability and new Cur nanomedicine formulations are developed to overcome this obstacle. In this research, we provide evidence showing that oral therapy with a suboptimal dose of the standard parasiticidal drug benznidazole (BZ) in combination with Cur-loaded nanoparticles is capable of reducing myocardial parasite load, cardiac hypertrophy, inflammation and fibrosis in mice with long-term infection by T. cruzi. Treatment with BZ plus Cur was highly effective in downregulating myocardial expression of proinflammatory cytokines/chemokines (IL-1β, TNF-α, IL-6, CCL5), and the level/activity of matrix metalloproteinases (MMP-2, MMP-9) and inducible enzymes (cyclooxygenase, nitric oxide synthase) implicated in leukocyte recruitment and cardiac remodeling. Oral administration of a Cur-based nanoformulation displays potential as a complementary strategy to the conventional BZ chemotherapy in the treatment of chronic Chagas heart disease.

Preparation and Evaluation of Collagen-Based Patches as Curcumin Carriers.

Patients with psoriasis are dissatisfied with the standard pharmacological treatments, whether systemic or topical, with many of them showing interest in complementary and alternative medicine. Curcumin (Cur), a natural polyphenol derived from turmeric, has recently gained attention for skin-related diseases because of its proven anti-inflammatory action. However, topical treatment with Cur would be inadequate because of its hydrophobicity, instability, and low bioavailability. In addition, hyperkeratosis and lack of moisture in psoriatic skin result in low penetration that would prevent actives from permeating the stratum corneum. In this work, a polymer-based formulation of Cur for the topical treatment of psoriasis is reported. To improve the physicochemical stability of Cur, it was first encapsulated in chitosan nanoparticles. The Cur-loaded nanoparticles were incorporated in a hydrophilic, biocompatible collagen-based patch. The nanoparticle-containing porous collagen patches were then chemically cross-linked. Morphology, chemical interactions, swelling ratio, enzymatic hydrolysis, and Cur release from the patches were evaluated. All patches showed excellent swelling ratio, up to ~1500%, and after cross-linking, the pore size decreased, and their hydrolysis rates decelerated. The in vitro release of Cur was sustained with an initial burst release, reaching 55% after 24 h. Cur within the scaffolds imparted a proliferation inhibitory effect on psoriatic human keratinocytes in vitro.

Odorranalectin modified PEG–PLGA/PEG–PBLG curcumin-loaded nanoparticle for intranasal administration

Curcumin (Cur) is a promising drug for neurological diseases. Nevertheless, the application of Cur has been limited due to its difficulty in penetrating blood-brain barrier (BBB). Intranasal drug delivery, a noninvasive alternative delivery of Cur, can effectively help Cur cross BBB and inert into central nervous system directly. Odorranalectin (OL) which is the smallest lectin can prolong the residence time of Cur in the nasal mucosa and promote cellular uptake. In this work, a nasal delivery system incorporating OL modified Cur-loaded nanoparticles (Cur–OL–NPs) was developed and expected to bypass BBB and promote the absorption of Cur. We conjugated OL to polyethylene glycol-poly (lactic-co-glycolic acid) (PEG–PLGA), and combined polyethylene glycol-poly (γ-benzyl-L-glutamate) (PEG–PBLG) and OL–PEG–PLGA to prepare nanoparticles to improve the stability, bioavailability and targeting of Cur. Compared with unmodified NPs, increased efficiency of Cur–OL–NPs cellular uptake by Calu-3 cells had been obtained with no severe toxicity. Furthermore, in vivo pharmacokinetic studies also showed that Cur–OL–NPs had higher relative bioavailability. Thus, it is concluded that the results indicated that OL–NPs as carriers of Cur had a promising future in nasal drug delivery system.

Preparation of Poloxamer188-b-PCL and Study on in vitro Radioprotection Activity of Curcumin-Loaded Nanoparticles.

A novel polymer of poloxamer188-b-PCL was synthesized via a ring-opening polymerization. Fourier transform infrared spectroscopy (FTIR), Raman, and 1H nuclear magnetic resonance (1H NMR) spectra were used to study the structures of obtained poloxamer188-b-PCL. The thermo-stability of poloxamer188 -b-PCL was carried out with a thermal gravimetric analyzer (TGA), and cytotoxicity was obtained using the CCK8 method. Cargo-free and curcumin (CUR)-loaded poloxamer188-b-PCL NPs were fabricated via the solvent evaporation method. The morphology, particle size distribution, and stability of cargo-free NPs were studied with a scanning electron microscope (SEM) and laser particle analyzer. The in vitro radioprotection activity of CUR-loaded NPs was performed. FTIR, Raman, and 1H NMR spectra confirmed that poloxamer188-b-PCL was obtained. TGA curves suggested poloxamer188-b-PCL had better thermo-stability than original poloxamer188. Cell tests suggested that the cargo-free NPs had no cytotoxicity. SEM image showed that the cargo-free NPs were spherical with a diameter of 100 nm. Free radical scavenging experiments proved that CUR-loaded NPs had better antioxidant activity than CUR solutions. CUR-loaded NPs could be detected in all tissues, including liver, kidneys and lung. In summary, this work demonstrated a feasibility of developing an injective formulation of CUR and provided a protection agent in caner radiotherapy.

99mTc Radiolabeled HA/TPGS-Based Curcumin-Loaded Nanoparticle for Breast Cancer Synergistic Theranostics: Design, in vitro and in vivo Evaluation.

BackgroundEmerging cancer therapy requires highly sensitive diagnosis in combination with cancer-targeting therapy. In this study, a self-assembled pH-sensitive curcumin (Cur)-loaded nanoparticle of 99mTc radiolabeled hyaluronan-cholesteryl hemisuccinate conjugates (HA-CHEMS) and D-a-tocopheryl polyethylene glycol succinate (TPGS) was prepared for breast cancer synergistic theranostics.Materials and MethodsThe synthesized amphiphilic HA-CHEMS conjugates and TPGS self-assembled into Cur-loaded nanoparticles (HA-CHEMS-Cur-TPGS NPs) in an aqueous environment. The physicochemical properties of HA-CHEMS-Cur-TPGS NPs were characterized by transmission electron microscopy (TEM) and dynamic lighter scattering (DLS). The in vitro cytotoxicity of HA-CHEMS-Cur-TPGS NPs against breast cancer cells was evaluated by using the methyl thiazolyl tetrazolium (MTT) assay. Moreover, the in vivo animal experiments of HA-CHEMS-Cur-TPGS NPs including SPECT/CT imaging biodistribution and antitumor efficiency were investigated in 4T1 tumor-bearing BALB/c mice; furthermore, pharmacokinetics were investigated in healthy mice.ResultsHA-CHEMS-Cur-TPGS NPs exhibited high curcumin loading, uniform particle size distribution, and excellent stability in vitro. In the cytotoxicity assay, HA-CHEMS-Cur-TPGS NPs showed remarkably higher cytotoxicity to 4T1 cells with an IC50 value at 38 μg/mL, compared with free curcumin (77 μg/mL). Moreover, HA-CHEMS-Cur-TPGS NPs could be effectively and stably radiolabeled with 99mTc. The SPECT images showed that 99mTc-HA-CHEMS-Cur-TPGS NPs could target the 4T1 tumor up to 4.85±0.24%ID/g at 4 h post-injection in BALB/c mice. More importantly, the in vivo antitumor efficacy studies showed that HA-CHEMS-Cur-TPGS NPs greatly inhibited the tumor growth without resulting in obvious toxicities to major organs.ConclusionThe results indicated that HA-CHEMS-Cur-TPGS NPs with stable 99mTc labeling and high curcumin-loading capacity hold great potential for breast cancer synergistic theranostics.