Curcumin Loading Research Articles

The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders.

Curcumin is the primary polyphenol in turmeric’s curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin’s bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.

In Vitro Neuroprotective Effects of Macrophage Membrane-Derived Curcumin-Loaded Carriers against 1-Methyl-4-phenylpyridinium-Induced Neuronal Damage.

Curcumin (CUR) possesses neuroprotective effects. However, its clinical therapeutic efficacy is limited because of its low systemic bioavailability due to poor water solubility and fast metabolism. Herein, we designed biomimetic therapeutic nanovesicles (NVs) with enhanced performance and biocompatibility for the intracellular delivery of hydrophobic CUR. Cell membrane NVs were constructed to function as drug carriers by the serial extrusion of macrophages using filters with decreasing pore sizes. Various CUR loading strategies were also evaluated. Furthermore, the neuroprotective effects of the CUR-loaded NVs (NVs–CUR) against 1-methyl-4-phenylpyridinium (MPP+)-induced neuronal degeneration were studied thoroughly. CUR-loaded NVs were readily taken up by neurons in vitro, and the survival rate of MPP+-induced primary neurons increased from 65.37 ± 6.37 to 90.91 ± 3.18% after pretreatment with NVs–CUR. Compared with traditional Parkinson’s disease chemotherapeutic treatment, NV formulations can improve the bioavailability of this drug. NVs are expected to become a new and effective drug-delivery platform for further applications in the field of central nervous system therapy.

Inhaled curcumin mesoporous polydopamine nanoparticles against radiation pneumonitis

Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ-ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy 60Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.

Zeolitic imidazolate frameworks as an efficient platform for potential curcumin-based on/off fluorescent chemosensor

Incorporating the fluorescent organic compound on the platform toward the capture of metal ions has become an attractive strategy for chemical sensor. Curcumin-based sensory platforms are fabricated chemo-sensors for the detection of cations and anions. Herein, the homogenous nanoparticle porous zeolitic imidazolate frameworks, ZIF-8 and ZIF-11 with a smaller than 100 nm particle size were used as platform for curcumin loading. The ZIF compounds were characterized by powder X-ray diffraction, N 2 sorption isotherms, and thermal gravimetric analysis to assess their potential for liquid adsorption. According to investigation of liquid adsorption, the curcumin concentration, time, and temperature of adsorption process have been carried out to provide the adsorption properties and adsorption capacity of two materials. The maximum adsorption capacity on both ZIFs was up to 4.5 mg mg −1 , with faster adsorption rates than other adsorbents reported. Compared to ZIF-11, ZIF-8 surprisingly demonstrates higher encapsulation, intraparticle diffusion, and lower kinetic parameters of k 2 . This phenomenon is explained via the crystallographic aperture size, surface area, and affinity of the 2-methylimidazolate linker in ZIF-8 relative to the benzimidazole linker in ZIF-11. The release of curcumin in both pH 5.5 and 7.4 environments below 2% for 24h showed the consistent stability of curcumin in the nanocarrier. In addition, the curcumin-based sensory ZIF-8 and ZIF-11 exhibited efficient fluoride ion sensing performance with a detection limit as low as 100 ppm. The colorimetric fluorescence sensing at ON/OFF mode highlighted the promising potential of Cur-based ZIF materials for the high dose of fluoride ion in water at pH 5.5 and 7.4. • The ZIF-8 and ZIF-11 nanomaterials (<100 nm) were successfully synthesized. • The materials display highly efficient and fast curcumin adsorption. • Kinetics, thermodynamics, and adsorption mechanism were comprehensively examined. • The stronger stability of curcumin in ZIFs at PBS is lower 8% over 10 days. • The curcumin-loaded in ZIFs exhibited efficient fluoride ion sensing performance.

Effect of sodium chloride on formation and structure of whey protein isolate/hyaluronic acid complex and its ability to loading curcumin

Effects of ionic strength (0–150 mM NaCl) on formation and properties of whey protein isolate (WPI) and hyaluronic acid (HA) complexes (WPI/HA = 4:1, total concentration of 0.1%, w/w) were investigated. Subsequently, coacervates with corresponding NaCl were applied as delivery vehicle for curcumin. Turbidity analysis showed that NaCl enhanced WPI and HA complexation at 5–40 mM. Adding NaCl (0–150 mM) shifted pHφ1 and pHφ2 towards lower and higher pH values, respectively. Zeta potential measurement showed that surface charge of complexes decreased with increasing NaCl concentration. Circular dichroism and fluorescence spectra indicated that α-helix content and fluorescence intensity of WPI involved in complexation changed with increase of varied NaCl concentration. Isothermal Titration Calorimetry data and Confocal Laser Microscope analysis showed that screening effect of NaCl hindered electrostatic interaction, whereas hydrophobic force may promote complexation at NaCl concentration of 0–30 mM. Fluorescence quenching data revealed that presence of salt at low (5–40 mM) and high (50–150 mM) levels increased and decreased binding ability of WPI/HA with curcumin, respectively. Presence of salt at 5–40 mM improved particle size, encapsulation efficiency and loading capacity compared with control. Data demonstrated that critical NaCl concentration was around 40 mM and this finding could facilitate applications of WPI/HA complex as delivery vehicle of bioactive substances.

Hierarchical dual-responsive cleavable nanosystem for synergetic photodynamic/photothermal therapy against melanoma

Currently, the combining photodynamic therapy (PDT) with photothermal therapy (PTT) modalities based on a single near infrared (NIR) laser irradiation and highly selective internalization still remain a challenge. Herein, a hierarchical dual-responsive cleavable nanosystem for synergetic NIR triggered PDT/PTT is reported. The engineered nanoplatform (Au NRs/Cur/UCNPs@PBE) is designed by loading curcumin (Cur, photosensitizer) on gold nanarods (Au NRs) to build PDT/PTT therapy system, which was encapsulated outside with upconversion nanoparticles (UCNPs) and then modified with phenylboronic double ester (PBE). The pH and ROS-responsive feature made Au NRs/Cur/UCNPs@PBE provide a fundamental structural evolution and improve the specificity and intracellular accumulation to tumors. Au NRs/Cur/UCNPs@PBE exhibited significant PDT and PTT efficiency against two type melanoma cells due to upconversion nanoparticles and Au NRs induced by an 808 nm laser. Notably, the platform can mainly activate apoptosis and partial ferroptosis to achieve the synergistic PDT/PTT, furthermore, the integrated PDT with PTT using Au NRs/Cur/UCNPs@PBE showcased a great antitumor efficacy in vivo superior to the other alone treatment. Our findings highlight that this intelligent nanoagents for synergistic phototherapy facilitate enhanced fighting melanoma and provide a promising strategy for melanoma theranostics.

Sustained delivery efficiency of curcumin through ZSM-5 nanozeolites/electrospun nanofibers for counteracting senescence of human adipose-derived stem cells

In the present study, ZSM-5 nanozeolite was incorporated into the Poly-ε-Caprolactone/Gelatin nanofibers (PCL-GEL NFs) for controlled and sustained release of a natural polyphenol, curcumin (CUR) to enhance the prolonged in vitro expansion of human adipose-derived stem cells (hADSCs) without inducing cellular senescence. XRD, FTIR, BET, TGA, FE-SEM, TEM and water contact angle analysis were used to characterize the fabricated nanozeolites and NFs. A study on the drug discharge pattern from the composite CUR@ZSM-5/PCL-GEL electrospun NFs displayed that by loading CUR into the ZSM-5 nanozeolites, the initial burst release was somewhat eliminated, and a sustained and prolonged drug discharge from NFs was obtained. The data set obtained through FE-SEM, LSCM, MTT and PicoGreen assays, qPCR, and western blotting also revealed better cell adhesion and enhanced metabolic activity and proliferation rate for hADSCs cultured on the CUR@ZSM-5/PCL-GEL NFs compared to other types of NFs after 14 and 28 days of incubation. Besides, Utilizing ZSM-5/NFs for sustained and prolonged delivery of CUR not only remarkably reduced the expression levels of p16INK4A, a crucial modulator of cellular senescence but also led to a significant increase in the transcriptional level and activity of hTERT/telomerase and telomere extension, as well as osteoblastic differentiation markers. These findings demonstrated the potential of ZSM-5/NFs for sustained/controlled release of CUR therapeutic molecules in designing a novel platform toward counteracting cellular senescence and achieving sufficient quantities of fresh hADSCs for regenerative medicine applications.

Sustained release of curcumin self-emulsifying drug delivery system (SEDDS) from solvent-cast Soluplus® films

The objective of the present study was to investigate the feasibility of formulating and loading Curcumin SEDDS (Self-Emulsified Drug Delivery Systems) into films made from Soluplus® as the film-forming polymer. Films with up to 30% of Curcumin SEDDS were prepared by the solvent casting technique and analyzed for their mechanical and dissolution properties. A nine-run, two-factor, three-level factorial design was utilized to investigate the effect of SEDDS load (10, 20, and 30% w/w) and film thickness (10, 25, and 40 mils) on the tensile strength, elongation, and adhesiveness of the films. The dissolution profile of the films was also investigated by a USP Type 1 method. SEDDS loading was found to plasticize Soluplus® and to yield transparent films of good mechanical properties. Increasing SEDDS load, however, was found to reduce the tensile strength of the films, while increasing their adhesiveness and elongation. On the other hand, while an increase in film thickness was found to increase the tensile strength of the films, it reduced the elongation capacity of the films. Loading SEDDS into Soluplus® films was also found to sustain their release over 6 h, where a significant delay in release was found at lower SEDDS loads. This study demonstrated that Soluplus® can be used not only to formulate SEDDS into polymeric films but also to sustain their release over an extended time.

Loading natural emulsions with nutraceuticals by ultrasonication: Formation and digestion properties of curcumin-loaded soybean oil bodies

Curcumin is often used as a natural food additive because of its many drug functions and biological properties; however, its poor water solubility, chemical instability, ease of degradation, relatively high rate of metabolic degradation, and low bioavailability has limited its use in functional foods and medicines. In this study, we prepared curcumin oil body (COB) emulsions by loading curcumin into soybean slurry and explored the structural characteristics of emulsions prepared using different ultrasound sequences with the aim of enhancing the functionality and digestion properties of the oil bodies. The measured encapsulation efficiencies, particle sizes, ζ-potentials, Turbiscan stability indices, and other indicators reveal that the best COB encapsulation efficiency and stability are obtained using two ultrasound treatment methods and the addition of 10% oil. Structural analysis using infrared spectroscopy and sodium dodecyl sulfate–polyacrylamide gel electrophoresis revealed that the curcumin-loaded oil was mainly bound to the hydrophobic area of the protein on the surface of the oil body through hydrophobic interactions. COB stability was found to positively correlate with the amount of extrinsic protein adsorbed on the surfaces of the oil droplets. Digestion data showed that, compared with the method in which the oil body is prepared and then loaded with curcumin (COB–U), the COB prepared by direct ultrasonication in the soybean slurry (U–COB) realizes sustained oil release in the intestine. U–COB also exhibits higher bioavailability (67.42%), which is important for creating a more effective curcumin delivery system.

Effect of oxidized dextran on the stability of gallic acid-modified chitosan–sodium caseinate nanoparticles

We incorporated oxidized dextran (Odex) into nanoparticles composed of gallic acid-modified chitosan (GA-CS) and sodium caseinate (NaCas). The mass ratio of GA-CS to NaCas and the pH of the reaction solution were optimized to obtain nanoparticles with excellent performance and stability. The interactions among various nanomaterials were confirmed by Fourier-transform infrared spectroscopy (FT-IR) and fluorescence spectrometer. The optimized complex nanoparticles had a diameter of approximately 131.2 nm with a polydispersity index (PDI) of 0.14, and a zeta potential of 26.2 mV. Our results showed that Odex enhanced the stability and function of GA-CS/NaCas nanoparticles (NP). At a curcumin loading of 10%, the encapsulation efficiency of Odex-crosslinked GA-CS/NaCas (NP (Odex)) was 96.2%, whereas that for uncrosslinked nanoparticles was 66.9%. Compared to the burst release profile of free curcumin in simulated GI fluids, the sustained release profile of encapsulated curcumin was observed. Radical-scavenging assays confirmed that the nanoparticles had excellent antioxidant activity themselves due to the grafting of phenolic acid on chitosan backbone. Overall, NP (Odex) with good GI stability and antioxidant activity hold promising for the oral delivery of hydrophobic bioactives.

PH/ROS dual-sensitive and chondroitin sulfate wrapped poly (β-amino ester)-SA-PAPE copolymer nanoparticles for macrophage-targeted oral therapy for ulcerative colitis

An oral nanoparticle (NPs) encapsulated in chitosan/alginate hydrogel (CA-Gel) with dual-sensitive in pH and reactive oxygen species (ROS) was developed to load curcumin (CUR) based on the intracellular-specific characteristics of macrophages. Chondroitin sulfate (CS) wrapped PBAE-SA-PAPE with intracellular pH/ROS dual-sensitive characteristics and CUR via a simple nanoprecipitation method to form NPs (CS-CUR-NPs), and mixed CA-Gel to acquire the final preparation (CS-CUR-NPs-Gel). CS-CUR-NPs displayed an ideal average particle size (179.19±5.61nm) and high encapsulating efficiency (94.74±1.15%). CS showed a good targeting ability on macrophages and the CA-Gel contribution in protecting NPs from being destroyed in the upper gastrointestinal tract. As expected, CS-CUR-NPs-Gel could significantly alleviate inflammation in DSS-induced UC mice via TLR4-MAPK/NF-κB pathway. This study is the first to attempt to design a novel pH/ROS dual-stimulated release strategy in helping intracellular CUR delivery and anticipated for efficient anti-UC therapy.

Oral colon-targeting core\u2013shell microparticles loading curcumin for enhanced ulcerative colitis alleviating efficacy

BackgroundThe oral colon-targeting drug delivery vehicle is vital for the efficient application of curcumin (Cur) in ulcerative colitis (UC) treatment because of its lipophilicity and instability in the gastrointestinal tract.MethodsThe core–shell microparticle (MP) system composed of eco-friendly materials, zein and shellac, was fabricated using a coaxial electrospray technique. In this manner, Cur was loaded in the zein core, with shellac shell coating on it. The colon-targeting efficiency and accumulation capacity of shellac@Cur/zein MPs were evaluated using a fluorescence imaging test. The treatment effects of free Cur, Cur/zein MPs, and shellac@Cur/zein MPs in acute experimental colitis were compared.ResultsWith the process parameters optimized, shellac@Cur/zein MPs were facilely fabricated with a stable cone-jet mode, exhibiting standard spherical shape, uniform size distribution (2.84 ± 0.15 µm), and high encapsulation efficiency (95.97% ± 3.51%). Particularly, with the protection of shellac@zein MPs, Cur exhibited sustained drug release in the simulated gastrointestinal tract. Additionally, the in vivo fluorescence imaging test indicated that the cargo loaded in shellac@zein MPs improves the colon-targeting efficiency and accumulation capacity at the colonitis site. More importantly, compared with either free Cur or Cur/zein MPs, the continuous oral administration of shellac@Cur/zein MPs for a week could efficiently inhibit inflammation in acute experimental colitis.ConclusionThe shellac@Cur/zein MPs would act as an effective oral drug delivery system for UC management.

Curcumin-Loaded Iron Oxide Nanoparticles Coated with Sodium Alginate and Hydroxyapatite and Their Cytotoxic Effects Against the HT-29 and MCF-7 Cancer Cell Lines

Background: Curcumin, a bioactive component of Curcuma langa, has been investigated for its anti-proliferative effects against various cancer cell lines. Although results are very promising, the poor water solubility and low bioavailability of curcumin are its main limitations for clinical application. Objectives: The purpose of this study was to develop a drug delivery system, consisting of hydroxyapatite (HAp) polymer and sodium alginate (NaAlg), covering the magnetic core of iron oxide nanoparticles (IONPs), and loaded with curcumin in order to enhance its bioavailability and therapeutic efficacy. Methods: In this study, IONPs were prepared by the co-precipitation method and coated with HAp and NaAlg. The nanoparticles (NPs) were characterized by X-ray diffraction, Fourier transform infrared spectroscopy (FTIR), and electron microscopy (TEM and SEM). Encapsulation efficiency and curcumin loading rate were examined. Drug release rate was also measured in vitro at pH = 7.5 and 5.5. The toxicity of curcumin-loaded NPs and free curcumin was evaluated against HT-29 and MCF-7 cancer cells. Results: The assessment of physicochemical characteristics showed the synthesis of spherical particles with nanometer sizes (5 - 7 nm) and a high encapsulation efficiency (84.16 ± 3.51 %) and drug loading capacity (21.03 ± 0.87%). Maximum drug release was obtained at pH = 5.5. Iron oxide nanoparticles showed no significant cytotoxic effects. Curcumin-loaded coated IONPs showed a higher toxicity against HT-29 and MCF-7 cancer cells compared to free curcumin. Conclusions: This in vitro study showed that the encapsulation of curcumin, as a potent herbal drug, into IONPs enhanced its bioavailability, suggesting the NPs as an efficient vehicle for targeted drug delivery in cancer treatment.

A New Nanoparticulate System Based on Divanillin‐Crosslinked Starch: Mode of Manufacturing and In‐Vitro Evaluation of Skin Penetration

AbstractStarch nanoparticles (SNPs) attract special attention due to their natural origin as well as their biodegradable and biocompatible properties. Nanoparticles based on divanillin‐modified starch loaded with curcumin are manufactured through a simple procedure of nanoprecipitation by either the solvent dropping process or the non‐solvent dropping process, without any stabilizing agent. Curcumin loading is increased with divanillin concentration, and the entrapment efficiency for 15% divanillin‐crosslinked SNPs is determined as 58.7% ± 9.6% (15.6 ± 2.5 µg mg−1 lyophilized SNPs). Since the process uses gelatinized starch, retrogradation is evidenced by DSC thermograms of the SNPs. The DSC profiles of re‐gelatinization show three endothermic transitions which are dependent on the divanillin level. This study demonstrates that dermal application of curcumin‐containing SNPs crosslinked by 10% and 15% divanillin results in a significantly enhanced penetration of curcumin into porcine ear skin compared to the non‐crosslinked SNPs and 5% crosslinked SNPs. The study concludes therefore that the crosslinking method based on divanillin reaction with starch influences the encapsulation of curcumin in the SNPs and the ability of loaded SNPs to enhance curcumin penetration into the skin.

Balancing loading, cellular uptake, and toxicity of gelatin-pluronic nanocomposite for drug delivery: Influence of HLB of pluronic.

In this study, pluronic stabilized gelatin nanocomposite of varying hydrophilic-lipophilic balance (HLB) were synthesized to study the effect of surface hydrophobicity on their cellular uptake and in turn the delivery of a model hydrophobic bioactive compound, curcumin (CUR). Notably, the variation in HLB from 22 to 8 did not cause much change in morphology (~spherical) and surface charge (~ -6.5mV) while marginally reducing the size of nanocomposite from 165 ± 097 nm to 134 ± 074 nm. On contrary, nanocomposites exhibited a very significant increase in their numbers, hydrophobicity as well as CUR loading with decreasing HLB values (22-8) of pluronic. Further, the cellular uptake of CUR through pluronic-gelatin nanocomposites was studied in human lung carcinoma (A549) cells. The results indicated that cellular uptake of CUR through nanocomposites followed the order HLB 22 > HLB 18 > HLB 15 > HLB 8. This was also reflected in terms of the decrease in cytotoxicity of CUR through nanocomposite of HLB 8 as compared to that of HLB 22. Interestingly, bare nanocomposite of HLB 8 showed significantly higher cytotoxicity as compared to that of HLB 22. Together these results suggested that although higher hydrophobicity of the gelatin-pluronic nanocomposite facilitated higher entrapment of CUR, the carrier per se became toxic due to its hydrophobic interaction with lipid bilayer of plasma membrane. Thus, HLB parameter is very important in designing hybrid nanocomposite systems involving protein and pluronic to ensure both bio-compatibility of the carrier and the optimum cellular delivery of the pay load.

A Novel Bionic Catalyst-Mediated Drug Delivery System for Enhanced Sonodynamic Therapy.

Ultrasound (US)-triggered sonodynamic therapy (SDT) proves itself to be a formidable tool in the fight against cancer, due to its large spectrum of uses as a non-invasive therapeutic measure, while also demonstrating itself to be a certain improvement upon traditional SDT therapeutics. However, tumor hypoxia remains to be a major challenge for oxygen-dependent SDT. This study describes the development of an innovative, multi-use, catalyst-based and improved SDT targeting cancer, through the employment of a sonosensitizing curcumin (Cur) load embedded within a MnO2 core, together with an extraneous tumor cell membrane component. The latter allows for efficient tumor recognition properties. Hollowed-out MnO2 allows for efficient drug delivery, together with catalyzing oxygen generation from hydrogen peroxide present in tumor tissue, leading to enhanced SDT efficacy through the induction of a reduced hypoxic state within the tumor. In addition, Cur acts as a cytotoxic agent in its own right. The results deriving from in vivo studies revealed that such a biomimetic approach for drug-delivery actually led to a reduced hypoxic state within tumor tissue and a raised tumor-inhibitory effect within mouse models. Such a therapeutic measure attained a synergic SDT-based tumor sensitization treatment option, together with the potential use of such catalysis-based therapeutic formulations in other medical conditions having hypoxic states.

Nanocomplexes of curcumin and glycated bovine serum albumin: The formation mechanism and effect of glycation on their physicochemical properties

Bovine serum albumin (BSA) and BSA-glucose conjugates (GBSAⅠ and GBSAⅠI) with different extent of glycation were complexed with curcumin (CUR). The formation mechanism of BSA/GBSA-CUR complexes and the effect of glycation on their physicochemical properties were investigated. Fluorescence quenching and FTIR analysis indicated that the BSA/GBSA–CUR nanocomplexes were formed mainly by hydrophobic interactions. XRD analysis demonstrated that CUR was present in an amorphous state in the nanocomplexes. BSA with a greater extent of glycation (BSA < GBSAⅠ<GBSAⅠI) displayed a higher binding affinity for CUR. The highest CUR encapsulation efficiency (86.77%) and loading capacity (7.81 mg/g) were obtained in the GBSAⅠI-CUR nanocomplex. The zeta-potential varied from −17.45 to −27.65 mV, depending on the extent of glycation. Furthermore, the physicochemical stability of BSA/GBSA-CUR nanocomplexes increased with the increasing extent of glycation of BSA. Thus, the obtained GBSAⅠI have the potential to become new delivery carriers for encapsulating hydrophobic food components.

Preparation of ultra-long stable ovalbumin/sodium carboxymethylcellulose nanoparticle and loading properties of curcumin

OVA (ovalbumin)/CMC (sodium carboxymethylcellulose) nanoparticles are prepared by combining complex coacervation and thermal induction. The effect of different parameters on stability of OVA/CMC nanoparticles (different ratios, pH, temperature, salt concentration and storage time) is investigated. And then the loading and stabilizing mechanism of particles on curcumin are further analyzed. After heating, OVA and CMC in particle could further cross-linking and a highly salt-tolerant and ultra-long stable nanoparticle can be formed. OVA/CMC nanoparticle with the loose structure of wool ball could effectively load curcumin with the loading content and loading efficiency of 36.40 and 95.40%, 36.30 and 92.82%, 36.0 and 94.48% for the ratios of 1:2, 1:1 and 2:1, respectively. Curcumin-loaded of OVA/CMC nanoparticles show good DPPH· scavenging activity, Ferric-reducing ability and ABTS+ scavenging activity compared with curcumin/water. The results can be useful for designing food and beverage particle with improving bioactive substances functional properties.

In situ functionalizing calcium phosphate biomaterials with curcumin for the prevention of bacterial biofilm infections

This study developed a novel bioactive bone substitute (hydroxyapatite, HA) with improved anti-biofilm activity by functionalizing with curcumin (anti-biofilm compound) which provide sufficient flux of curcumin concentration for 14 days. The released curcumin acts to inhibit biofilm formation and control the number of viable planktonic cells simultaneously. To prepare curcumin-functionalized HA, different concentrations of curcumin (up to 3% w/v) were added simultaneously during the precipitation process of HA. The highest loading (50 mg/g HA) of curcumin onto HA was achieved with 2% w/v of curcumin. Physicochemical characterizations of curcumin-functionalized HA composites revealed that curcumin was successfully incorporated onto HA. Curcumin was sustainably released over 14 days, while higher curcumin release was observed in acidic condition (pH 4.4) compared to physiological (pH 7.4). The cytotoxicity assays revealed that no significant difference on bone cells growth on curcumin-functionalized HA and non-functionalized HA. Curcumin-functionalized HA was effective to inhibit bacterial cell attachment and subsequent biofilm maturation stages. The anti-biofilm effect was stronger against Staphylococcus aureus compared to Pseudomonas aeruginosa. The curcumin-functionalized HA composite significantly delayed the maturation of S. aureus compared to non-functionalized HA in which microcolonies of cells only begin to appear at 96 h. Up to 3.0 log reduction in colony forming unit (CFU)/mL of planktonic cells was noted at 24 h of incubation for both microorganisms. Thus, in this study we have suggested that curcumin loaded HA could be an alternative antimicrobial agent to control the risk of infections in post-surgical implants.

Development of Gelucire® 48/16 and TPGS Mixed Micelles and Its Pellet Formulation by Extrusion Spheronization Technique for Dissolution Rate Enhancement of Curcumin.

The oral bioavailability of curcumin is limited, attributed to its low solubility or dissolution and poor absorption. Herein, the study describes formulation of curcumin-loaded mixed micelles of Gelucire® 48/16 and TPGS for its dissolution rate enhancement. Curcumin was dispersed in these molten lipidic surfactants which was then adsorbed on carrier and formulated as pellets by extrusion spheronization. Critical micelle concentration (CMC) of binary mixture of Gelucire® 48/16 and TPGS was lower than their individual CMC demonstrating the synergistic behavior of mixture. Thermodynamic parameters like partition coefficient and Gibbs free energy of solubilization indicated that mixed micelles were more efficient than micelles of its individual components in curcumin solubilization. Dynamic light scattering (DLS) suggested slight increase in micellar size of mixed micelles than its components suggesting curcumin loading in mixed micelles. Fourier transform infrared spectroscopy (FTIR) revealed that phenolic hydroxyl group interacts with lipids which contribute to its enhanced solubility. Furthermore, the differential scanning calorimetry (DSC) and X-ray diffraction (XRD) study indicated the conversion of crystalline curcumin into amorphous form. In the pellet formulation, Gelucire® 48/16 acted as a binder and eliminated the requirement of additional binder. Microcrystalline cellulose (MCC) forms wet mass and retards the release of curcumin from pellets. Increase in concentration of water-soluble diluent increased drug release. The optimized formulation released more than 90% drug and maintains supersaturation level of curcumin for 2 h. Thus, mixed micellar system was effective delivery system for curcumin while pellet formulation is an interesting formulation strategy consisting semi-solid lipids.