Permeation Of Curcumin Research Articles

Curcumin and Quercetin-Loaded Lipid Nanocarriers: Development of Omega-3 Mucoadhesive Nanoemulsions for Intranasal Administration.

Curcumin (CUR) and quercetin (QU) are potential compounds for treatment of brain diseases such as neurodegenerative diseases (ND) because of their anti-inflammatory and antioxidant properties. However, low water solubility and poor bioavailability hinder their clinical use. In this context, nanotechnology arises as a strategy to overcome biopharmaceutical issues. In this work, we develop, characterize, compare, and optimize three different omega-3 (ω-3) fatty acids nanoemulsions (NEs) loaded with CUR and QU (negative, cationic, gelling) prepared by two different methods for administration by intranasal route (IN). The results showed that formulations prepared with the two proposed methods exhibited good stability and were able to incorporate a similar amount of CUR and QU. On the other side, differences in size, zeta potential, in vitro release kinetics, and permeation/retention test were observed. Considering the two preparation methods tested, high-pressure homogenization (HPH) shows advantages, and the CQ NE- obtained demonstrated potential for sustained release. Toxicity studies demonstrated that the formulations were not toxic for Caenorhabditis elegans. The developed ω-3 fatty acid NEs have shown a range of interesting properties for the treatment of brain diseases, since they have the potential to increase the nose-to-brain permeation of CUR and QU, enabling enhanced treatments efficiency.

Transdermal permeation of curcumin promoted by choline geranate ionic liquid: Potential for the treatment of skin diseases

The transdermal permeation of curcumin aided by choline and geranic acid ionic liquid (CAGE-IL) was addressed as a potential treatment for skin diseases. An in-depth analysis of the effect of CAGE-IL concentration in the enhancement of transdermal permeation of curcumin was performed, and the results were modelled via nonlinear regression analysis. The results obtained showed that a low percentage of CAGE-IL (viz. 2.0%, w/w) was effective in disrupting the skin structure in a transient fashion, facilitating the passage of curcumin dissolved in it.

Composition of Piperine with Enteric-Coated Chitosan Microspheres Enhances the Transepithelial Permeation of Curcumin in Sheep Intestinal Mucosa and Caco-2 Cells

Abstract Objectives The purpose of this study was to investigate the efficacy of enteric-coated chitosan microspheres with herbal bioenhancer, piperine, as a suitable composition for improving the permeation of curcumin through biological membranes using suitable ex vivo models. Material and Methods Chitosan microspheres of curcumin and piperine were prepared by an emulsion cross-linking method using glutaraldehydes the cross-linking agent and characterized for size, shape, entrapment efficiency, mucoadhesion, and in vitro release. The effect of piperine on the permeation of curcumin through excised sheep intestinal mucosa and Caco-2-cell monolayer was investigated. Statistical Analysis The data from permeation studies were analyzed by Student's t-test using Statistical Package for the Social Sciences (SPSS) software (SPSS, Chicago, IL, United States) with p-values <0.05 indicating statistical significance. Results The formulations showed mucoadhesion for a period of more than 6 hours which was influenced by the chitosan content. The rate of drug release of uncoated formulation followed first-order kinetics, and the mechanism of release was non-Fickian transport. Optimized formulation was coated with a pH-sensitive polymer, Eudragit S-100, by a solvent evaporation technique in different concentrations and evaluated for ex vivo permeation through sheep intestinal mucosa and Caco-2-cell monolayer. Scanning electron microscopy images of the optimized coated formulation showed spherical particles with smooth surfaces. The calculated permeation flux and permeability coefficient of curcumin from microspheres were at least 20% greater in the presence of piperine through the intestinal mucosa and 30% through the Caco-2-cell monolayer model. The permeability coefficient of curcumin from microspheres with piperine was 1.93 × 10 to 5 cm/sec and significantly greater (p < 0.05) than that of microspheres devoid of piperine and from aqueous dispersion (p < 0.005). Conclusion The study confirmed the contribution of piperine and mucoadhesive microspheres toward improved permeation of curcumin through biological membranes, thereby providing an approach that has the potential of increasing transport through intestinal epithelial cells and possibly enhancing the oral bioavailability of this drug.

Characterization and ex vivo evaluation of curcumin nanoethosomes for melanoma treatment

This study aimed at developing curcumin nanoethosomes (Cur-Ets) with superior skin permeation intended for melanoma treatment. Although curcumin is active against many types of skin cancers, a suitable topical formulation is still lacking due to its hydrophobicity and poor skin permeation. The formulation was characterized using Scanning Transmission Electron Microscopy (STEM), atomic force microscopy (AFM), ATR-FTIR, DSC and XRD. In vitro skin permeation was carried out using human skin, and the cytotoxicity of the formulation was evaluated on human melanoma cells (SK-MEL28). The vesicle size and zeta potential of the Cur-Ets were determined as 67 ± 1.6 nm and −87.3 ± 3.3 mV, respectively. STEM and AFM analysis further support the size and morphology of the formulation. Curcumin’s compatibility with formulation additives was confirmed by ATR-FTIR analysis. In addition, DSC and XRD analyses showed successful drug encapsulation in nanoethosomes. The drug encapsulation efficiency was determined as 87 ± 0.9%. The skin permeation of curcumin from Cur-Ets showed a superior flux (0.14 ± 0.03 µg cm−2 h−1) compared to the control (p < 0.05). Cytotoxicity of the formulation demonstrated a time-dependent and concentration-dependent antiproliferative activity against melanoma cells. The developed Cur-Ets is suggested as a promising topical formulation for melanoma treatment.

Formulation and Evaluation of Microemulsion of Curcumin in Thymol-Menthol Carrier System

Aim: To formulate and evaluate the Micro emulsion of curcumin in thymol-menthol carrier system.&#x0D; Study Design: Curcumin dissolves in mixture of thymol &amp; menthol to reasonable extent.100 mg of curcumin in 1 g of thymol and 0.6 g of menthol mixture was finalized as product mixture. The solution of curcumin in eutectic mixture being oily liquid, it gave the idea for development for the micro emulsion&#x0D; Place and Duration of Study: Department of Pharmaceutics and Department of Pharmacognosy, STES’s Smt. Kashibai Navale College of Pharmacy, Kondhwa (BK), National Chemical Laboratory, Pune between June 2016 and May 2017.&#x0D; Methodology: Micro emulsion system with eutectic mixture of thymol and menthol was chosen as oil phase and carrier for curcumin, tween 80 as surfactant and ethanol as co-surfactant. Ternary phase diagrams were constructed to obtain the optimum concentration range of oil phase, surfactant and co-surfactant. The micro emulsion of 100 mg curcumin containing 4.95 % oil phase, 33.39 % surfactant, 11.13% co-surfactant, 50:50% of water was optimum. Micro emulsion of curcumin was prepared by water titration method and evaluated for globule size, drug content, pH, viscosity, conductivity and In vitro drug release study. The ex-vivo permeation study for micro emulsion of curcumin was carried out on excised mice skin using Franz Diffusion apparatus. The cytotoxicity study for thymol, menthol was performed on healthy L929 murine fibroblast cell line. Anticancer activity of thymol-menthol eutectic mixture alone and with curcumin was performed on HeLa cell lines.&#x0D; Results: The preformulation studies did clearly indicate good compatibility of drug with thymol menthol carrier system. The cytotoxicity study was done on thymol – menthol(TM) as a preformulation aspect to ascertain the toxicity of these two excipients to be tried. It was found that TM was not cytotoxic in 120ug/mL concentration and thus was safe to be used in concentration below 120ug/mL. Batch B1 was optimised. The average globule size of micro emulsion was found to be 131.54 nm, zeta potential was found to be -0.57 mV. The drug content in micro emulsion batch B1 was determined and found to be 74.6%.Permeability study across mice skin ex-vivo model showed 52.38% permeability compared with curcumin alone which was 22.41%. So permeability of curcumin is enhanced substantially with micro emulsion made in thymol and menthol, owing to fact that thymol and menthol act as good permeation enhancers. The In vitro drug release study of micro emulsion was compared with curcumin alone. About 48.75% of curcumin was released from micro emulsion showed increase in release rate.&#x0D; Conclusion: Eutectic mixture of thymol and menthol showed promising results as penetration and solubility enhancer for curcumin. Solubility of curcumin was improved so as its rate of permeation which was used to develop formulation of micro emulsion with proven anticancer activity. The solubility of curcumin formulated with combination of eutectic mixture was increased up to 50 %.

Preparation, Characterization and Evaluation of the Anti-Inflammatory Activity of Epichlorohydrin-β-Cyclodextrin/Curcumin Binary Systems Embedded in a Pluronic®/Hyaluronate Hydrogel.

Curcumin (Cur) is an anti-inflammatory polyphenol that can be complexed with polymeric cyclodextrin (CD) to improve solubility and bioavailability. The aim of the present work was to prepare a CurCD hydrogel to treat inflammatory skin conditions. Epichlorohydrin-β-CD (EpiβCD) was used as polymeric CD. To characterize the binary system, solid-state and in-solution studies were performed. Afterwards, an experimental design was performed to optimize the hydrogel system. Finally, the CurEpiβCD hydrogel system was tested for anti-inflammatory activity using a HaCat psoriasis cell model. Co-grinded Cur/EpiβCD binary system showed a strong interaction and Curcumin solubility was much improved. Its combination with Pluronic® F-127/hyaluronate hydrogel demonstrated an improvement in release rate and Curcumin permeation. After testing its anti-inflammatory activity, the system showed a significant reduction in IL-6 levels. Hydrogel-containing CurEpiβCD complex is a great alternative to treat topical inflammatory diseases.

Preformulation Studies and Bioavailability Enhancement of Curcumin with a 'Two in One' PEG-β-Cyclodextrin Polymer.

Drug delivery systems are used to improve the biopharmaceutical properties of curcumin. Our aim was to investigate the effect of a water-soluble ‘two in one’ polymer containing covalently bonded PEG and βCD moieties (βCPCD) on the solubility and bioavailability of curcumin and compare it to a polymeric β-cyclodextrin (βCDP) cross-linked with epichlorohydrin. Phase-solubility and dynamic light scattering (DLS) experiments showed that the solubility of curcumin increased significantly in 10 m/m % βCPCD and βCDP solutions, but βCPCD–curcumin particles had higher hydrodynamic volume. The formation of the βCPCD–curcumin complex in solution and sedimented phase was confirmed by NMR spectroscopy. Biocompatibility and permeability experiments were performed on Caco-2 cells. Polymers did not show cytotoxicity up to 10 m/m % and βCPCD significantly increased the permeability of curcumin. DLS measurements revealed that among the interaction of polymers with mucin, βCPCD formed bigger aggregates compared to βCDP. Curcumin complexes were lyophilized into capsules and structurally characterized by micro-CT spectroscopy. Drug release was tested in a pH 1.2 medium. Lyophilized complexes had a solid porous matrix and both βCPCD and βCDP showed rapid drug release. βCPCD provides an opportunity to create a swellable, mucoadhesive matrix system for oral drug delivery.

Preparation of pectin-tannic acid coated core-shell nanoparticle for enhanced bioavailability and antihyperlipidemic activity of curcumin

As a functional polyphenolic compound, curcumin (CUR) has limited application due to its low solubility and bioavailability. In this work, curcumin loaded micelles self-assembled from disodium glycyrrhizin (Na2GA) was coated with pectin and tannic acid to construct a core-shell solid dispersion (SD-CUR). The assembly mechanism of the core-shell nanoparticle was clarified by molecular dynamics simulation. Improved solubility and in vitro release characteristics of SD-CUR in simulated gastric and intestinal juice were achieved. The parallel artificial membrane permeability (PAMPA) test confirmed that the permeability of curcumin in SD-CUR was significantly improved compared with the pure curcumin. Pharmacokinetic studies showed that the bioavailability was increased by 10 times. Intestinal in situ absorption study proved SD-CUR could enhance drug to transport across intestinal epithelial cells. Further hypolipidemic study demonstrated that the SD-CUR medication group could considerably reduce the levels of total cholesterol (TC), triglyceride (TG), and low density lipoprotein (LDL) in hyperlipidemia rats. These findings confirmed that SD-CUR had broad application prospects in the prevention and treatment of hyperlipidemia.

Transferrin-functionalized lipid nanoparticles for curcumin brain delivery

Curcumin is an anti-inflammatory and antioxidant compound with potent neuroprotective activity. Due to its poor water solubility, low bioavailability, rapid elimination and the challenges for crossing and transposing the blood-brain barrier (BBB), solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) loaded with curcumin were successfully produced and functionalized with transferrin, in order to mediate the transport of these particles through the BBB endothelium to the brain.The nanosystems revealed Z-averages under 200 nm, polydispersity index below 0.2 and zeta potential around -30 mV. Curcumin encapsulation around 65 % for SLNs and 80 % for NLCs was accomplished, while the functionalized nanoparticles presented a value around 70–75 %. A stability study revealed these characteristics remained unchanged for at least 3 months. hCMEC/D3 cells viability was firstly analysed by MTT and LDH assays, respectively, and a concentration of 10 μM of curcumin-loaded nanoparticles were then selected for the subsequent permeability assay. The permeability study was conducted using transwell devices with hCMEC/D3 cells monolayers and a 1.5-fold higher permeation of curcumin through the BBB was verified. Both SLNs and NLCs are promising for curcumin brain delivery, protecting the incorporated curcumin and targeting to the brain by the addition of transferrin to the nanoparticles surface.

Formulation Design and Evaluation of Solid Lipid Micro-particles of Curcumin for the Treatment of Alzheimer’s disease

Solid lipid microparticles reach the site of its action in a controlled rate and do show controlled release for a better therapeutic result. A good drug carrying and release system involve a controlled drug delivery that improves bioavailability, to enrich stability and to minimise the toxic effects followed with a targeted drug at the site of its action. The solid lipid microparticles of curcumin were prepared in a view to achieving high permeability of curcumin in the brain through blood-brain-barrier. The lipid microsphere solids were prepared by hot melts microencapsulation technique to formulate solid lipid microspheres. Twelve lipid formulations were prepared with varying concentration of surfactants (span 40, span 70, span 90 and Tween 100). The developed formulation was subjected to various parameters such as the particle size, % entrapment efficiencies, yield productions, % cumulative release, percentage yield and drug loading, based upon highest entrapment efficiency, drug release and % cumulative release, the F3 formulation was considered as the best formulation. The prepared microsphere was subjected to different evaluation parameters such as thin-layer chromatography, melting point, FTIR, solubility, compatibility study and In-vitro drug release. The developed formulation shows spherical and smooth surface. The percentage release of drug F3 formulation has been found highest of about 86.23% after 12 hr.

Incorporation of curcumin in liquid nanodomains embedded into polymeric films for dermal application

Liquid nanovehicles are gaining interest in drug delivery because of the high solubilization capacity of bioactives at their interface and enhanced permeation of compounds across physiological membranes. However, the dermal application of liquid nanovehicles is still limited. The goal of this research is to develop a dermal delivery system based on embedding of liquid nanovehicles into polymeric films, which will allow controlled release of the nanodroplets with the solubilized drug.In this study, we describe the incorporation of empty and curcumin-loaded nanodomains into polymeric film. The novel technology results in formation of homogeneous, transparent and elastic films with high (up to 85 wt%) loading capacity of nanodomains. The fundamental structural characterizations show that nanodomain structures embedded in the dry film are spontaneously reformed during the dermal application with similar droplets size of 10 nm. Ex-vivo release studies were performed on Franz diffusion cells and demonstrated a significant permeation of curcumin through the pig skin.This novel film technology can serve as a "solid platform reservoir" for liquid nanovehicles which enables controlled release of nanodroplets with solubilized bioactive.

Nanoemulsion loaded polymeric hydrogel for topical delivery of curcumin in psoriasis

Curcumin is a natural compound with multiple molecular targets that causes inhibition of factors involved in pathogenesis of psoriasis but low solubility and poor skin penetrability limit its efficacy. The current study aimed to increase the solubility and skin penetrability of curcumin after topical application. The curcumin nanoemulsion was optimized by low-energy emulsification method and converted into nano-emulgel using crosslinked polyacrylic acid (carbopol 934) as a gelling agent. To achieve high loading, transcutol-HP (105.40 ± 3.84 mg/g) and acconon-MC8-2 (104.73 ± 2.85 mg/g) were explored as potential solubilizer for curcumin. Despite the high solubility of curcumin in acconon-MC8-2, it showed physical incompatibility while transcutol-HP found to be compatible with labrafac PG being an oil system for the development of nanoemulsion in presence of tween 20 (surfactant) and solutol-HS15 (co-surfactant). The droplet size of developed formulation was 10.57 nm with low PdI (0.094) and negative zeta potential (−18.7 mV). The release of curcumin from nanoemulsion follows Korsmeyer-Peppas kinetic with fickian diffusion and exhibited 4.87-fold increase in permeation of curcumin from developed nano-emulgel. The nano-emulgel formulation exhibited quicker and early healing in psoriatic mice compared to curcumin, and betamethasone-17-valerate gel. The results showed that curcumin nanoemugel is a promising candidate for the better long-term management of psoriasis.

Neuroprotection by curcumin: A review on brain delivery strategies.

Neurodegenerative diseases are a major global public health concern in the elderly population but therapeutic options are limited. Curcumin is a hydrophobic polyphenol extracted from the dried rhizomes of Curcuma longa L. and shows good potential for the treatment of neurodegenerative diseases and brain tumors. The blood-brain barrier (BBB) is the major obstacle for the delivery of curcumin into the brain, limiting its therapeutic potential. The development of promising approaches to facilitate curcumin transportation across the BBB may resolve some of the problems associated with drug delivery. Studies have shown nano delivery of curcumin can improve a number of outcome measures in neurodegenerative diseases. The present review highlights current and emerging strategies to facilitate curcumin permeation across the BBB for the treatment of various neurodegenerative diseases.

Mucoadhesive emulgel systems containing curcumin for oral squamous cell carcinoma treatment: From pre-formulation to cytotoxicity in tissue-engineering oral mucosa

Current oral squamous cell carcinoma chemotherapies demonstrate off-target toxicity, which could be reduced by local delivery. Curcumin acts via many cellular targets to give anti-cancer properties; however the bioavailability is hindered by its physicochemical characteristics. The incorporation of curcumin into emulgel systems could be a promising approach for its solubilization and delivery. The aim of this work was to develop emulgel systems containing curcumin for the treatment of oral cancer. The emulgels containing curcumin were prepared with poloxamer 407, acrylic acid derivatives, oil phase (sesame oil or isopropyl myristate). The more stable system was evaluated for mechanical and rheological properties, as well as, the in vitro drug release profile, permeation and cytotoxic potential to oral mucosa models. The flow-throw system evidenced that the formulations could keep 5 min over porcine oral mucosa. Emulgel showed pseudoplastic behavior and a gelation temperature of 33 °C, which ensure their higher consistency. In addition, 70% of the incorporated curcumin was released within 24 h in an in vitro drug release study and could permeate porcine oral mucosa. Monolayers cultures and tissue-engineered models showed the selectivity of the drug and systems for tumor cells. The physicochemical properties, subsequent release and permeation of curcumin to selectivity kill cancer cells could be improved by the incorporation into emulgel systems.

Film-Forming Nanogels: Effects of Nanocarriers and Film-Forming Gel on the Sustained Release of Curcumin.

Although film-forming hydrogels possess the advantages of both film and hydrogel dosage forms, certain limitations still remain. This study aims to investigate the use of film-forming hydrogels and the effects of nanocarriers on the sustained release of a poorly water-soluble drug, curcumin. The film-forming hydrogels contained either zein or polyvinylpyrrolidone as a film former, in addition to hydroxypropyl methylcellulose, oleic acid, ethanol and water. Curcumin was encapsulated in poly(lacticco- glycolic acid) and gelatine nanoparticles using a sonoprecipitation method. Free drug and drug-loaded nanoparticles were later dispersed into blank hydrogels to produce the film-forming nanogels. The results suggested that the encapsulation of curcumin in nanoparticles could reduce the drug particle size to less than 200nm for easier diffusion and could shield curcumin from chemical interactions that limit its topical permeability. Curcumin was more compatible with gelatine nanoparticles than with poly(lactic-coglycolic acid) nanoparticles, and gelatine nanoparticles, in turn, were more compatible with zein than with polyvinylpyrrolidone film-forming nanogels. Therefore, gelatine nanoparticles in zein film-forming nanogels greatly elevated the permeability of curcumin by over five times that afforded by gelatine nanoparticles in polyvinylpyrrolidone film-forming nanogels. This research suggested that film-forming nanogel is a promising drug delivery system for both improved permeability and sustained topical diffusion of the extremely hydrophobic drug curcumin depending on the compatibility between the nanocarrier and the film-forming hydrogel.

Mechanistic Evaluation of Enhanced Curcumin Delivery through Human Skin In Vitro from Optimised Nanoemulsion Formulations Fabricated with Different Penetration Enhancers.

Curcumin is a natural product with chemopreventive and other properties that are potentially useful in treating skin diseases, including psoriasis and melanoma. However, because of the excellent barrier function of the stratum corneum and the relatively high lipophilicity of curcumin (log P 3.6), skin delivery of curcumin is challenging. We used the principles of a Quality by Design (QbD) approach to develop nanoemulsion formulations containing biocompatible components, including Labrasol and Lecithin as surfactants and Transcutol and ethanol as cosurfactants, to enhance the skin delivery of curcumin. The nanoemulsions were characterised by cryo-SEM, Zeta potential, droplet size, pH, electrical conductivity (EC) and viscosity (η). Physicochemical long-term stability (6 months) was also investigated. The mean droplet sizes as determined by dynamic light scattering (DLS) were in the lower submicron range (20–50 nm) and the average Zeta potential values were low (range: −0.12 to −2.98 mV). Newtonian flow was suggested for the nanoemulsions investigated, with dynamic viscosity of the nanoemulsion formulations ranging from 5.8 to 31 cP. The droplet size of curcumin loaded formulations remained largely constant over a 6-month storage period. The inclusion of terpenes to further enhance skin permeation was also examined. All nanoemulsions significantly enhanced the permeation of curcumin through heat-separated human epidermal membranes, with the greatest effect being a 28-fold increase in maximum flux (Jmax) achieved with a limonene-based nanoemulsion, compared to a 60% ethanol in water control vehicle. The increases in curcumin flux were associated with increased skin diffusivity. In summary, we demonstrated the effectiveness of nanoemulsions for the skin delivery of the lipophilic active compound curcumin, and elucidated the mechanism of permeation enhancement. These formulations show promise as delivery vehicles for curcumin to target psoriasis and skin cancer, and more broadly for other skin delivery applications.

Phytoglycogen, a natural dendrimer-like glucan, improves the soluble amount and Caco-2 monolayer permeation of curcumin and enhances its efficacy to reduce HeLa cell viability

This study evaluated the potential of phytoglycogen (PG) to solubilize curcumin (CCM) and improve its in vitro permeation and anticancer efficacy. CCM and PG were incorporated using co-solvent mixing followed by spray- or vacuum-drying. The obtained CCM/PG solid dispersions were evaluated for soluble CCM amount, CCM-PG interactions, Caco-2 monolayer permeation, and inhibitory efficacy against HeLa cells. Results showed that preparation method and PG-to-CCM ratio affected CCM soluble amount, favoring spray-drying and high PG-to-CCM ratios. FTIR spectra suggested the presence of hydrogen bonding between CCM and PG in spray-dried solid dispersions. For Caco-2 monolayer permeation, CCM/PG solid dispersion resulted in the basolateral CCM accumulation of 0.53 μg per well in 120 min, compared with 0.13 μg for curcumin alone. In particular, CCM/PG solid dispersions showed much greater efficacy than CCM alone in reducing the viability of HeLa cells, suggesting the potential of PG to enable CCM as a bioactive compound.

Electrospun curcumin/polycaprolactone/copolymer F‐108 fibers as a new therapy for wound healing

ABSTRACTThe application of fibers associated with drugs is a promising alternative to meet the clinical needs of tissue repair. Curcumin exhibits great cicatricial potential because it has numerous pharmacological properties. This research aimed to produce fibers of polycaprolactone and copolymer F‐108 associated with curcumin and to evaluate in vivo their action on the process of wound healing. The fibers were produced by electrospinning technique and characterized by scanning electron microscopy (SEM), X‐ray diffractometry (XRD), and fluorescence microscopy. They were applied in cutaneous wounds of rats for the analysis of photoacoustic permeation and histological study. The characterization showed that the electrospinning allowed the preparation of homogeneous material with curcumin. The fibers benefited healing of the wounds and allowed the permeation of curcumin at all stages. The use of PCL/F‐108 fibers allowed the elaboration of a new curcumin delivery system, improving its bioavailability and action in the healing of excisional wound. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48415.

Enhancing the oral bioavailability of curcumin using solid lipid nanoparticles

To control the oral bioavailability of curcumin, we fabricated solid lipid nanoparticles (SLNs) using tristearin and polyethylene glycol (PEG)ylated emulsifiers. Lipolysis of prepared SLNs via simulated gastrointestinal digestion was modulated by altering the types and concentrations of emulsifiers. After digestion, the size/surface charge of micelles formed from SLN digesta were predictable and >91% of curcumin was bioaccessible in all of the SLNs. The curcumin permeation rate through mucus-covered gut epithelium in vitro was dependent on the size/surface charge of the micelles. Curcumin loaded in long-PEGylated SLNs rapidly permeated the epithelium due to the neutral surface charge of the micelles, resulting in a >12.0–fold increase in bioavailability compared to curcumin solution in a rat model. These results suggest that the bioavailability of curcumin can be controlled by modulating the interfacial properties of SLNs, which will facilitate the development of curcumin formulations for use in functional foods and pharmaceuticals.

Cyclodextrin nanosponge based hydrogel for the transdermal co-delivery of curcumin and resveratrol: Development, optimization, in vitro and ex vivo evaluation

The present study aims at the design of the transdermal co-delivery of curcumin (CUR) and resveratrol (RES) using cyclodextrin nanosponge based hydrogel. Cyclodextrin-based nanosponges (CDNS) were prepared by crosslinking cyclodextrin using pyromellitic dianhydride, loaded with curcumin and resveratrol, characterized and studied for synergism against breast cancer cells by in vitro cytotoxicity test. The nanosponges enhanced the in-vitro release of curcumin to 10 folds and resveratrol release to 2.5 folds compared to plain curcumin and resveratrol. CUR-CDNS and RES-CDNS combination showed a synergistic cytotoxic effect on MCF-7 cells with a combination index value of 0.29. A hydrogel base using carbomer and propylene glycol was developed to incorporate CUR-CDNS and RES-CDNS. The formulation was optimized for CUR, RES flux and gel property using 3-factor 3-level Box-Behnken design. The optimized hydrogel formulation was evaluated for physicochemical, photostability study, in vitro and ex vivo permeation study. Photostability of curcumin and resveratrol in CDNS-hydrogel formulation was increased to almost 5 and 7 folds respectively compared to hydrogel formulated without CDNS. The permeation of curcumin and resveratrol were significantly enhanced when delivered using CDNS-hydrogel base. The present work proposes the use of cyclodextrin nanosponge based hydrogel as an effective transdermal delivery system for curcumin and resveratrol co-delivery.