Project description:The nutraceutical system of curcumin-piperine in 2-hydroxypropyl-β-cyclodextrin was prepared by using the kneading technique. Interactions between the components of the system were defined by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR). Application of hydroxypropyl-β-cyclodextrin as a carrier-solubiliser improved solubility of the curcumin-piperine system, its permeability through biological membranes (gastrointestinal tract, blood-brain barrier) as well as the antioxidant, antimicrobial and enzyme inhibitory activities against acetylcholinesterase and butyrylcholinesterase.
Project description:The oral delivery system is very important and plays a significant role in increasing the solubility of drugs, which eventually will increase their absorption by the digestive system and enhance the drug bioactivity. This study was conducted to synthesize a novel curcumin nano lipid carrier (NLC) and use it as a drug carrier with the help of computational molecular docking to investigate its solubility in different solid and liquid lipids to choose the optimum lipids candidate for the NLCs formulation and avoid the ordinary methods that consume more time, materials, cost, and efforts during laboratory experiments. The antiviral activity of the formed curcumin-NLC against SARS-CoV-2 (COVID-19) was assessed through a molecular docking study of curcumin's affinity towards the host cell receptors. The novel curcumin drug carrier was synthesized as NLC using a hot and high-pressure homogenization method. Twenty different compositions of the drug carrier (curcumin nano lipid) were synthesized and characterized using different physicochemical techniques such as UV-Vis, FTIR, DSC, XRD, particle size, the zeta potential, and AFM. The in vitro and ex vivo studies were also conducted to test the solubility and the permeability of the 20 curcumin-NLC formulations. The NLC as a drug carrier shows an enormous enhancement in the solubility and permeability of the drug.
Project description:Pro-liposome is a type of drug delivery system (DDS) with numerous advantages as a stable material with various applicability for several pharmaceutical dosage forms, to effectively deliver the material to reach its target in the human body. Nevertheless, it is mostly designed by employing an organic solvent hence giving rise to safety issues. We have developed a method for the preparation of organic solvent-free liposomes composed of soy lecithin and cholesterol by highlighting the importance of temperature during the initial mixing process, a self-hydration of a thin layer spread film, and a spray-drying technique with a suitable excipient as the carrier. The method was successfully applied to prepare a stable pro-liposome containing 0.17% (w/w) of piperine with an encapsulation efficiency of 95.58 ± 2.91%. Moreover, the study revealed that a piperine molecule forms hydrophobic interaction with six of the adjacent phospholipids in the liposome structure, this information can be useful for researchers designing similar studies. In conclusion, organic solvent-free pro-liposome can be an alternative method in the development of DDS, and several factors could be continuously improved to fulfill the intended pro-liposome characteristic.
Project description:Anticancer drug-loaded nanoparticles have been explored extensively to decrease side effects while improving their therapeutic efficacy. However, due to the low drug loading content, premature drug release, nonstandardized carrier structure, and difficulty in predicting the fate of the carrier, only a few nanomedicines have been approved for clincial use. Herein, a carrier-free nanoparticle based on the self-assembly of the curcumin-erlotinib conjugate (EPC) is developed. The EPC nanoassembly exhibits more potent cell killing, better antimigration, and anti-invasion effects for BxPC-3 pancreatic cancer cells than the combination of free curcumin and erlotinib. Furthermore, benefiting from both passive and active tumor targeting effect, EPC nanoassembly can effectively accumulate in the tumor tissue in a xenograft pancreatic tumor mouse model. Consequently, EPC effectively reduces the growth of pancreatic tumors and extends the median survival time of the tumor-bearing mice from 22 to 68 days. In addition, no systemic toxicity is detected in the mice receiving EPC treatment. Attributed to the uniformity of the curcumin-erlotinib conjugate and easiness of scaling up, it is expected that the EPC can be translated into a powerful tool in fighting against pancreatic cancer and other epidermal growth factor receptor positive cancers.
Project description:The systemic administration of paclitaxel (PTX)-based combinatorial therapies is significantly restricted due to the multidrug resistance. Curcumin (CUR) not only inhibits cancer-cell proliferation but also reverses the PTX resistance. However, achieving codelivery of these two drugs is a challenge due to their poor water solubility. Herein, we synthesized carrier-free PTX NPs by a facile nanoprecipitation method with the help of CUR and other curcuminoids present in turmeric extract. The prepared NPs demonstrated spherical morphologies with high conformational stability. Experimental studies showed that the presence of both bisdemethoxycurcumin and demethoxycurcumin is essential for the successful formation of spherical and monodisperse NPs. Computational studies revealed that the presence of the more sterically available curcuminoids BMC and DMC makes the self-assembly procedure more adaptable with a higher number of potential conformations that could give rise to more monodisperse PTX-CUR NPs. Compared with PTX alone, PTX-CUR NPs have shown comparable therapeutic efficiency in vitro and demonstrated a higher cellular internalization, highlighting their potential for in vivo applications. The successful formation of PTX-CUR NPs and the understanding of how multiple drugs behave at the molecular level also provide guidance for developing formulations for the synthesis of high-quality and effective carrier-free nanosystems for biomedical applications.
Project description:Curcumin (Cur.) is a natural product isolated from the rhizome of Curcuma longa, with a variety of biological and pharmacological activities in food and pharmaceutical products. However, curcumin's poor solubility in water greatly limits its bioavailability and clinical applications. In this study, co-grinding curcumin with food additives produced a mixture, which was evaluated for the solubility in water, dissolution, material morphology, in vivo bioavailability, cell uptake and entry mechanism. We tested 9 food additives in total and found that poloxamers performed the best. The 2 co-grinding mixtures Cur./Kolliphor® P407 and Cur./Kolliphor® P188 with high drug loading at 65.5% significantly improved the curcumin aqueous solubility, subsequently increased its intestinal epithelial cell uptake and oral bioavailability. The relative bioavailabilities for the 2 co-grinding mixtures were 309% and 163%, respectively, compared with curcumin API. Co-grinding process has a broad application prospect and is suitable for industrial production.
Project description:Nanodisks (NDs) are nanoscale, disk-shaped phospholipid bilayers whose edge is stabilized by apolipoproteins. In the present study, NDs were formulated with the bioactive polyphenol curcumin at a 6:1 phospholipid-to-curcumin molar ratio. Atomic force microscopy revealed that curcumin-NDs are particles with diameters <50 nm and the thickness of a phospholipid bilayer. When formulated in NDs, curcumin is water soluble and gives rise to a characteristic absorbance spectrum with a peak centered at 420 nm. Fluorescence spectroscopy of curcumin-NDs provided evidence of self-quenching. Incubation of curcumin-NDs with empty NDs relieved the self-quenching, indicating redistribution of curcumin between curcumin-loaded and empty NDs. In HepG2 cells, curcumin-NDs mediated enhanced cell growth inhibition as compared with free curcumin. In a cell culture model of mantle cell lymphoma, curcumin-NDs were a more potent inducer of apoptosis than free curcumin. The nanoscale size of the complexes, combined with their ability to solubilize curcumin, indicates NDs may have in vivo therapeutic applications.Nanodisks (NDs), disk-shaped phospholipid bilayers stabilized by apolipoproteins, are shown entrap curcumin and improve its delivery to HepG2 and mantle cell lymphoma cells in culture. These novel nanocomplexes demonstrate interesting therapeutic application potentials.
Project description:Conjugation of small molecule agonists of Toll-like receptor 7 (TLR7) to proteins, lipids, or polymers is known to modulate potency, and the physical form or formulation of these conjugates is likely to have a major effect on their immunostimulatory activity. Here, we studied the effect of formulation on potency of a 1,2‑di‑(9Z‑octadecenoyl)‑sn‑glycero‑3‑phosphoethanolamine (DOPE) conjugated TLR7 agonist (DOPE-TLR7a) alongside assessing physical form using Dynamic Light Scattering (DLS), Nanosight Particle Tracking (NTA) analysis and Small Angle X-ray Scattering (SAXS). A very high potency of DOPE-TLR7a conjugate (EC50 around 9 nM) was observed either when prepared by direct dilution from DMSO or when formulated into 400-700 nm large multilamella liposomes containing dimethyldioctadecylammonium bromide salt (DDA) and DOPE. When prepared by dissolution in DMSO followed by dilution in aqueous culture medium, 93 ± 5 nm nanoparticles were formed. Without dilution from solution in DMSO, no nanoparticles were observed and no immunostimulatory activity could be detected without this formulation step. SAXS analysis of the conjugate after DMSO dissolution/water dilution revealed a lamellar order with a layer spacing of 68.7 Å, which correlates with arrangement in groups of 3 bilayers. The addition of another immunostimulatory glycolipid, trehalose‑6,6‑dibehenate (TDB), to DOPE:DDA liposomes gave no further increase in immunostimulatory activity beyond that provided by incorporating DOPE-TLR7a. Given the importance of nanoparticle or liposomal formulation for activity, we conclude that the major mechanism for increased potency when TLR7 agonists are conjugated to macromolecules is through alteration of physical form.
Project description:Tamoxifen is a prodrug that is primarily metabolized into the pharmacologically active metabolite endoxifen and eventually into inactive metabolites. The herb curcumin may increase endoxifen exposure by affecting phase II metabolism. We compared endoxifen and tamoxifen exposure in breast cancer patients with or without curcumin, and with addition of the bio-enhancer piperine. Tamoxifen (20⁻30mg per day (q.d.)) was either given alone, or combined with curcumin (1200 mg three times daily (t.i.d.)) +/- piperine (10 mg t.i.d.). The primary endpoint of this study was the difference in geometric means for the area under the curve (AUC) of endoxifen. Genotyping was performed to determine CYP2D6 and CYP3A4 phenotypes. The endoxifen AUC0⁻24h decreased with 7.7% (95%CI: -15.4 to 0.7%; p = 0.07) with curcumin and 12.4% (95%CI: -21.9 to -1.9%; p = 0.02) with curcumin and piperine, compared to tamoxifen alone. Tamoxifen AUC0⁻24h showed similar results. For patients with an extensive CYP2D6 metabolism phenotype (EM), effects were more pronounced than for intermediate CYP2D6 metabolizers (IMs). In conclusion, the exposure to tamoxifen and endoxifen was significantly decreased by concomitant use of curcumin (+/- piperine). Therefore, co-treatment with curcumin could lower endoxifen concentrations below the threshold for efficacy (potentially 20⁻40% of the patients), especially in EM patients.
Project description:The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols, curcumin, and piperine are able to modulate the self-renewal of normal and malignant breast stem cells, we examined the effects of these compounds on mammosphere formation, expression of the breast stem cell marker aldehyde dehydrogenase (ALDH), and Wnt signaling. Mammosphere formation assays were performed after curcumin, piperine, and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells, selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation, serial passaging, and percent of ALDH+ cells by 50% at 5 microM and completely at 10 microM concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 microM and completely at 10 microM. Curcumin and piperine separately, and in combination, inhibit breast stem cell self-renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment can be a mechanistic biomarker for use in human clinical trials.