Cyclodextrin Complexes Research Articles

Development and validation of HPLC method for simultaneous quantification of alpha-tocopherol (free or encapsulated) and cholesterol in semen cryopreservation media.

The HPLC method was developed and validated for assaying alpha-tocopherol and cholesterol in cryopreservation media. Chromatographic separation was performed on an isocratic system, using a C-18 column. The mobile phase was composed of a mixture of methanol:acetonitrile:water 68:28:4 (v/v/v), using a flow rate of 1.5 mL/min and 20 μL injection volume, at a wavelength of 208 nm. The method was validated according to International Conference on Harmonization guidelines. The method proved to be specific, accurate, precise, and linear with correlation coefficients greater than 0.996 over a wide concentration range of both analytes. Vitamin E and cholesterol presented limits of detection of 0.002 mg/mL, 0.026 mg/mL and limits of quantitation of 0.006 mg/mL, 0.086 mg/mL, respectively. This method is simple and rapid, shows high precision and accuracy, and offers the advantage of simultaneous assaying of vitamin E and cholesterol (alone, in cyclodextrins complexes or in liposome loaded) on semen cryopreservation media.

Gelatin scaffolds loaded with asiaticoside/2‐hydroxypropyl‐β‐cyclodextrin complex for use as wound dressings

Gelatin (Gel) is a protein polymer obtained from the hydrolysis of collagen. Gel was used to prepare a wound dressing material loaded with asiaticoside (AC), a trisaccharide triterpene from Centella asiatica (L.) Urban commonly used in wound healing and dermis reconstruction. To improve water solubility, AC was formed into an inclusion complexation with 2‐hydroxypropyl‐β‐cyclodextrin (HPβCD) in molar ratios of 1:0.5, 1:1, and 1:2. The AC/HPβCD complexes were then loaded into a standard Gel solution and glutaraldehyde was used as the crosslinking of the Gel matrix. Freeze‐drying was used to fabricate the mixed solutions into Gel scaffolds. Average pore sizes of the scaffolds ranged between 548 and 560 μm. The compressive modulus of the scaffolds increased with increasing HPβCD molar ratio. Swelling and weight loss of the scaffolds in water increased with longer submersion times. Highest cumulative released amount of AC was obtained from the scaffold incorporated with the AC/HPβCD complex at the molar ratio of 1:2. Indirect cytotoxicity assay with human dermal fibroblasts confirmed that AC/HPβCD complex‐loaded Gel scaffolds were non‐toxic to the cells. Results demonstrated the potential of AC/HPβCD complex‐loaded Gel scaffolds for use as wound dressing materials.

Formulation of Piperine Ternary Inclusion Complex Using β CD and HPMC: Physicochemical Characterization, Molecular Docking, and Antimicrobial Testing

The present study was designed to evaluate the effect of hydroxyl propyl methyl cellulose (HPMC) on the complexation efficiency and dissolution of piperine (PPR) and β cyclodextrin (β CD) complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and microwave irradiation methods. The samples were further evaluated for physicochemical evaluation, morphology, antimicrobial, and antioxidant activities. The binary and ternary samples showed high stability constant (Ks) value and complexation efficiency (CE). The dissolution study results revealed marked enhancement in the release of the binary inclusion complex and ternary inclusion complex compared to pure PPR. Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), and molecular docking results confirm the complex formation. X-ray powder diffractometry (XRD) and scanning electron microscopy (SEM) data revealed modification in the structure of PPR. 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and antimicrobial results showed enhanced activity in the PPR complex in comparison to pure PPR. In conclusion, a remarkable enhancement in dissolution, antioxidant and antimicrobial activities were attained due to marked improvement in solubility through complexation of PPR with HPMC/β CD.

Complexation with Random Methyl-β-Cyclodextrin and (2-Hydroxypropyl)-β-Cyclodextrin Promotes Chrysin Effect and Potential for Liver Fibrosis Therapy.

Liver fibrosis results from chronic liver injury and is characterized by the accumulation of extracellular matrix in excess driven by hepatic stellate cells (HSCs) activation. Chrysin (CHR) is a natural flavonoid that is limited by its low solubility to exert its anti-inflammatory, antioxidant and anti-fibrotic properties. The aim of this study was to investigate the biocompatibility of CHR complexes with two cyclodextrins (CDs)-(2-hydroxypropyl)-β-cyclodextrin (HPBCD) and random methyl-β-cyclodextrin (RAMEB), and their potential to induce anti-inflammatory, antioxidant and anti-fibrotic effects. Biocompatibility of the complexes was evaluated on Huh7 and LX2 cell lines: MTT and Live/Dead tests indicated the cell viability and an LDH test showed the cytotoxicity. Immunohistochemical staining of Nuclear Factor Kappa B (NF-κB) nuclear translocation was performed to evaluate the anti-inflammatory effect of the complexes. Oxygen Radical Absorbance assay, Superoxide Dismutase activity and Glutathione Peroxidase (GPx) assays indicated the antioxidant properties of the chrysin complexes. Finally, the complexes’ anti-fibrotic potential was evaluated at the protein and gene level of α-sma. In HSCs, CDs induced higher cytotoxicity correlated with lower cell viability than CHR–CD. The 1:1 CHR–RAMEB pretreatment avoided p65 translocation. The 1:2 CHR–RAMEB complex increased ORAC values, improved SOD activity and produced the highest stimulation of GPx activity. CHR–RAMEB reduced α-sma expression at lower concentration than CHR–HPBCD, proving to be more efficient. In conclusion, both CHR–CD complexes proved to be biocompatible, but CHR–RAMEB showed improved anti-inflammatory, antioxidant and anti-fibrotic effects that could recommend its further use in liver fibrosis treatment.

Трансформация гидрофобных флавоноидов катехина, дигидрокверцетина и кверцетина в водорастворимые структуры

The paper describes methods for the transformation of poorly water-soluble flavonoids: dihydroquercetin, catechin and quercetin into water-soluble forms during the formation of supromolecular adducts with β-cyclodextrin and salt-type ionic complexes with the natural amino acid L-arginine, which contains a guanidine moiety properties necessary to create a cationic structure when interacting with phenolic groups. First, a methodology was developed for the synthesis of supromolecular structures, in which flavonoids were incorporated into a cyclodextrin matrix. As a result, the solubility in water at 20 °C of encapsulated flavonoids increased by more than two orders of magnitude. In the formation of complexes of cyclodextrin with flavonoids, the main role is played not by hydrogen bonds between the hydroxyl groups of flavonoids and β-cyclodextrin - in the case of dihydroquercetin and catechin, they are different and similar in the case of dihydroquercetin and quercetin, but the spatial orientation of the pyrocatechol cycle B (due to the flat conjugation of the entire molecule and due to sp2 is the structure of the second carbon atom of the pyran ring). Another implemented approach for obtaining water-soluble flavonoids at room temperature is the creation of their salts with the natural amino acid L-arginine, which is a part of proteins and is involved in several vital processes in the body. The structure of the obtained compounds was proved by the methods of NMR spectroscopy on 13C nuclei and X-ray structural analysis, the composition – by elemental analysis.

Applications of NMR in Drug:Cyclodextrin Complexes.

NMR spectroscopy is an effective technique, applicable for studying bioactive materials or drug delivery systems in order to obtain comprehensive details related to structural and dynamic characteristics at atomic resolution. The applications of NMR spectroscopy have been increased considerably as a result of the combination of advancement in technological NMR instrumentation and scientific knowledge. This chapter is dedicated to highlight the applications of NMR spectroscopy in drug:cyclodextrin complexes using both liquid- and solid-state NMR spectroscopy.

Electrochemistry Investigation of Drugs Encapsulated in Cyclodextrins.

The biological electron transfer reactions play an important role in the bioactivity of drugs; thus, the knowledge of their electrochemical behavior is crucial. The formation of radicals during oxidation or reduction, the presence of short-living intermediates, the determination of reaction mechanisms involving electron and proton transfers, all contribute to the comprehension of drug activities and the determination of their mode of action and their metabolites. In addition, if a drug is encapsulated in the cyclodextrin cavity, its electrochemical properties can change compared to a free drug molecule. Here we describe the combination of cyclic voltammetry, UV-Vis spectroelectrochemistry, GC-MS, HPLC-DAD, and HPLC-MS/MS as techniques for evaluating the oxidation mechanism of a drug encapsulated in the cavity of a cyclodextrin. The cavity of cyclodextrin plays a significant role in increasing the stability of the encapsulated products; therefore the identification of oxidation intermediates as semiquinone and benzofuranone derivatives of quercetin is possible in these conditions. The differences in oxidation potentials of the bioactive flavonol quercetin and its cyclodextrin complex relating to its antioxidant activity and the oxidation mechanism are herein discussed.

Formulation and Evaluation of Supramolecular Food-Grade Piperine HP β CD and TPGS Complex: Dissolution, Physicochemical Characterization, Molecular Docking, In Vitro Antioxidant Activity, and Antimicrobial Assessment.

The purpose of the present study was to improve the aqueous solubility, dissolution, and antioxidant activity of the water-insoluble drug piperine (PIP). The study was performed by preparing PIP binary inclusion complex (PIP BIC) and piperine ternary inclusion complex (PIP TIC) by different methods. The effect of a hydrophilic auxiliary substance (TPGS) was assessed with addition to PIP and hydroxypropyl beta cyclodextrin (HP β CD) complex. The phase solubility study was performed to evaluate the complexation efficiency and stability constant. The aqueous solubility, dissolution, physicochemical assessment, antioxidant activity, antimicrobial activity, and molecular docking were further evaluated to check the effect of the complexation of PIP. The stability constant (Ks) value was found to be 238 and 461 M−1 for the binary and ternary inclusion complex. The dissolution study results showed a marked enhancement of release in comparison to pure drug. XRD and SEM studies revealed the presence of more agglomerated and amorphous structures of PIP, which confirmed the formation of complexes. The results of DPPH radical scavenging and antimicrobial activity showed a significant (p < 0.05) enhancement in scavenging activity for PIP TIC (microwave irradiation (MI)). The docking studies have revealed that the binding affinity of TPGS at the PIP-HP β CD complex was −5.2 kcal/mol.

Recent Advancements and Applications of Inhalable Microparticles Based Drug Delivery Systems in Respiratory Disorders

Lower respiratory infections are the third leading cause of death, as stated by the world health organization. The pulmonary route requires reduced dose, exhibits immediate drug release, reduced first-pass hepatic metabolism and adverse effects, and systemic drug release. Therefore, an overview of recent advancements in inhalable microparticles reported in publications and patents published in the last few years has been summarized. Recent innovations in inhaler technology and major challenges in pulmonary drug delivery have been discussed briefly. The analysis was collected through comprehensive literature searches from databases such as PubMed, Google Scholar, and ScienceDirect. The recent patents on inhalable microparticles have been compiled through the PATENTSCOPE database via WIPO website. The keywords used in the search strategy were ‘inhalable microparticles’, ‘polymeric microparticles’, ‘large porous microparticles’, ‘solid lipid microparticles’, ‘cyclodextrin complex microparticles’, ‘respiratory disorders’, ‘patent, ‘inhaler technology’, ‘drug deposition’, ‘pharmacokinetic processes’ and ‘pulmonary drug delivery’ in various combinations. A survey of literature revealed that 44 publications and 14 patents, and 9 recent innovations in inhaler technology had been reported regarding inhalable microparticles in respiratory disorders. This review briefly recapitulates the pharmacokinetic processes involved in the pulmonary drug delivery route, mechanisms of drug deposition in the respiratory tract, types, and production methodology of inhalable microparticles.

A fluorescence approach on the investigation of urea derivatives interaction with a non-PET based acridinedione dye-beta Cyclodextrin (β-CD) complex in water: Hydrogen-bonding interaction or hydrophobic influences or combined effect?

Photophysical studies of resorcinol based acridinedione dyes with beta Cyclodextrin (β-CD) in the presence of urea (U) and tetramethylurea (TMU) were carried out in water. A marked variation in the absorption spectra of dye-β-CD complex was found to be more significant in the case of U rather in TMU. Interestingly, the role of urea on the excited state behavior of dye-β-CD complex is found to be entirely different from that of TMU. The formation of urea-water hydrogen-bonding self assemblies and creation of microspheres of varying environment results in an effective displacement of dye from the hydrophobic nanocavity of β-CD. On the contrary, the dye prefers a more confined hydrophobic micro environment in the presence of TMU. The nature of urea derivative, hydrogen-bonding of urea-water assemblies and hydrophobic influences of methyl moieties in urea molecular framework governs the stability and also the dissociation of dye-β-CD complex. The displacement of dye from the environment of the sugar molecule by urea derivatives is established from fluorescence studies wherein the variation in the spectral behavior of non-PET based dye-β-CD complex is found to be entirely different from that of PET dye. Both hydrogen-bonding along with hydrophobic interactions influences the excited state properties of the both PET and non-PET based acridinedione dyes are elucidated through fluorescence spectral studies. The extent of binding and the microenvironment of the dye in the presence of β-CD and urea are established through molecular docking and fluorescence anisotropy studies.

Improving the solubility of an antifungal thiazolyl hydrazone derivative by cyclodextrin complexation

RN104, named 2-[2-(cyclohexylmethylene)hydrazinyl)]-4-phenylthiazole, is a thiazolyl hydrazone derivative with promising antifungal activity. A HPLC-DAD method was carried out using C18 end-capped column (250 × 4.6 mm, 5 µm) and a mobile phase composed of water and acetonitrile (15:85 v/v) at a flow rate of 1.2 mL/min, injection volume 25 μL and DAD detection at 240 nm. The method showed to be selective, linear in the range of 20 to 240 µg/mL, precise, accurate and robust.Due to the low solubility of RN104 in water, the development of inclusion complexes using different cyclodextrins (β-CD, γ-CD and 2-HP-β-CD) was investigated, as well as the interaction mode between RN104 and cyclodextrins using molecular docking followed by semi-empirical calculations. Among tested cyclodextrins, the best results were obtained with 2-HP-β-CD, which promoted an 18-fold increase in RN104’s aqueous solubility.

The study of chiral recognition on ibuprofen enantiomers by a fluorescent probe based on β-cyclodextrin modified ZnS:Mn quantum dots

In this paper, a fluorescence method for chiral detection of ibuprofen and its enantiomer was developed. The L-cystenine-capped ZnS:Mn quantum dots were synthesized and functionalized with β-cyclodextrin (β-CD-QDs). The β-CD-QDs exhibited different quenching effect to the S-(+)-ibuprofen and the R-(-)-ibuprofen based on the advantage of the inclusion complex of cyclodextrin. It was found that the quenching of β-CD-QDs by S-(+)-ibuprofen was due to the formation of inclusion complex through both static quenching and photoinduced electron transfer, but only slight quenching with the R-(-)-ibuprofen. The stability constants derived from Hildebrand-Benesi method and absorption titration experiments were applied to determine the stability constants of the formed complexes, the double reciprocal plots suggest that a conclusion complex with a ratio of 1:1 was formed between β-CD-QDs and S-(+)-ibuprofen, but did not with the R-(-)-ibuprofen. The fluorescence intensity of the β-CD-QDs was linearly dependent on the concentration of the S-(+)-IBP in the range of 0-0.5 nmol/L with an limit of detection of 0.29 nmol/L.

Highly Enhanced Curcumin Delivery Applying Association Type Nanostructures of Block Copolymers, Cyclodextrins and Polycyclodextrins.

The limited bioavailability of the highly hydrophobic natural compound, curcumin with wide range of beneficial bioactivity is still a challenge. Self-association type systems of polyethylene oxide-polypropylene oxide-polyethylene oxide block copolymers (Pluronic) were applied to enhance the aqueous solubility of curcumin. Comparison of four Pluronics (94, 105, 127,108) with different compositions led to the conclusion that solubilization capacity is maximum for Pluronic 105 with intermediate polarity (hydrophilic/lipophilic balance (HLB) = 15) possessing the optimum balance between capacity of hydrophobic core of the micelle and hydrophilic stabilizing shell of the associate. Curcumin concentration in aqueous solution was managed to increase 105 times up to 1–3 g/L applying Pluronic at 0.01 mol/L. Formation of a host–guest complex of cyclodextrin as another way of increasing the curcumin solubility was also tested. Comparing the(2-hydroxypropyl)-α, β and γ cyclodextrins (CD) with 6, 7 and 8 sugar units and their polymers (poly-α-CD, poly-β-CD, poly-γ-CD) the γ-CD with the largest cavity found to be the most effective in curcumin encapsulation approaching the g/L range of concentration. The polymer type of the CDs presented prolonged and pH dependent release of curcumin in the gastrointestinal (GI) system modelled by simulated liquids. This retarding effect of polyCD was also shown and can be used for tuning in the combined system of Pluronic micelle and polyCD where the curcumin release was slower than from the micelle.

Certain carboxylic acid buffers can destabilize β-cyclodextrin complexes by competitive interaction.

Thirteen buffers were investigated for their effect on the binding of adamantanol to β-cyclodextrin and hydroxypropyl-β-cyclodextrin. Stability constants for the β-cyclodextrin complex ranged from 14,800 to 46,000M-1, and the binding enthalpies were between -23.2 and -10.4kJ/mole. Compared to water, the stability constant in seven carboxylic acid buffers (citric acid, maleic acid, fumaric acid, succinic acid, malonic acid, malic acid and tartaric acid) was reduced. All seven buffers exhibited a competitive mechanism. Binding constants for the interaction between β-cyclodextrin and buffers ranged from 4 to 44M-1, and binding enthalpies were in the range -19 to -11kJ/mole. There was a relation between the chemical structures of the buffers and their ability to bind to cyclodextrin. All seven buffers had a carbon chain consisting of more than three carbons in the backbone. Hydroxyl groups on the carbon chain decreased the binding affinity. 1H and ROESY NMR spectroscopy supported inclusion of the citric acid into the cyclodextrin cavity, although the results for succinic and maleic acids were ambiguous. The results demonstrated that some buffers can interact with cyclodextrin complexes, and careful considerations are necessary when choosing a buffer for cyclodextrin research.

Noncovalent Complexes of Cyclodextrin with Small Organic Molecules: Applications and Insights into Host-Guest Interactions in the Gas Phase and Condensed Phase.

Cyclodextrins (CDs) have drawn a lot of attention from the scientific communities as a model system for host–guest chemistry and also due to its variety of applications in the pharmaceutical, cosmetic, food, textile, separation science, and essential oil industries. The formation of the inclusion complexes enables these applications in the condensed phases, which have been confirmed by nuclear magnetic resonance (NMR) spectroscopy, X-ray crystallography, and other methodologies. The advent of soft ionization techniques that can transfer the solution-phase noncovalent complexes to the gas phase has allowed for extensive examination of these complexes and provides valuable insight into the principles governing the formation of gaseous noncovalent complexes. As for the CDs’ host–guest chemistry in the gas phase, there has been a controversial issue as to whether noncovalent complexes are inclusion conformers reflecting the solution-phase structure of the complex or not. In this review, the basic principles governing CD’s host–guest complex formation will be described. Applications and structures of CDs in the condensed phases will also be presented. More importantly, the experimental and theoretical evidence supporting the two opposing views for the CD–guest structures in the gas phase will be intensively reviewed. These include data obtained via mass spectrometry, ion mobility measurements, infrared multiphoton dissociation (IRMPD) spectroscopy, and density functional theory (DFT) calculations.

Electrohydrodynamic encapsulation of eugenol-cyclodextrin complexes in pullulan nanofibers

In this report, the inclusion complexes of eugenol-gamma cyclodextrin (γCD) were incorporated in pullulan nanofibers using electrospinning technique. As a control sample, the pristine eugenol contained pullulan nanofibers were electrospun, as well. The nanofibrous webs were prepared with the initial eugenol content of 12% (w/w) and pullulan/eugenol-γCD nanofibers could preserve ~93% of this volatile essential oil compound due to inclusion complexation. On the other hand, only ~23% of eugenol was preserved in case of pullulan/eugenol nanofibers. The inclusion complexation also provided an enhanced thermal stability for eugenol and its volatilization shifted from ~50-190 °C to ~125–300 °C in case of pullulan/eugenol-γCD nanofibers. The antioxidant performance of eugenol was not affected by the inclusion complexation and the nanofibers of pullulan/eugenol-γCD and pullulan/eugenol indicated ~100% and ~58% radical scavenging activity for the same nanofiber concentration (250 μm/mL). Moreover, pullulan/eugenol-γCD nanofibers maintained the antioxidant activity even after 3-months storage at room temperature (~98%) and heat-treatment performed at 175 °C for 1 h (~93%). The time dependent release test indicated that pullulan/eugenol-γCD nanofibers has a release profile in a relatively controlled manner compared to pullulan/eugenol nanofibers under the same experimental conditions. Here, the functional nanofibrous web encapsulated an essential oil compound was developed using the edible pullulan and non-toxic and natural cyclodextrin molecules. Therefore, pullulan/eugenol-γCD nanofibers can be quite a promising encapsulation and carrying matrix for the essential oils which are widely used in both food and pharmaceutical areas.

Cyclodextrin Complexation Improves the Solubility and Caco-2 Permeability of Chrysin

Chrysin is a bioflavonoid that can be found in natural products such as honey and propolis, and it possesses several biological effects such as antioxidant, anti-inflammatory, and anti-cancer activity. However, it is poorly soluble in water, and its bioavailability is limited. The aim of this research is to investigate the chrysin solubilization capacity of different β-cylcodextrin derivatives and compare their biological activities. Chrysin was complexed with β-cyclodextrin (βCD), hydroxypropyl-β-, (HPBCD) sulfobutylether-β-, (SBECD), and randomly-methylated-β-cyclodextrin (RAMEB) by the lyophilization method in 1:1 and 1:2 molar ratios. The solubilities of the chrysin–cyclodextrin complexes were tested, and the solubilization abilities of cyclodextrins were studied by phase solubility experiments. The cytotoxicity of the complexes was measured by the MTT method, and the permeability enhancement was tested on Caco-2 monolayers. The solubility study showed that the complexes formed with RAMEB had the highest solubility in water. The phase solubility experiments confirmed the strongest interaction between RAMEB and chrysin. In the viability test, none of the complexes showed cytotoxicity up to 100 µM concentration. The permeability study revealed that both at 1:1 and 1:2 ratios, the RAMEB complexes were the most effective to enhance chrysin permeability through the Caco-2 monolayers. In conclusion, cyclodextrins, especially RAMEB, are suitable for improving chrysin solubility and absorption.

β-cyclodextrin inclusion complexes with vitamin A and its esters: A comparative experimental and molecular modeling study

Cyclodextrin (CD) complexation has emerged as a promising approach for enhancing the solubility or/and stability of hydrophobic small molecule substances. Here the inclusion complexes of Vitamin A (VA), Vitamin A acetate (VAA), and Vitamin A palmitate (VAP) with β-cyclodextrin (β-CD) were prepared by co-precipitation with freeze-drying methods. Results from FT-IR, NMR, and SEM confirmed the formation of inclusion complexes. Phase solubility diagrams showed a molecular ratio of 2:1, 1:1, and 1:1 for β-CD complexes with VA, VAA, and VAP, respectively. Among these vitamins tested, free VA has the lowest thermal stability, but it was the highest after embedding with β-CD. β-CD:VA also showed a better water solubility. Although VAP achieved the highest increase rate in water solubility among the three vitamins after embedding with β-CD, water solubility of β-CD:VAP was still relatively small due to the poor water solubility of free VAP in nature. The obtained results revealed that β-CD complexation is more suitable for vitamin A than the other two vitamin A esters in promoting thermal stability and water solubility.On the basis of these experimental studies, we furthermore performed molecular docking simulations to predict possible binding mode and binding affinities of three vitamins with β-CD. Gibbs free energy changes (ΔG°) of β-CD:VA with 2:1 molecular ratio was lowest, which explained the enhanced thermal stability of VA by β-CD encapsulation. This work is useful for enlarged applications of β-CD inclusion complexes with vitamin A and its esters.

Exploring inclusion complexes of cyclodextrins with quinolinone based gastro protective drug for enhancing bioavailability and sustained dischargement

Abstract Solid rebamipide based inclusion complexes were achieved by freeze-dry method and characterized by FTIR, UV–visible, 1H-NMR, 2D-ROESY, fluorescence spectroscopy, SEM and conductance. The enzyme substituted emission spectrum of the two comparative inclusion complexes with β-cyclodextrin (β-CD) and HP-β-CD in the diverse solvent systems determined the controlled release of the drug were the mid of interest. Amylase increased the stability of the inclusion complexation, proved that if it is taken together with the inclusion complex, the effectiveness and impact of the inclusion complexes will have a prolonged effect in the body. It could significantly improve the bioavailability of rebamipide.

Conventional and nanomaterial-based techniques to increase the bioavailability of therapeutic natural products: a review

Natural products have been widely explored since ancient times to heal human diseases. Due to their biological activities and relative safety, natural products have found applications in functional foods, medicine, pharmaceuticals and nutraceuticals. However, applications are often limited by poor aqueous solubility, instability and poor bioavailability following oral administration. For instance, many natural products exhibit excellent in vitro pharmacological activity, and no or less in vivo activity as a result of poor gastrointestinal absorption. Here we review techniques and materials for bioavailability enhancement such as particle size reduction, surfactant use, pH change, solid dispersion, cyclodextrin complexation, phytosome technology, solid-lipid nanoparticles, liposome and polymeric nanoparticles. Natural substances include quercetin, naringenin, curcumin, hesperetin, andrographolide, ellagic acid, resveratrol, bilobalide sinomenine, genistein, ginkgolide and glycyrrhizin. The clinical use of piperine as bio-enhancer with rifampicin is key achievement in the treatment of tuberculosis.