Physicochemical Profiling of Baicalin Along with the Development and Characterization of Cyclodextrin Inclusion Complexes.
Jakab Géza,Bogdán Dóra,Mazák Károly,Deme Ruth,Mucsi Zoltán,Mándity István M,Noszál Béla,Kállai-Szabó Nikolett,Antal István
AAPS PharmSciTech
Baicalin is a flavone glycoside extracted from Scutellaria baicalensis, a traditional Chinese herbal medicine. Numerous pharmacological effects of baicalin were reported (e.g. antioxidant, anxiolytic); nevertheless, the most important physicochemical properties influencing the pharmacokinetic behaviour and the concomitant oral bioavailability have not yet been described in a comprehensive study. The aim of this project was to characterize the acid-base, lipophilicity, biorelevant solubility and permeability properties of the drug substance and providing scientific data to support the dosage form design. Another important objective was the comparative evaluation of six various baicalin-cyclodextrin (CD) inclusion complexes along with the creation of a suitable Drug Delivery System (DDS) for this BCS IV drug. Biorelevant profiling was carried out by NMR-pH titrations, saturation shake-flask and distribution coefficients (logP) measurements, while CD inclusion studies were fulfilled by experimental methods (phase solubility, H/C NMR, 2D ROESY) and computational approaches. Due to low aqueous solubility (67.03 ± 1.60 μg/ml) and low permeability (P = 0.037 × 10 cm/s), baicalin is classified as BCS IV. The γ-CD complexation significantly increased the solubility of baicalin (~ 5 times). The most promoted chemical shift change occurred in baicalin-γ-CD complex. Computational studies showed disparate binding pattern for baicalin in case of β- and γ-CD; furthermore, the calculated complexation energy was - 162.4 kJ mol for β-CD, while it was significantly stronger for γ-CD (- 181.5 kJ mol). The physicochemical and structural information of baicalin and its CD complexes introduced herein can create molecular basis for a promising DDS with enhanced bioavailability containing a bioactive phytopharmacon.
10.1208/s12249-019-1525-6
In-Depth Study of Cyclodextrin Complexation with Carotenoids toward the Formation of Enhanced Delivery Systems.
Clercq Sébastien,Temelli Feral,Badens Elisabeth
Molecular pharmaceutics
The goal of this study was molecular modeling of cyclodextrin (CD) and carotenoid complex formation. Distinction was made between complexes resulting from interactions between carotenoids and either molecularly dispersed CDs or solid crystalline CDs, considering that both cases can occur depending on the complex formation process pathways. First, the formation of complexes from dispersed CD molecules was investigated considering five different CDs (αCD, βCD, methyl-βCD, hydroxypropyl-βCD, and γCD) and lutein, as a model carotenoid molecule. The interactions involved and the stability of the different complexes formed were evaluated according to the CD size and steric hindrance. Second, the formation of complexes between four different crystalline CDs (βCD with three different water contents and methyl-βCD) and three carotenoid molecules (lutein, lycopene, and β-carotene) was studied. The docking/adsorption of the carotenoid molecules was modeled on the different faces of the CD crystals. The findings highlight that all the CD faces, and thus their growth rates, were equally impacted by the adsorption of the carotenoids. This is due to the fact that all the CD faces are exhibiting similar chemical compositions, the three studied carotenoid molecules are rather chemically similar, and last, the water-carotenoid interactions appear to be weak compared to the CD-carotenoid interactions.
10.1021/acs.molpharmaceut.0c01227
A Comparative Study on Anti-Invasion, Antimigration, and Antiadhesion Effects of the Bioactive Carotenoids of Saffron on 4T1 Breast Cancer Cells Through Their Effects on Wnt/β-Catenin Pathway Genes.
Arzi Laleh,Riazi Gholamhossein,Sadeghizadeh Majid,Hoshyar Reyhane,Jafarzadeh Nazli
DNA and cell biology
Crocus sativus L. (saffron) has been used as a spice and as a medicine for the past four thousand years. Recently, saffron has been well documented to possess anticancer effects on primary tumors. However studies of its antimetastatic potential are lacking. The present study is a comparative investigation of the antimetastatic effects of saffron carotenoids, crocin and crocetin, on triple negative metastatic breast cancer cells (4T1) and their effects on the Wnt/β-catenin pathway. It was found that treatment of 4T1 cells with crocin and crocetin resulted in the inhibition of viability in a dose-dependent manner. Scratch and Transwell chamber assays showed that the nontoxic doses of crocin and crocetin significantly inhibited migration, cell mobility, and invasion, also attenuating adhesion to extracellular matrix. Crocin downregulated mRNA expression of FZD7, NEDD9, VIM, and VEGF-α genes and upregulated E-CAD. Crocin and crocetin exhibited comparable anti-invasion properties on 4T1 cells. However, crocin and crocetin exerted more pronounced antimigration and antiadhesion potency, respectively. Furthermore, we showed that the antimetastatic effects of crocin can occur through interfering with the Wnt/β-catenin pathway.
10.1089/dna.2018.4248
Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53-dependent and -independent mechanisms.
Zhong Ying-jia,Shi Fang,Zheng Xue-lian,Wang Qiong,Yang Lan,Sun Hong,He Fan,Zhang Lin,Lin Yong,Qin Yong,Liao Lin-chuan,Wang Xia
Acta pharmacologica Sinica
AIM:To investigate the anticancer effect of crocetin, a major ingredient in saffron, and its underlying mechanisms. METHODS:Cervical cancer cell line HeLa, non-small cell lung cancer cell line A549 and ovarian cancer cell line SKOV3 were treated with crocetin alone or in combination with vincristine. Cell proliferation was examined using MTT assay. Cell cycle distribution and sub-G(1) fraction were analyzed using flow cytometric analysis after propidium iodide staining. Apoptosis was detected using the Annexin V-FITC Apoptosis Detection Kit with flow cytometry. Cell death was measured based on the release of lactate dehydrogenase (LDH). The expression levels of p53 and p21(WAF1/Cip1) as well as caspase activation were examined using Western blot analysis. RESULTS:Treatment of the 3 types of cancer cells with crocetin (60-240 μmol/L) for 48 h significantly inhibited their proliferation in a concentration-dependent manner. Crocetin (240 μmol/L) significantly induced cell cycle arrest through p53-dependent and -independent mechanisms accompanied with p21(WAF1/Cip1) induction. Crocetin (120-240 μmol/L) caused cytotoxicity in the 3 types of cancer cells by enhancing apoptosis in a time-dependent manner. In the 3 types of cancer cells, crocetin (60 μmol/L) significantly enhanced the cytotoxicity induced by vincristine (1 μmol/L). Furthermore, this synergistic effect was also detected in the vincristine-resistant breast cancer cell line MCF-7/VCR. CONCLUSION:Ccrocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug or as a chemosensitizer for vincristine.
10.1038/aps.2011.109
Crocetin and crocin decreased cholesterol and triglyceride content of both breast cancer tumors and cell lines.
Avicenna journal of phytomedicine
OBJECTIVE:Inhibition of lipid metabolism in breast cancer has been suggested as an effective approach for cancer therapy. Saffron-derived crocetin (Crt) and crocin (Cro) with the known anticancer activity, have shown hypolipidemic effect in diabetes and atherosclerosis. Here, we investigated the effect of Crt/Cro on lipid content in breast cancer. MATERIALS AND METHODS:A multi-model approach involving and studies was applied. The 4T1-induced breast cancer in mice was used to investigate the effect of Crt/Cro on cholesterol (Chl) and triglyceride (TG) levels in serum and tumor tissues. The Chl/TG levels were also assessed in the cytosol of MDA-MB-231 and MCF-7 breast cancer cell lines 6, 12 and 24 hr after Crt/Cro treatment. The interaction between Crt/Cro and hydroxymethylglutaryl coenzyme A reductase (HMGCR) was also computed by docking analysis. RESULTS:Crt reduced both serum (p=0.003) and tumor (p=0.011) Chl and TG (p=0.001) levels in mice. Cro reduced TG levels in tumor (p=0.014) and serum (p=0.002) and Chl level in tumor (p=0.013) tissues. Crt reduced both Chl and TG in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Cro reduced both Chl and TG in MDA-MB-231 (p=0.014 and p=0.002, respectively) and MCF-7 (p=0.014 and p=0.002, respectively), after 24 h. Crt binds to the active site of HMGCR with higher affinity (ΔG=-6.6 kcal/mol) than simvastatin (ΔG =-6.0 kcal/mol). CONCLUSION:Crt and Cro effectively decreased Chl/TG content in the sera of tumor bearing mice, in breast tumors and breast cancer cell lines. Crt showed a higher hypolipidemic potential than Cro. analysis indicated Crt binding in the HMGCR active site.
Comparative anticancer activity analysis of saffron extracts and a principle component, crocetin for prevention and treatment of human malignancies.
Journal of food science and technology
ABSTRACT:Saffron, obtained from dry stigmas of the flowers of L. (fam. Iridaceae), is an ancient spice and a natural food colorant that has been used to treat various diseases in the long human history. Crocetin is of the main secondary metabolites of saffron and its curative properties for many ailments have been revealed in the previous scientific reports. The aim of this study was to evaluate the anticancer potentials of saffron extracts and its pure crocetin compounds against human cancer cells. The cytotoxic and antiproliferative activities along with lactate dehydrogenase activities of extracts and crocetin, a carotenoid derived from saffron, were assessed using A549, MCF-7 and HeLa human cancer cells, and compared to the non-malignant HUVECs. Additionally, apoptotic activity in the cells treated and untreated with the extracts and pure crocetin were determined in terms of DNA fragmentation. The results showed the extracts and crocetin from saffron induced cytotoxicity, enhanced cancer cell death as well as inhibited cancer cell growth in a concentration and time dependent manner. In addition, the results revealed that the tested compounds at different concentration had no cytotoxic effects on the non-malignant cells, whereas, it could significantly decrease the cell viability and proliferation in the malignant cells. As compared to anticancer potentials of the analyzed extracts and its pure crocetin compounds, crocetin was found as the more potent one. Overall, this research suggests that crocetin is a potential anticancer agent that can be used for cancer prevention and treatment. GRAPHIC ABSTRACT:
10.1007/s13197-019-04014-y
Evaluation of anti-cancer activity of PLGA nanoparticles containing crocetin.
Hafezi Ghahestani Zohreh,Alebooye Langroodi Fatemeh,Mokhtarzadeh Ahad,Ramezani Mohammad,Hashemi Maryam
Artificial cells, nanomedicine, and biotechnology
Poor solubility of crocetin has limited its use as a potential chemotherapeutic agent. In this study, a crocetin nanocarrier was formulated based on poly(lactic-co-glycolic acid) (PLGA) polymer. The effect of preparation conditions on the size and entrap efficiency of PLGA nanoparticles (NPs) via single emulsion/solvent evaporation method was evaluated. Cytotoxicity of crocetin and crocetin-encapsulated PLGA NPs was assayed in MCF-7 cell line. In PLGA formulations, the optimal condition was found to be 5% polyvinyl alcohol (PVA), crocetin:polymer ratio 1:20 and dichloromethane as organic solvent. Obtained results demonstrated that the encapsulation of crocetin in PLGA significantly increased the cytotoxicity of this compound.
10.1080/21691401.2016.1198359
[Pharmacokinetics of crocetin in rats].
Liu Tong-zheng,Qian Zhi-yu
Yao xue xue bao = Acta pharmaceutica Sinica
AIM:To develop an HPLC method for the determination of crocetin in rat plasma and study the pharmacokinetics in rats. METHODS:Hypersil C18 column (5 microns, 4.6 mm x 200 mm) was used at column temperature 30 degrees C. The mobile phase consisted of methanol-water-acetic acid (75:24.5:0.5) at the flow rate of 1.0 mL.min-1. The UV detection wave length was 423 nm. RESULTS:The calibration curve was linear (gamma = 0.9996) in the range from 0.49 microgram.mL-1 to 7.87 micrograms.mL-1 for crocetin. The mean recovery was 105.2%. The lowest detectable concentration of crocetin was 0.14 microgram.mL-1 (S/N = 3). The RSDs of within-day and between-day were all less than 5%. The plasma crocetin was steady. The HPLC method of determination of crocetin in the plasma was established. After single dose of 50 mg.kg-1 ig in 10 rats, the main pharmacokinetic parameters were estimated as follows: T1/2 alpha (30 +/- 6) min, Tmax(65 +/- 16) min, Cmax(5.0 +/- 1.0) microgram.mL-1, AUC0-T(845 +/- 109) microgram.min.mL-1, Vd(5.0 +/- 0.8) L.kg-1. Crocetin was shown to be absorbed into the blood through the gastrointestinal tract. CONCLUSION:This method is quick, precise and reliable. Crocetin was shown to be quickly absorbed in rats.
Preparation, chemical characterization and determination of crocetin's pharmacokinetics after oral and intravenous administration of saffron (Crocus sativus L.) aqueous extract to C57/BL6J mice.
Christodoulou Eirini,Grafakou Maria-Eleni,Skaltsa Eleni,Kadoglou Nikolaos,Kostomitsopoulos Nikolaos,Valsami Georgia
The Journal of pharmacy and pharmacology
OBJECTIVES:To prepare a lyophilized saffron aqueous extract (SFE) and determine its chemical profile and serum and tissue pharmacokinetics after intravenous and oral administration to C57/Bl6J mice. METHODS:Lyophilized SFE was prepared, characterized using semi-preparative HPLC and NMR analysis, and stability studies at room temperature, and was quantified for crocin content with an HPLC-PDA method. After intravenous and oral administration of SFE (60 mg/kg, reconstituted with water for injection) to C57/Bl6J mice, crocetin (derived from in vivo crocin hydrolysis) serum and tissue levels (unconjugated and total) were measured with an HPLC-PDA method and subjected to compartmental and non-compartmental PK analysis. KEY FINDINGS:Saffron aqueous extract was rich in all-trans-crocin (27.8 ± 0.1% w/w) and stable for more than 15 months. One-compartment PK model described crocetin's (unconjugated) kinetics after intravenous administration of SFE, while a first-order kinetic parameter described the rate of crocetin biotransformation to crocetin metabolite (conjugated). Α οne-compartment PK model with first-order absorption described crocetin and crocetin's metabolite kinetics after SFE oral administration. Relative oral bioavailability was calculated at 1.17 for total crocetin. Tissue NCA PK analysis revealed extensive crocetin distribution to liver and kidneys. CONCLUSIONS:SFE is a stable lyophilized extract rich in all-trans-crocin. The PK study allowed the estimation of basic PK parameters and the bioavailability of SFE's main bioactive component, crocetin, after peros administration.
10.1111/jphp.13055
Development and Validation of HPLC Method for Determination of Crocetin, a constituent of Saffron, in Human Serum Samples.
Mohammadpour Amir Hooshang,Ramezani Mohammad,Tavakoli Anaraki Nasim,Malaekeh-Nikouei Bizhan,Amel Farzad Sara,Hosseinzadeh Hossein
Iranian journal of basic medical sciences
OBJECTIVE(S):The present study reports the development and validation of a sensitive and rapid extraction method beside high performance liquid chromatographic method for the determination of crocetin in human serum. MATERIALS AND METHODS:The HPLC method was carried out by using a C18 reversed-phase column and a mobile phase composed of methanol/water/acetic acid (85:14.5:0.5 v/v/v) at the flow rate of 0.8 ml/min. The UV detector was set at 423 nm and 13-cis retinoic acid was used as the internal standard. Serum samples were pretreated with solid-phase extraction using Bond Elut C18 (200mg) cartridges or with direct precipitation using acetonitrile. RESULTS:The calibration curves were linear over the range of 0.05-1.25 µg/ml for direct precipitation method and 0.5-5 µg/ml for solid-phase extraction. The mean recoveries of crocetin over a concentration range of 0.05-5 µg/ml serum for direct precipitation method and 0.5-5 µg/ml for solid-phase extraction were above 70 % and 60 %, respectively. The intraday coefficients of variation were 0.37- 2.6% for direct precipitation method and 0.64 - 5.43% for solid-phase extraction. The inter day coefficients of variation were 1.69 - 6.03% for direct precipitation method and 5.13-12.74% for solid-phase extraction, respectively. The lower limit of quantification for crocetin was 0.05 µg/ml for direct precipitation method and 0.5 µg/ml for solid-phase extraction. CONCLUSION:The validated direct precipitation method for HPLC satisfied all of the criteria that were necessary for a bioanalytical method and could reliably quantitate crocetin in human serum for future clinical pharmacokinetic study.
The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.
Umigai N,Murakami K,Ulit M V,Antonio L S,Shirotori M,Morikawa H,Nakano T
Phytomedicine : international journal of phytotherapy and phytopharmacology
Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as β-carotene, lutein and lycopene.
10.1016/j.phymed.2010.10.019
Dimethyl-β-cyclodextrin/salazosulfapyridine inclusion complex-loaded chitosan nanoparticles for sustained release.
Tang Peixiao,Yang Hongqin,Tang Bin,Wu Di,Du Qiaohong,Xu Kailin,Li Hui
Carbohydrate polymers
This study aimed to investigate a novel delivery system for salazosulfapyridine (SASP) through encapsulation in 2,6-dimethyl-β-cyclodextrin (DMβCD) and further incorporation in chitosan (CS) to form nanoparticles (NPs). The inclusion complex of SASP and DMβCD was prepared at 1:1 host-guest stoichiometry based on Job's plot and then characterized through various analytical techniques. Then, the DMβCD/SASP inclusion complex was incorporated in CS to form DMβCD/SASP/CS NPs. The loading efficiency of SASP in the DMβCD/SASP/CS NPs was significantly higher than that of the SASP/CS NPs. A positive zeta potential of +35.4mV was also observed in the DMβCD/SASP/CS NPs with an average size of 90nm. SASP exhibited a sustained release after the DMβCD/SASP/CS NPs were formed. The toxicity of the NPs to LO2 cells was lower than that of free SASP. Therefore, the CD inclusion complex-loaded CS NPs can be applied to deliver hydrophobic drugs.
10.1016/j.carbpol.2016.09.038
Inclusion Complexes of Citronella Oil with -Cyclodextrin for Controlled Release in Biofunctional Textiles.
Lis Manuel J,García Carmona Óscar,García Carmona Carlos,Maestá Bezerra Fabricio
Polymers
Biofunctional textiles with integrated drug-delivery systems can help in the fight against vector-borne diseases. The use of repellent agents derived from plants and oils is an alternative to DEET (,-diethyl--methylbenzamide), which has disadvantages that include toxic reactions and skin damage. However, some researchers report that oils can be ineffective due to reasons related to uncontrolled release. In this work, the mechanism of control of citronella oil (OC) complexed with -cyclodextrin (CD) on cotton (COT) and polyester (PES) textiles was investigated. The results obtained reveal that finishing cotton and polyester with -cyclodextrin complexes allows for control of the release mechanism of the drug from the fabric. To assess the complexes formed, optical microscopy, SEM, and FTIR were carried out; the yield of complex formation was obtained by spectroscopy in the ultraviolet region; and controlled release was performed in vitro. Oil complexation with CD had a yield of 63.79%, and it was observed that the release, which was in seconds, moved to hours when applied to fabrics. The results show that complexes seem to be a promising basis when it comes to immobilizing oils and controlling their release when modified with chemical crosslinking agents.
10.3390/polym10121324
Improved Pharmacokinetics of Aceclofenac Immediate Release Tablets Incorporating its Inclusion Complex with Hydroxypropyl-β-Cyclodextrin.
Dahiya Sunita,Kaushik Atul,Pathak Kamla
Scientia pharmaceutica
The present investigation reports the various pharmacokinetic parameters of immediate release aceclofenac tablets incorporating its inclusion complex with hydroxypropyl-β-cyclodextrin. The tablets were prepared using aceclofenac: hydroxypropyl-β-cyclodextrin in a 1:1 molar ratio by the direct compression method (TKN). The results were compared with those of the marketed brand (MKT) and pure drug (TAC). The P-values indicated that mean plasma concentrations were significantly different among all three formulations administered (P<0.05, P<0.01). TKN showed significantly higher plasma levels when compared to the pure drug (P<0.01). The Cmax and AUC(0-∞) of TKN were significantly higher (P<0.05) compared to the pure drug and marketed formulation. Furthermore, the first-order overall elimination rate constant (Kel) of TKN was also significantly higher (P<0.05) compared to the pure drug and its marketed formulation. These results suggested that tablets prepared by incorporating the AC-HPβCD inclusion complex (TKN) would provide a more rapid onset of pharmacological effects in comparison to the marketed formulation and pure drug.
10.3797/scipharm.1509-07
Docetaxel/2-Hydroxypropyl β -Cyclodextrin Inclusion Complex Increases Docetaxel Solubility and Release from a Nanochannel Drug Delivery System.
Ferrati Silvia,Nicolov Eugenia,Bansal Shyam,Hosali Sharath,Landis Melissa,Grattoni Alessandro
Current drug targets
Breast cancer remains the second leading cause of cancer deaths for women in the U.S. The need for new and alternative strategies to treat this cancer is imperative. Here we show the optimization of our nanochannel delivery system (nDS) for constant and sustained delivery of docetaxel (DTX) for thetreatment of triple negative breast cancer. DTX is a highly hydrophobic drug, making it difficult to reach the therapeutic levels when released in aqueous solutions from our implantable delivery system. To overcome this challenge and test the release of DTX from nDS, we prepared DTX/2-hydroxypropyl β-cyclodextrin (DTX/HPCD) inclusion complexes in different molar ratios. The 1:10 DTX/HPCD complex achieved 5 times higher solubility than the 1:2 complex and 3 times higher in vitrorelease of DTX than with free DTX. When released in SCID/Beige mice from nanochannel system, the DTX/HPCD complex showed reduced tumor growth, comparable to the standard bolus injections of DTX, indicating that the structural stability and biological activity of DTX were retained in the complex, after its diffusion through the nanochannel system.
Preparation, release and physicochemical characterisation of ethyl butyrate and hexanal inclusion complexes with β- and γ-cyclodextrin.
Zhang Yang,Zhou Yibin,Cao Shengnan,Li Songnan,Jin Shanshan,Zhang Shu
Journal of microencapsulation
Complexes of ethyl butyrate and hexanal encapsulated by β-cyclodextrin (β-CD) and γ-cyclodextrin (γ-CD) were prepared by coprecipitation, and gas chromatography was used to quantity the flavour compounds in the complexes. The ethyl butyrate-γ-CD complex had the highest inclusion ratio (12.20%) followed by the ethyl butyrate-β-CD, hexanal-β-CD and hexanal-γ-CD complexes (11.29, 4.41 and 3.33%, respectively). Release experiments were performed under different relative humidities (RH 93, 75 and 52%) and temperatures (4 and 25 °C). The flavour release behaviours of the complexes were described by the Avrami equation. The rate of flavour release was enhanced with both increasing temperature and RH, although the effect of RH was stronger. Physicochemical characterisation using FT-IR, XRD, DSC and SEM analyses demonstrated that crystalline complexes were formed. Both β-CD and γ-CD were able to encapsulate ethyl butyrate and hexanal, and lower RH and temperature were more suitable for the storage of these complexes.
10.3109/02652048.2015.1073391
Controlled-release drug delivery system based on fluocinolone acetonide-cyclodextrin inclusion complex incorporated in multivesicular liposomes.
Vafaei Seyed Yaser,Dinarvand Rassoul,Esmaeili Motahareh,Mahjub Reza,Toliyat Tayebeh
Pharmaceutical development and technology
Multivesicular liposomes (MVLs) have been widely studied for encapsulation of hydrophilic drugs due to their structural properties and large aqueous inner cavities. In this study, to investigate MVLs and their potential application for incorporation of hydrophobic drugs, new drug delivery system for fluocinolone acetonide (FA), as a lipophilic model drug, was developed combining the advantages of cyclodextrin inclusion complexes (CD-IC) and multivesicular liposomes. FA was complexed with several CDs to form inclusion complex (FA-CD-IC) and then FA-CD-IC was incorporated into MVLs by reverse-phase evaporation method. Physicochemical characterization of drug-CD-IC, at a molar ratio of 1:1 (drug to CD) was studied using HNMR, FT-IR, DSC and UV spectroscopy. The influence of various types of CDs on the aqueous solubility of FA, encapsulation efficiency and release profile in MVLs was studied. The results revealed the formation of inclusion complexes between the drug and CDs. Both the CD's type and proportion played an important role in the physicochemical properties of the systems. The inclusion complex of the drug with hydroxypropyl-β-cyclodextrin exhibited the most appropriate loading and sustained-release profile over prolonged periods. The results reveal the promising potential of MVLs as a stable drug delivery system to release the drug in a sustained manner for the treatment of ocular inflammatory disease.
10.3109/10837450.2014.920358
Preparation, physicochemical characterization and release behavior of the inclusion complex of trans-anethole and β-cyclodextrin.
Zhang Wenwen,Li Xinying,Yu Taocheng,Yuan Lun,Rao Gang,Li Defu,Mu Changdao
Food research international (Ottawa, Ont.)
Trans-anethole (AT) has a variety of antimicrobial properties and is widely used as food functional ingredient. However, the applications of AT are limited due to its low water solubility, strong odor and low physicochemical stability. Therefore, the aim of this work was to encapsulate AT with β-cyclodextrin (β-CD) for obtaining inclusion complex by co-precipitation method. The measurements effectively confirmed the formation of inclusion complex between AT and β-CD. The results showed that the inclusion complex presented new solid crystalline phases and was more thermally stable than the physical mixture and β-CD. The phase solubility study showed that the aqueous solubility of AT was increased by being included in β-CD. The calculated stability constant of inclusion complex was 1195M, indicating the strong interaction between AT and β-CD. Furthermore, the release study suggested that β-CD provided the protection for AT against evaporation. The release behavior of AT from the inclusion complex was controlled.
10.1016/j.foodres.2015.04.029
Effect of inclusion complexation of meloxicam with β-cyclodextrin- and β-cyclodextrin-based nanosponges on solubility, in vitro release and stability studies.
Shende Pravin K,Gaud R S,Bakal Ravindra,Patil Dipmala
Colloids and surfaces. B, Biointerfaces
The objective of the present work was to develop inclusion complexes of meloxicam with β-cyclodextrin- and β-cyclodextrin-based nanosponges to enhance their solubility and stability and to prolong release using different methods that included physical mixing, kneading and sonication. Particle size, zeta potential, encapsulation efficiency, stability study results, in vitro and in vivo drug release study results, FTIR, DSC and XRPD were used as characterization parameters. SEM (Scanning Electron Microscope) studies revealed that the particle sizes of the inclusion complexes of meloxicam were within the range of 350 ± 5.69-765 ± 13.29 nm. The zeta potentials were sufficiently high to obtain stable formulations. In vitro and in vivo release studies revealed the controlled release of meloxicam from the nanosponges for 24h. The interaction of the meloxicam with the nanosponges was confirmed by FTIR and DSC. A XRPD study revealed that the crystalline nature of meloxicam was changed to an amorphous form due to the complexation with the nanosponges. A stability study revealed that the meloxicam nanosponges were stable. Therefore, β-cyclodextrin-based nanosponges represent a novel approach for the controlled release of meloxicam for anti-inflammatory and analgesic effects.
10.1016/j.colsurfb.2015.09.002
In Vitro Dissolution Studies of Amiodarone Hydrochloride From Hydroxy-Propyl-β-Cyclodextrin/Amiodarone Inclusion Complex Formulated Into Modified-Release Tablets.
Creţeanu Andreea,Ochiuz Lăcrămioara,Vieriu Mădălina,Panainte Alina Diana,Ţântaru Gladiola
Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi
Aim:Drug release from modified-release matrix tablets made of Kollidon® SR and Chitosan is dependent on its degree of solubility in the dissolution medium as well as on the matrix forming polymer. By complexing hydrochloride amiodarone with hydroxypropyl-β-cyclodextrin, an inclusion complex was obtained, which showed an increase in solubility by more than 200%. The complex was used to obtain modified-release matrix tablets based on Kollidon® SR and Chitosan. Materials and Methods:Matrix tablets were obtained through direct compression method of non-complexed amiodarone and inclusion complex, and they were marked F1 and F10, respectively. The two formulations were studied comparatively in terms of release kinetics of the active substance through in vitro drug release tests. Those tests were conducted using a paddle apparatus II for 12 hours and two gastrointestinal simulation liquids with different pH values relevant for oral administration - 2 hours at pH 1.2 and 10 hours at pH 6.8. The release of hydrochloride amiodarone was quantified using a validated HPLC method. Two factors were calculated to assess the release profile of amiodarone: the similarity factor f1 and difference factor f2. Results:The increase in Kollidon® SR concentration resulted in a slower release of amiodarone at both pH values. The use of Chitosan resulted in a decrease of AMD release only at pH 6.8. Conclusions:The similarities between the two release profiles of AMD were confirmed by the values of the similarity factor (f1 = 43.697) and difference factor f2 (f2 = 68.263).