Phospholipid Complex Research Articles

Complex phospholipids associate with arterial norepinephrine, non-esterified fatty acids and heart rate, markers of sympathetic nerve system in Metabolic Syndrome subjects independently of insulin resistance

Complex phospholipids associate with arterial norepinephrine, non-esterified fatty acids and heart rate, markers of sympathetic nerve system in Metabolic Syndrome subjects independently of insulin resistance

In vitro transdermal permeation and penetration properties for transfersomes of brucine

To prepare the liposomes and transfersomes of brucine, characterize their pharmaceutical properties, and compare their in vitro transdermal permeation properties. The liposomes and transfersomes of brucine were prepared by ammonium sulfate gradient method to investigate their pharmaceutical properties such as the particle size, encapsulation efficiency and deformation. The transdermal permeation properties in vitro of liposome and transfersomes from different prescriptions were compared by using modified Franz-diffustion cells with rat skin as the transdermal barrier. The results showed that the particle size of liposomes and transfersomes for brucine ranged from 100 nm to 150 nm, with even distribution for particle size. As compared with the soybean phosphatidylcholine (SPC) transfersomes, the encapsulation efficiency of complex phospholipid transfersomes was significantly improved. The deformation index of complex phospholipid transfersomes in brucine was 2.09 times and 1.76 times as much as SPC liposomes and SPC transfersomes respectively. The steady state flux of complex phospholipid transfersomes was 3.43 times and 1.41 times as much as SPC liposomes and SPC transfersomes. The steady state flux of the physical mixture of brucine and blank complex phospholipid transfersomes was 2.20 times as much as brucine solution. The concentration of complex phospholipid had effect on transdermal permeation of blank transfersomes. In conclusion, as compared with liposomes, the permeation behavior of transfersomes was significantly improved; complex phospholipid technology can improve the membrane phase behavior of transfersomes, and further improve the deformation index and transdermal flux of transfersomes; in addition, blank transfersomes have promoting effect on transdermal absorption of brucine.

Phospholipid complexation of NMITLI118RT+: way to a prudent therapeutic approach for beneficial outcomes in ischemic stroke in rats

Withania somnifera Dunal (Solanaceae) known as Ashwagandha, a popular plant of Indian origin is known to possess tremedous medicinal potential, often used as anti-inflammatory, anti-platelet, antihypertensive, hypoglycemic, hypolipidemic and adaptogenic candidate. Some of its chemotypes developed by CSIR, India includes NMITLI-101, NMITLI-118, NMITLI-128. In this study the investigators have attempted development of a phytosomal complex of NMITLI118RT + (standardized ethanolic extract of a new chemotype of W. somnifera Dunal.), its pharmaceutical characterization and evaluation of its neuro-protective potential against experimenal stroke in rats in continuation with their previous work in this area. The phytosomal complex (NIMPLC) was prepared by following a cohesive optimization design and was characterized on the basis of solubility, dissolution profile, FT-IR, DSC-TGA analysis, zeta potential, physical stability, forced degradation and photolytic degradation. Results were suggestive of a pharmaceutically acceptable formulation. NIMPLC was taken up further for biological evaluation using the middle cerebral artery occlusion (MCAO) model in rats. It could be demonstrated that the beneficial effects of NMITLI118RT + could be augmented by NIMPLC in 1 h pre and 6 h post treatment as was evident from reduction in MDA levels, increment in GSH levels, reduction in neurological deficit (ND) scores and reduction in infarct size. The study could successfully demonstrate the beneficial effects of NIMPLC in brain function restoration following stroke.

Cellular uptake and anticancer activity of salvianolic acid B phospholipid complex loaded nanoparticles in head and neck cancer and precancer cells

Salvianolic acid B (SalB) was demonstrated to be a promising chemopreventive agent for head and neck squamous cell carcinoma (HNSCC) in the previous studies by our and other research institution, but the properties like low efficacy, poor systemic delivery, and low bioavailability has hampered its clinical applications. To continue our research program focused on the use of natural compounds on cancer chemoprevention, we propose a first example of phospholipid complex loaded nanoparticles (PLC-NPs) encapsulating SalB as a potential carrier for intervention of HNSCC (HN13, HN30) cells and precancer Leuk1 cells in this study. Qualitative and quantitive studies of cellular uptake showed that intracellular accumulation of SalB was significantly higher when HN13, HN30 and Leuk1 cells were incubated with SalB-PLC-NPs complex (nano-SalB) as against free-SalB. Cell viability assay revealed that the cell growth of HN13 and HN30 cells was significantly inhibited of 56.1% and 29.3%, respectively, for nano-SalB compared to an equivalent amount of free-SalB (P<0.001). Moreover, cell cycle and apoptosis assay showed that a clear trend of cell cycle arrest and induction of apoptosis was also observed within the HNSCC cells treated with nano-SalB. Collectively, this study demonstrated that nano-SalB was significantly more potent had an anticancer effect against HNSCC cells, which serves as the first step toward establishing SalB nano-formulations as promising cancer chemopreventive agents. The current study could pave a new way for the development of drugs that target HNSCC in the future.

Anticancer effects of saponin and saponin–phospholipid complex of Panax notoginseng grown in Vietnam

ObjectiveTo evaluate the antitumor activity both in vitro and in vivo of saponin–phospholipid complex of Panax notoginseng. MethodsThe in vitro cytotoxic effect of saponins extract and saponin–phospholipid complex against human lung cancer NCI-H460 and breast cancer cell lines BT474 was examined using MTS assay. For in vivo evaluation of antitumor potential, saponin and saponin–phospholipid complex were administered orally in rats induced mammary carcinogenesis by 7,12-dimethylbenz(a)anthracene, for 30 days. ResultsOur data showed that saponin–phospholipid complex had stronger anticancer effect compared to saponin extract. The IC50 values of saponin–phospholipid complex and saponin extract for NCI-H460 cell lines were 28.47 μg/mL and 47.97 μg/mL, respectively and these values for BT474 cells were 53.18 μg/mL and 86.24 μg/mL, respectively. In vivo experiments, administration of saponin, saponin–phospholipid complex and paclitaxel (positive control) effectively suppressed 7,12-dimethylbenz(a) anthracene-induced breast cancer evidenced by a decrease in tumor volume, the reduction of lipid peroxidation level and increase in the body weight, and elevated the enzymatic antioxidant activities of superoxide dismutase, catalase, glutathione peroxidase in rat breast tissue. ConclusionsOur study suggests that saponin extract from Panax notoginseng and saponin–phospholipid complex have potential to prevent cancer, especially breast cancer.

TPGS/Phospholipids Mixed Micelles for Delivery of Icariside II to Multidrug-Resistant Breast Cancer.

The biggest challenge for the treatment of multidrug resistant cancer is to deliver a high concentration of anticancer drugs to cancer cells. Icariside II is a flavonoid from Epimedium koreanum Nakai with remarkable anticancer properties, but poor solubility and significant efflux from cancer cells limited its clinical use. In our previous study, a self-assembled mixture of micelles (TPGS–Icariside II–phospholipid complex) was successfully constructed, which could substantially increase the solubility of Icariside II and inhibit the efflux on Caco-2 cells. In this study, we evaluate the anticancer effect of the mixed micelles encapsulating Icariside II (Icar-MC) on MCF-7/ADR, a multidrug-resistant breast cancer cell line. The cellular uptake of the micelles was confirmed by fluorescent coumarin-6-loaded micelles. The IC50 of Icar-MC in MCF-7/ADR was 2-fold less than the free drug. The in vitro study showed Icar-MC induced more apoptosis and lactate dehydrogenase release. Intravenous injection of Icar-MC into nude mice bearing MCF-7/ADR xenograft resulted in a better antitumor efficacy compared with the administration of free drug, without causing significant body weight changes in mice. The antitumor effect was further verified by magnetic resonance imaging and immunohistochemical assays for Ki-67, a proliferative indicator. Moreover, Icar-MC treatment also elevated Bax/Bcl-2 ratio and the expressions of cleaved caspase-3, -8, -9 and AIFM1 in tumors. This study suggests that phospholipid/TPGS mixed micelles might be a suitable drug delivery system for Icariside II to treat multidrug resistant breast cancer.

Development of quercetin-phospholipid complex to improve the bioavailability and protection effects against carbon tetrachloride-induced hepatotoxicity in SD rats

Quercetin (QT) is a natural flavonoid with various biological activities and pharmacological actions. However, the bioavailability of QT is relatively low due to its low solubility which severely limits its use. In this study, we intended to improve the bioavailability of QT by preparing quercetin-phospholipid complex (QT-PC) and investigate the protective effect of QT-PC against carbon tetrachloride (CCl4) induced acute liver damage in Sprague-Dawley (SD) rats. The physicochemical properties of QT-PC were characterized in terms of infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD) and water/n-octanol solubility. FTIR, DSC and XRPD data confirmed the formation of QT-PC. The water solubility of QT was improved significantly in the prepared complex, indicating its increased hydrophilicity. Oral bioavailability of QT and QT-PC was evaluated in SD rats, and the plasma QT was estimated by HPLC-MS. QT-PC exhibited higher Cmax (1.58±0.11 vs. 0.67±0.08μg/mL), increased AUC0–∞ (8.60±1.25 vs. 2.41±0.51mg/Lh) and t1/2z (7.76±1.09 vs. 4.81±0.87h) when compared to free QT. The greater absorption of QT-PC group suggested the improved bioavailability. Moreover, biochemical changes and histopathological observations revealed that QT-PC provided better protection to rat liver than free QT at the same dose. Thus, phospholipid complexation might be one of the suitable approaches to improve the oral bioavailability of QT and obtain better protective effects against CCl4 induced acute liver damage in SD rats than free QT at the same dose level.

The Study of the Influence of Formulation and Process Variables on the Functional Attributes of Simvastatin–Phospholipid Complex

The aim of the present study was to examine the influence of the formulation and process variables on the entrapment efficiency of simvastatin–phospholipid complex (SPC), prepared with a goal of improving the solubility and permeability of simvastatin. The SPC was prepared using a solvent evaporation method. The influence of formulation and process variables on simvastatin entrapment was assessed using a central composite design. An additional SPC was prepared using the optimized variables from the developed quadratic model. This formulation was characterized for its physical–chemical properties. The functional attributes of the optimized SPC formulation were analyzed by apparent aqueous solubility analysis, in vitro dissolution studies, dissolution efficiency analysis, and ex vivo permeability studies. The factors studied were found to significantly influence the entrapment efficiency. The developed model was validated using the optimized levels of formulation and process variables. The physical–chemical characterization confirmed a formation of the complex. The optimized SPC demonstrated over 25-fold higher aqueous solubility of simvastatin, compared to that of pure simvastatin. The optimized SPC exhibited a significantly higher rate and extent of simvastatin dissolution (>98 %), compared to that of pure simvastatin (∼16 %). The calculated dissolution efficiency was also found to be significantly higher for the SPC (∼54 %), compared to that of pure simvastatin (∼8 %). Finally, the optimized SPC exhibited a significantly higher simvastatin permeability (>78 %), compared to that of pure simvastatin (∼11 %). The present study shows that SPC can be a promising strategy for improving the delivery of simvastatin and similar drugs with low aqueous solubility.

Curcumin: A new candidate for melanoma therapy?

Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g., BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin.

Effects of phospholipid complexes of total flavonoids from Persimmon (Diospyros kaki L.) leaves on experimental atherosclerosis rats

The total flavonoids from Persimmon leaves (PLF), extracted from the leaves of Diospyros kaki L. Dispryosl and Ebenaceae, is reported to possess many beneficial health effects. However, the oral bioavailability of PLF is relatively low due to its poor solubility. In the present study, the phospholipid complexes of total flavonoids from Persimmon leaves (PLF-PC) was prepared to enhance the oral bioavailability of PLF and to evaluate its antiatherosclerotic properties in atherosclerosis rats in comparison to PLF. A HPLC-MS method was developed and validated for the determination of quercetin and kaempferol in rats plasma to assess the oral bioavailability of PLF-PC. The effect of PLF (50mg/kg/d) and PLF-PC (equivalent to PLF 50mg/kg/d) on atherosclerosis rats induced by excessive administration of vitamin D (600,000IU/kg) and cholesterol (0.5g/kg/d) was assessed after orally administered for 4 weeks. The relative bioavailabilities of quercetin and kaempferol in PLF-PC relative to PLF were 242% and 337%, respectively. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) in serum were measured by an automatic biochemistry analyzer. The morphological changes of aorta were observed with optical microscopy. According to the levels of biochemical parameters in serum and the morphological changes of aorta, PLF-PC showed better therapeutic efficacy compared to PLF. Thus, PLF-PC holds a promising potential for increasing the oral bioavailability of PLF. Moreover, PLF-PC exerts better therapeutic potential in the treatment of atherosclerotic disease than PLF.

Solidification of magnolol phospholipid complex with polyvingypyrrolidone

In this study, magnolol phospholipid complex (MPC) was prepared and solidified with polyvingypyrrolidone (PVPP). The influence of PVPP on MPC's flowability, dissolution and oral bioavailability was investigated. The results of phase characterization using differential scanning calorimetry (DSC), infrared spectroscopy (IR), and scanning electron microscopy (SEM) showed that magnolol existed in solidified powder and MPC in an amorphous state. In flowability and dissolution experiments, solidified powder showed significant superiority. At the same time, it showed a higher oral bioavailability compared with MPC, with AUC0-∞ of 73.47 μg•h•mL⁻¹ vs. 63.48 μg•h•mL⁻¹. This process for solidifying powder with PVPP is simple and convenient.

The Significance of Anti-Beta-2-Glycoprotein I Antibodies in Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is a thrombophilic disorder that classically presents with vascular thrombosis and/or obstetric complications. APS is associated with antiphospholipid antibodies: a heterogeneous group of autoantibodies that are directed against membrane phospholipids in complex with phospholipid-binding proteins. Beta-2-glycoprotein I (B2GPI) binds anionic phospholipids and is considered to be the predominant antigen in APS and antibodies against B2GPI (anti-B2GPI) are recognised in the laboratory criteria for APS diagnosis. This review focuses on the part played by anti-B2GPI in the pathogenesis of APS, their associations with different clinical phenotypes of the disorder and new avenues for refining the diagnostic potential of anti-B2GPI testing.

Antiphospholipid antibodies detected by line immunoassay differentiate among patients with antiphospholipid syndrome, with infections and asymptomatic carriers.

BackgroundAntiphospholipid antibodies (aPL) can be detected in asymptomatic carriers and infectious patients. The aim was to investigate whether a novel line immunoassay (LIA) differentiates between antiphospholipid syndrome (APS) and asymptomatic aPL+ carriers or patients with infectious diseases (infectious diseases controls (IDC)).MethodsSixty-one patients with APS (56 primary, 22/56 with obstetric events only, and 5 secondary), 146 controls including 24 aPL+ asymptomatic carriers and 73 IDC were tested on a novel hydrophobic solid phase coated with cardiolipin (CL), phosphatic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, beta2-glycoprotein I (β2GPI), prothrombin, and annexin V. Samples were also tested by anti-CL and anti-β2GPI ELISAs and for lupus anticoagulant activity. Human monoclonal antibodies (humoAbs) against human β2GPI or PL alone were tested on the same LIA substrates in the absence or presence of human serum, purified human β2GPI or after CL-micelle absorption.ResultsComparison of LIA with the aPL-classification assays revealed good agreement for IgG/IgM aß2GPI and aCL. Anti-CL and anti-ß2GPI IgG/IgM reactivity assessed by LIA was significantly higher in patients with APS versus healthy controls and IDCs, as detected by ELISA. IgG binding to CL and ß2GPI in the LIA was significantly lower in aPL+ carriers and Venereal Disease Research Laboratory test (VDRL) + samples than in patients with APS. HumoAb against domain 1 recognized β2GPI bound to the LIA-matrix and in anionic phospholipid (PL) complexes. Absorption with CL micelles abolished the reactivity of a PL-specific humoAb but did not affect the binding of anti-β2GPI humoAbs.ConclusionsThe LIA and ELISA have good agreement in detecting aPL in APS, but the LIA differentiates patients with APS from infectious patients and asymptomatic carriers, likely through the exposure of domain 1.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1018-x) contains supplementary material, which is available to authorized users.

ApoA-IMilano phospholipid complex (ETC-216) infusion in human volunteers. Insights into the phenotypic characteristics of ApoA-IMilano carriers

Epidemiological studies support an inverse correlation between HDL-C and cardiovascular disease. However, low HDL-C levels do not always segregate with premature disease. These include, LCAT deficiency and the apolipoproteinA-IMilano (AIM) variant. AIM has a cysteine for arginine at position 173 in the otherwise cysteine free protein permitting AIM homodimerization and apoA-II heterodimerization. We relate the biochemical characteristics of low HDL-C phenotype AIM carriers to lipoprotein changes in humans administered recombinant dimeric AIM/palmitoyl-oleoyl phosphatidyl choline (ETC-216). Pharmacokinetic analysis of infused ETC-216 suggest a slow distribution of AIM into peripheral tissue and an extremely long terminal half-life in plasma. Following ETC-216 administration to normal human volunteers, an initial dose-dependent HDL-C elevation was observed. Thereafter, subjects transiently acquired a lipoprotein profile similar to that of AIM carriers, including reduced HDL-C and mild hypertriglyceridemia. The time-dependent changes in plasma lipids/lipoproteins may support an increased tissue cholesterol removing capacity of ETC-216. These findings provide mechanistic insight into the rapid removal of atheromatous plaques observed in humans, possibly linked to enhanced cholesterol removal capacity of ETC-216.

Wound Healing Effect of an in Situ Forming Hydrogel Loading Curcumin-Phospholipid Complex.

Wound is one of most commonly clinical diseases. Curcumin is known to improve wound healing but its bioavailability and therapeutic efficiency are very low. Here we firstly report the application of phospholipid complexes to wound healing. A curcumin-phospholipid complex (CPC) was prepared with a solvent-evaporation method. The X-ray diffraction showed that the CPC was amorphous, which was further demonstrated with the electron microscopy. Furthermore, the CPC was loaded into a poloxamer in situ forming hydrogel (ISG). The CPC ISG showed higher erosion rates than the curcumin ISG due to the amorphous structure of CPC, which could lead to increase in curcumin dissolution. The CPC ISG showed higher wound healing effect than the control on the rat skin wound model especially in the early phase. The epidermal recovery was highly improved by the CPC ISG compared to the control. The CPC ISG is a promising formulation as an effective wound healing dressing.

Biodistribution, hypouricemic efficacy and therapeutic mechanism of morin phospholipid complex loaded self-nanoemulsifying drug delivery systems in an experimental hyperuricemic model in rats.

This study aimed to compare the biodistribution and hypouricemic efficacy of morin and morin-phospholipid complex loaded self-nanoemulsifying drug delivery systems (MPC-SNEDDS), as well as to explore their therapeutic mechanisms. We studied the biodistribution of morin and MPC-SNEDDS after they were orally administered to rats. The hypouricemic efficacy and the therapeutic mechanisms of morin and MPC-SNEDDS were evaluated using potassium oxonate-induced hyperuricemic model in rats. With enhanced morin concentration in liver and kidney, oral delivery of MPC-SNEDDS exhibited significantly stronger urate-lowering effect in hyperuricemic rats than morin. The hypouricemic efficacy of morin was due to reduced production of uric acid via inhibiting the mRNA expression of hepatic xanthine dehydrogenase/xanthine oxidase (XDH/XO), as well as decreased urate reabsorption via modulating the alteration of mRNA levels of glucose transporter (mGLUT9), renal organic anion transporter 1 (mOAT1) and uric acid transporter (mURAT1). MPC-SNEDDS dually inhibited mRNA expression and activity of hepatic XDH/XO and restored the dysregulation of renal mGLUT9, mOAT1 and mURAT1, contributing to its superior urate-lowering efficacy. The results demonstrated the great potential of MPC-SNEDDS as an alternative oral strategy for active agents in treating hyperuricemia.

Preparation and evaluation of ziprasidone-phospholipid complex from sustained-release pellet formulation with enhanced bioavailability and no food effect.

The purpose of this work was to develop ziprasidone-phospholipid complex (ZIP-PLC) in sustained-release pellets to enhance the oral bioavailability and overcome the food effect of ziprasidone. Ziprasidone-phospholipid complex was formulated by solvent-evaporation method. The complexes were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and solubility testing. The optimized ZIP-PLC was used to prepare ZIP-PLC sustained-release pellets via extrusion-spheronization method. The pellets were characterized by in vitro drug-release studies and administered to fasted and fed beagle dogs, and their pharmacokinetics were compared with commercial formulation Zeldox capsule as a control. The results of FTIR, SEM, DSC and PXRD studies confirmed the formation of phospholipid complex. Solubility studies showed there was a higher solubility in water for ZIP-PLC than monohydrate ziprasidoe. The in vitro release rate of ziprasidone from the ZIP-PLC sustained-release pellet exhibited controlled-release characteristics with over 95% total release in 12 h. Pharmacokinetic studies in beagle dogs showed ziprasidone with prolong actions, and no food effect was achieved simultaneously in ZIP-PLC sustained-release pellet compared with Zeldox capsule. The results indicated a sustained release with prolonged actions of schizophrenia and bipolar disorder treatment.

Characterization of surfactant alterations in pigs infected with Actinobacillus pleuropneumoniae

ABSTRACTPurpose/Aim of the study: Surfactant, a surface active complex of phospholipids and proteins located at the inner surface of alveoli and small conducting airways is necessary for breathing. Bacterial respiratory tract infections frequently lead to surfactant alterations and to an increase in surface tension. Pigs, often used in experimental lung research, could suffer from severe pleuropneumonia, a highly contagious disease often characterized by sudden onset, short clinical course, high morbidity, and high mortality. It is caused by the gram-negative bacterium Actinobacillus pleuropneumoniae (A.pp.). This study tests the hypothesis that also in the subacute stage pathomorphological lung alterations are accompanied with increased inactive surfactant components. Clinical lung scores, functional and ultrastructural analysis of porcine surfactant were performed in pigs before infection and in the subacute state of infection. Clinical signs were determined using inter alia different subscores. Surfactant was isolated from the BALF for functional and quantitative ultrastructural studies. Results: In the subacute stage clinical, ultrosonographic and radiographic scores as well as the overall Respiratory Health Score showed significantly higher values than before infection. However, surfactant surprisingly contained more active surfactant subtypes and significantly less inactive subtypes such as unilamellar vesicles. The quantity of multilamellar vesicles with unclear function did not differ. The minimal surface tension of surfactant before and after infection was comparable. Conclusions: Thus, in spite of continued severe lung tissue alterations the surfactant system show signs of recovery. This may be the result of an effective adaption to inflammatory lung disorders caused by swine-specific pathogens.

Formation of Phytosome Containing Silymarin Using Thin Layer-Hydration Technique Aimed for Oral Delivery

Silymarin is a unique flavonoid complex isolated from milk thistle (Silybum marianum) and has been widely used as hepatoprotective agent. Orally administered silymarin will be absorbed rapidly and only 20-50% of silymarin will be absorbed through gastrointestinal tract, resulting on its low bioavailability. Those limitations are due to its poorly soluble either in water and oil and its low intestinal permeability. This study was aimed to develop silymarin-loaded phytosomes to improve silymarin bioavailability with sufficient safety and stability. This system consists of silymarin-phospholipid complex prepared by solvent evaporation method, which was incorporated to formed phytosome shape vesicles using thin layer method with various concentration and molar ratio of silymarin and phospholipid. Phytosome vesicles size was reduced using probe sonication. The result demonstrated that formula with 2% silymarin-phospholipid complex and molar ratio of 1:5 showed the best physical properties with mean vesicle diameter of 133.534 ± 8.76nm, polidispersity index of 0.339 ± 0.078, entrapment efficiency of 97.169 ± 2.412%, loading capacity of 12.18 ± 0.30%, and good stability after freeze thaw stability test. Analysis of FTIR spectroscopy and DSC was confirmed the presence of physical and chemical interactions between sylimarin and phospholipid complex. Well formed and discrete vesicles of phytosome were revealed by Transmission Electron Microscopy, drug content, and freeze thaw stability test.

Self-assembly of the active lactone form of a camptothecin–phospholipid complex for sustained nuclear drug delivery

(A) Illustration of the preparation of the CPT–SPC complex and its self-assembled nanoparticles (CPT–SPC NPs). (B) Illustration of drug delivery of the self-assembled CPT–SPC NPs.