Combination of Phospholipid Complex and Matrix Dispersion.

Phospholipid complexation, despite being a successful, versatile, and burgeoning strategy, stickiness of phospholipids leads to suboptimal dissolution rate of drugs. This work was undertaken to fabricate simvastatin-phospholipid complex (SIM-PLC)-loaded matrix dispersion (SIM-PLC-MD) using Soluplus® as carrier material, to augment dispersibility and dissolution of SIM-PLC without altering complexation between simvastatin (SIM) and phospholipid. SIM-PLC and SIM-PLC-MD were prepared using solvent evaporation and discontinuous solvent evaporation techniques, respectively. The successful complexation was substantiated by FTIR method. Besides, PXRD and SEM studies disclosed the absence of crystallinity of SIM in both SIM-PLC and SIM-PLC-MD. The TEM analysis monitored the self-assembly of SIM-PLC and SIM-PLC-MD into colloidal structures, which could be correlated with redispersion in GIT fluids upon oral administration. The considerable increase in hydrophilicity of SIM-PLC-MD and SIM-PLC as evident from partition coefficient experiment can further be correlated with their remarkably improved solubility profiles in the following pattern: SIM-PLC-MD˃SIM-PLC˃SIM. Correspondingly, improved dispersibility of SIM-PLC-MD in comparison to SIM-PLC can be accountable for accelerated dissolution rate by 2.53-fold and 1.5-fold in pH 1.2 and 6.8 conditions, respectively. The oral pharmacokinetic evaluation in Sprague Dawley (SD) rats revealed 3.19-fold enhancement in oral bioavailability of SIM through SIM-PLC-MD when compared with plain SIM, whereas 1.83-fold increment was observed in the case of SIM-PLC. Finally, the efficacy experimentation in SD rats revealed that SIM-PLC-MD significantly reduced triglycerides and cholesterol levels in comparison to SIM and SIM-PLC. These outcomes suggest that a matrix dispersion strategy improves oral bioavailability and hypolipidemic activity of SIM.

Intravasation Affects the Diagnostic Image Quality of Transvaginal 4-Dimensional Hysterosalpingo-Contrast Sonography With SonoVue.

OBJECTIVES: We aim to retrospectively analyze the diagnostic image quality of transvaginal 4-dimensional hysterosalpingo-contrast sonography from infertile patients and determine the significant influencing factors. METHODS: A total of 445 patients visiting infertility clinics were included in the study, of which 167 were primary infertile and 278 were secondary infertile. The factors were recorded, including age; examination time; infertility type; history of pelvic inflammatory disease, pelvic surgery, intrauterine surgery, and ectopic pregnancy; endometrial thickness; uterine position; ovarian position; 2-dimensional image quality; intravasation quantity, position, and time; balloon volume; and the dosage of contrast agent or the sterile saline solution. All the factors were compared among different diagnostic image quality groups. The method of rank logistic regression analysis was adopted to analyze the risk factors affecting the diagnostic image quality. RESULTS: Among the 445 infertile patients, 124 (27.9%) patients had intravasation occur during transvaginal 4-dimensional hysterosalpingo-contrast sonography. The diagnostic image quality between the 2 sonographers was consistent (Cronbach's alpha, 0.993). Different intravasation quantities, positions, and times; increased of balloon volume; and history of pelvic surgery were substantial risk factors for the diagnostic image quality. The diagnostic image quality diminished with the increase of intravasation. In the patient with cornual intravasation, the diagnostic image quality was substantially worse than that with non-cornual intravasation. Moreover, early onset of intravasation seriously affected the diagnostic image quality. CONCLUSIONS: In conclusion, intravasation affected the diagnostic image quality, especially early cornual massive intravasation.

Thymoquinone-loaded lipid vesicles: a promising nanomedicine for psoriasis.

BACKGROUND: Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model. METHODS: TQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis. RESULTS: The spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation. CONCLUSIONS: The promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.

Systematically Optimized Imiquimod-Loaded Novel Hybrid Vesicles by Employing Design of Experiment (DoE) Approach with Improved Biocompatibility, Stability, and Dermatokinetic Profile.

The present research work explored the possibility of harnessing the benefits of vesicular carriers for overcoming imiquimod-associated complaints or side effects. Hybrid vesicles were prepared by the most common and easily scalable method, i.e., thin film hydration. The chaffing of myriad of factors, both process and material related, affecting the desirable attributes of conceived vesicles, was performed through Taguchi design. Based upon the analysis of Pareto chart and prior experiences, concentration of phospholipid and poloxamer 407 was selected for optimization by 2 levels, 13 run central composite design (CCD). The optimized hybrid vesicles contained 1% w/v phospholipid and 3% w/v poloxamer 407. The optimized hybrid vesicles were incorporated into the 3% w/v carbopol 940 gel and characterized for morphology, physicochemical properties, and rheological behavior. The release (%) and skin retention (% of total dose) across rat skin from gel at same amount of formulation was more than Imiquad®. The gel delivered the loaded cargo, preferably, in the viable region of skin and formed local depot in confocal microscopic studies. The gel followed one compartment open body dermatokinetic model in rat skin. There was not any harmful effect on the mice skin after repeated applications. The gel was stable at room conditions for 1 year.

Acoustic Characterization and Enhanced Ultrasound Imaging of Long-Circulating Lipid-Coated Microbubbles.

OBJECTIVES: A long-circulating lipid-coated ultrasound (US) contrast agent was fabricated to achieve a longer wash-out time and gain more resistance against higher-mechanical index sonication. Systemic physical, acoustic, and in vivo imaging experiments were performed to better understand the underlying mechanism enabling the improvement of contrast agent performance by adjusting the physical and acoustic properties of contrast agent microbubbles. METHODS: By simply altering the gas core, a kind of US contrast agent microbubble was synthesized with a similar lipid-coating shell as SonoVue microbubbles (Bracco SpA, Milan, Italy) to achieve a longer wash-out time and higher inertial cavitation threshold. To bridge the structure-performance relationship of the synthesized microbubbles, the imaging performance of the microbubbles was assessed in vivo with SonoVue as a control group. The size distribution and inertial cavitation threshold of the synthesized microbubbles were characterized, and the shell parameters of the microbubbles were determined by acoustic attenuation measurements. All of the measurements were compared with SonoVue microbubbles. RESULTS: The synthesized microbubbles had a spherical shape, a smooth, consistent membrane, and a uniform distribution, with an average diameter of 1.484 µm. According to the measured attenuation curve, the synthesized microbubbles resonated at around 2.8 MHz. Although the bubble's shell elasticity (0.2 ± 0.09 N/m) was comparable with SonoVue, it had relatively greater viscosity and inertial cavitation because of the different gas core. Imaging studies showed that the synthesized microbubbles had a longer circulation time and a better chance of fighting against rapid collapse than SonoVue. CONCLUSIONS: Nano/micrometer long-circulating lipid-coated microbubbles could be fabricated by simply altering the core composition of SonoVue microbubbles with a higher-molecular weight gas. The smaller diameter and higher inertial cavitation threshold of the synthesized microbubbles might make it easier to access deep-seated organs and give prolonged imaging enhancement in the liver.

Preparation and Evaluation of Probucol-Phospholipid Complex with Enhanced Bioavailability and No Food Effect.

To enhance the oral bioavailability and eliminate the food effect of probucol. Probucol-phospholipid complex was prepared using solvent-evaporation method in this research. Several methods were used to validate the formation of complexes, such as FT-IR, SEM, DSC and PXRD, and the solubility of PRO and PRO-PLC was detected by HPLC. Pharmacokinetic testing was conducted in the fasted and fed state. FTIR, SEM, DSC and PXRD validated the existence of PRO-PLC. The solubility of PRO in complexes was 15.05 µg/mL, which was 215-fold of the PRO-API. The dissolution rate was increased by preparing PRO-PLC. Compared with commercial tablets, the PRO-PLC complexes exhibited higher peak plasma concentration (1.69 ± 0.44 µg/mL), increased AUC0-24 h (6.8 ± 1.3 µg/mL h), which mean the bioavailability of PRO was increased. In addition, the absorption of PRO was not interfered with food. In conclusion, an improved solubility and bioavailability was achieved with the preparation of PRO-PLC. Additionally, the dissolution behaviour was good and the food effect was eliminated.

Chitosan coated chlorogenic acid and rutincomposite phospholipid liposomes: Preparation, characterizations, permeability and pharmacokinetic.

In order to research and enhance bioavailability of chlorogenic acid and rutin(CA-R) via the oral route, chitosan coated composite phospholipid liposomes (C-CPLs) were applied to study on preparation, permeability and pharmacokinetic of C-CA-R-CPLs. TheC-CA-R-CPLs were prepared by the method of ethanol injection. The entrapment efficiency (EE), average particle sizes, polymer disperse index (PDI), zeta potential, shape and in vitro drug release were investigated to characterize physicochemical parameters of C-CA-R-CPLs. The penetration properties from C-CA-R-CPLs were studied through Caco-2 cells model and the pharmacokinetics in Sprague-Dawley (SD) rats were evaluated by rat jugular vein intubation tube. The EE of C-CA-R-CPLs of CA and R was 91.3±2.13% and 92.6±2.44%, particle size of C-CA-R-CPLs was 176.7±2.3 nm, PDI was 0.207±0.014 and zeta potential of 12.61±1.33 mV. CA-R-CPLs and C-CA-R-CPLs were spherical or elliptical sphere and the bilayer of the CPL was observed obviously under transmission electron. The Cmax, t1/2 and AUC0-12 h values of CA and R for groups of C-CA-R-CPLs were significantly increased.In conclusion, TheC-CA-R-CPLs as a novel nano-formulation have potential to be used to enhance the oral bioavailability of poorlywater-soluble drugs after oral administration.

Dual 7-ethyl-10-hydroxycamptothecin conjugated phospholipid prodrug assembled liposomes with in vitro anticancer effects.

7-Ethyl-10-hydroxycamptothecin (SN38), as a highly active topoisomerase I inhibitor, is 200-2000-fold more cytotoxic than irinotecan (CPT-11) commercially available as Camptosar®. However, poor solubility and low stability extensively restricted its clinical utility. In this report, dual SN38 phospholipid conjugate (Di-SN38-PC) prodrug based liposomes were developed in order to compact these drawbacks. Di-SN38-PC prodrug was first synthesized by inhomogeneous conjugation of two SN38-20-O-succinic acid molecules with L-α-glycerophosphorylcholine (GPC). The assembly of the prodrug was carried out without any excipient by using thin film method. Dynamic light scattering (DLS), transmission electron microscope (TEM) and cryogenic transmission electron microscopy (cyro-TEM) characterization indicated that Di-SN38-PC can form spherical liposomes with narrow particle size (<200nm) and negatively charged surface (-21.6±3.5mV). The loading efficiency of SN38 is 65.2 wt.% after a simple calculation. In vitro release test was further performed in detail. The results demonstrated that Di-SN38-PC liposomes were stable in neutral environment but degraded in a weakly acidic condition thereby released parent drug SN38 effectively. Cellular uptake studies reflected that the liposomes could be internalized into cells more significantly than SN38. In vitro antitumor activities were finally evaluated by MTT assay, colony formation assay, flow cytometry, RT-PCR analysis and Western Blot. The results showed that Di-SN38-PC liposomes had a comparable cytotoxicity with SN38 against MCF-7 and HBL-100, and a selective promotion of apoptosis of tumor cells. Furthermore, a pharmacokinetics test showed that Di-SN38-PC liposomes had a longer circulating time in blood compared with the parent drug. All the results indicate that Di-SN38-PC liposomes are an effective delivery system of SN38.

In Vitro-In Vivo Evaluation of Novel Co-spray Dried Rifampicin Phospholipid Lipospheres for Oral Delivery.

The objective of this study comprises of developing novel co-spray dried rifampicin phospholipid lipospheres (SDRPL) to investigate its influence on rifampicin solubility and oral bioavailability. Solid-state techniques were employed to characterize the liposphere formulation. SDRPL solubility was determined in distilled water. BACTEC 460TB System was employed to evaluate SDRPL antimycobacterial activity. The oral bioavailability of the lipospheres was evaluated in Sprague Dawley rats. Lipospheres exhibited amorphous, smooth spherical morphology with a significant increase (p < 0.001) in solubility of SDRPL (2:1), 350.9 ± 23 versus 105.1 ± 12 µg/ml and SDRPL (1:1) 306.4 ± 20 versus 105.1 ± 12 µg/ml in comparison to rifampicin (RMP). SDRPL exhibited enhanced activity against Mycobacterium tuberculosis, H37Rv strain, with over twofolds less minimum inhibitory concentration (MIC) than the free drug. Lipospheres exhibited higher peak plasma concentration (109.92 ± 25 versus 54.31 ± 18 µg/ml), faster T max (two versus four hours), and enhanced area under the curve (AUC0-∞) (406.92 ± 18 versus 147.72 ± 15 µg h/L) in comparison to pure RMP. Thus, SDRPL represents a promising carrier system exhibiting enhanced antimycobacterial activity and oral bioavailability of rifampicin.

Biocompatible Phospholipid-Based Mixed Micelles for Tamoxifen Delivery: Promising Evidences from In - Vitro Anticancer Activity and Dermatokinetic Studies.

Tamoxifen (TAM) is frequently prescribed for the management breast cancer, but is associated with the challenges like compromised aqueous solubility and poor bioavailability to the target site. It was envisioned to develop phospholipid-based mixed micelles to explore the promises offered by the biocompatible carriers. Various compositions were prepared, employing soya lecithin, polysorbate 80, sodium chloride/dextrose, and water, by self-assembled technique. The formulations were characterized for micromeritics and evaluated for in vitro drug release, hemolysis study, dermatokinetic studies on rodents, and cytotoxicity on MCF-7 cell lines. Cellular uptake of the system was also studied using confocal laser scanning microscopy. The selected composition was of sub-micron range (28.81 ± 2.1 nm), with spherical morphology. During in-vitro studies, the mixed micelles offered controlled drug release than that of conventional gel. Cytotoxicity was significantly enhanced and IC50 value was reduced that of the naïve drug. The bioavailability in epidermis and dermis skin layers was enhanced approx. fivefold and threefold, respectively. The developed nanosystem not only enhanced the efficacy of the drug but also maintained the integrity of skin, as revealed by histological studies. The developed TAM-nanocarrier possesses potential promises for safe and better delivery of TAM.

The Effect of Lipid Emulsion on Pharmacokinetics of Bupivacaine in Rats: Long-Chain Triglyceride Versus Long- and Medium-Chain Triglyceride.

BACKGROUND: Lipid infusions have been proposed to treat local anesthetic-induced cardiac toxicity. This study compared the effects of long-chain triglyceride (LCT) emulsions with those of long- and medium-chain triglyceride (LCT/MCT) emulsions on the pharmacokinetics of bupivacaine in a rat model. METHODS: After administration of intravenous infusion of bupivacaine at 2 mg·kg·min for 5 minutes in Sprague-Dawley (SD) rats, either Intralipid 20%, an LCT emulsion (LCT group, n = 6), or Lipovenoes 20%, an LCT/MCT emulsion (LCT/MCT group, n = 6), was infused at 2mg·kg·min for 5 minutes. The concentrations of total plasma bupivacaine and bupivacaine that were not bound by lipid (lipid unbound) were measured by a liquid chromatography-tandem mass spectrometric method. A 2-compartmental analysis was performed to calculate the lipid-bound percentage of bupivacaine and its pharmacokinetics. RESULTS: In the LCT group, the clearance (15 ± 2 vs 10 ± 1 mL·min·kg, P = .003) was higher; the volume of distribution (0.57 ± 0.10 vs 0.36 ± 0.11 L·kg, P = .007) and K21 (0.0100 ± 0.0018 vs 0.0070 ± 0.0020 min, P = .021, P' = .032) were larger; and the area under the blood concentration-time curve 0 - t; (605 ± 82 vs 867 ± 110 mgL·min, P =.001) and the area under the blood concentration-time curve (0 - ∞) (697 ± 111 vs 991 ± 121 mgL·min, P =.001) were less, when compared with the LCT/MCT group. CONCLUSIONS: LCT emulsions are more effective than LCT/MCT emulsions in the metabolism of bupivacaine through demonstration of a superior pharmacokinetic profile.

Reliability, repeatability, and reproducibility of pulmonary transit time assessment by contrast enhanced echocardiography.

BACKGROUND: The aim of this study is to investigate the inter and intra-rater reliability, repeatability, and reproducibility of pulmonary transit time (PTT) measurement in patients using contrast enhanced ultrasound (CEUS), as an indirect measure of preload and left ventricular function. METHODS: Mean transit times (MTT) were measured by drawing a region of interest (ROI) in right and left cardiac ventricle in the CEUS loops. Acoustic intensity dilution curves were obtained from the ROIs. MTTs were calculated by applying model-based fitting on the dilution curves. PTT was calculated as the difference of the MTTs. Eight raters with different levels of experience measured the PTT (time moment 1) and repeated the measurement within a week (time moment 2). Reliability and agreement were assessed using intra-class correlations (ICC) and Bland-Altman analysis. Repeatability was tested by estimating the variance of means (ANOVA) of three injections in each patient at different doses. Reproducibility was tested by the ICC of the two time moments. RESULTS: Fifteen patients with heart failure were included. The mean PTT was 11.8 ± 3.1 s at time moment 1 and 11.7 ± 2.9 s at time moment 2. The inter-rater reliability for PTT was excellent (ICC = 0.94). The intra-rater reliability per rater was between 0.81-0.99. Bland-Altman analysis revealed a bias of 0.10 s within the rater groups. Reproducibility for PTT showed an ICC = 0.94 between the two time moments. ANOVA showed no significant difference between the means of the three different doses F = 0.048 (P = 0.95). The mean and standard deviation for PTT estimates at three different doses was 11.6 ± 3.3 s. CONCLUSIONS: PTT estimation using CEUS shows a high inter- and intra-rater reliability, repeatability at three different doses, and reproducibility by ROI drawing. This makes the minimally invasive PTT measurement using contrast echocardiography ready for clinical evaluation in patients with heart failure and for preload estimation.

Straight Vessel Pattern and Rapid Filling Time: Characteristic Findings on Contrast-Enhanced Sonography of Testicular Lymphoma.

Six patients with 7 lesions that were histologically confirmed as primary testicular lymphoma were preoperatively investigated with a standardized sonographic protocol including contrast-enhanced sonography. Duplex and contrast-enhanced sonography showed marked hypervascularization in all 7 lesions. On contrast-enhanced sonography, the filling time of lymphomatous lesions was significantly shorter than the filling time of a size-matched sample of 10 patients with seminomas (P < .0001). The sonographic hallmarks of testicular lymphoma in our case series were as follows: (1) sharply demarcated homogeneous hypoechoic testicular lesions with marked hypervascularization; (2) a rapid (<7 seconds) filling time of contrast bubbles; and (3) a straight and parallel course of intralesional vessels on contrast-enhanced sonography.

A randomised trial comparing the efficacy and safety of topical ketoprofen in Transfersome(®) gel (IDEA-033) with oral ketoprofen and drug-free ultra-deformable Sequessome™ vesicles (TDT 064) for the treatment of muscle soreness following exercise.

We compared the effectiveness of topical ketoprofen in Transfersome(®) gel (IDEA-033) with oral ketoprofen and drug-free Sequessome™ vesicles (FLEXISEQ(®) Sport; TDT 064) in reducing calf muscle soreness. One hundred and sixty eight healthy individuals with a pain score ≥ 3 (10-point scale) 12-16 h post-exercise (walking down stairs with an altitude of 300-400 m) were randomised to receive IDEA-033 plus oral placebo (two dose groups), oral ketoprofen plus TDT 064, or TDT 064 plus oral placebo. The primary endpoint was muscle soreness reduction from pre-dosing to Day 7. Higher pain scores were recorded with oral ketoprofen plus TDT 064 (mean ± s 462.4 ± 160.4) versus IDEA-033 plus oral placebo (434.7 ± 190.8; P = 0.2931) or TDT 064 plus oral placebo (376.2 ± 159.1; P = 0.0240) in the 7 days post-exercise. Recovery from muscle soreness was longer with oral ketoprofen plus TDT 064 (mean 91.0 ± 19.5 h) versus IDEA-033 plus placebo (mean 81.4 ± 22.9 h; P = 0.5964) or TDT 064 plus placebo (mean 78.9 ± 22.8 h; P = 0.0262). In conclusion, ultradeformable phospholipid vesicles ± ketoprofen did not retard recovery from muscle soreness. TDT 064 improves osteoarthritis-related pain and could be of interest as a treatment for joint pain during and post-exercise.

Encapsulation of low lipophilic and slightly water-soluble dihydroartemisinin in PLGA nanoparticles with phospholipid to enhance encapsulation efficiency and in vitro bioactivity.

CONTEXT: PLGA nanoparticles have been widely utilised to encapsulate lipophilic drugs for sustained release. OBJECTIVE: This study was to enhance encapsulation efficiency and drug loading for the poorly lipophilic drug dihydroartemisinin (DHA) in PLGA nanoparticles, where amphiphilic phospholipid was employed as the intermediate. MATERIALS AND METHODS: DHA-phospholipid complex formulation was optimised using the response surface method. DHA-phospholipid complex-nanoparticles (DHA-PLC-NPs) were prepared using the solvent evaporation method. RESULTS: The particle size, zeta potential, entrapment efficiency and drug loading of the nanoparticles were 265.3 ± 7.9 nm, -21.4 ± 6.3 mV, 74.2 ± 6.5% and 2.80 ± 0.35%, respectively. Compared with the rapidly released free form, DHA underwent sustained release from the nanoparticles. DHA-PLC-NPs presented stronger cell proliferative inhibition than DHA treatment alone and apoptosis was obviously induced after DHA-PLC-NPs treatment. CONCLUSION: Phospholipid complexes are useful intermediate to improve the lipophilicity of drugs, the interaction with the hydrophobic core of PLGA and the encapsulation efficiency of poorly lipophilic drugs in polymeric nanoparticles.

Development and Evaluation of a Novel Delivery System Containing Phytophospholipid Complex for Skin Aging.

Citrus auranticum and Glycyrrhiza glabra are rich in anti-oxidant polyphenols helpful in prevention of skin aging. Polyphenols have high polarity and lower skin penetration resulting in lower cutaneous delivery. The present work is attempted to develop a novel polyherbal phospholipid complex cream to improve cutaneous delivery of polyphenols for sustained anti-oxidant action. Phytochemical and in vitro anti-oxidant evaluation was done on methanolic extracts of orange peel and liquorice powder. Total phenolic content, total flavonoid content, and anti-oxidant assays were done on different ratios of orange peel and liquorice extract. Ratio 1:2 gave highest total phenolic content (TPC) (530.00 ± 1.56 mg gallic acid equivalent (GAE) g(-1) extract), total flavonoid content (TFC) (246.25 ± 1.03 mg rutin equivalent (RUE) g(-1) extract), 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity (87.99 ± 0.64%), and H2O2 scavenging activity (72.47 ± 0.86%) and hence was used for formulation. Solvent evaporation method using methanol with 1:1 extract to phospholipid ratio was found to have entrapment efficiency of 93.22 ± 0.26%. Evaluation parameters like scanning electron microscopy (SEM), Fourier transform infrared spectrophotometry (FT-IR), and differential scanning calorimetry (DSC) confirmed formation of complex. The complex was formulated as oil-in-water cream and evaluated for various parameters. The optimized cream containing 1% complex was non-irritant and was found to be stable for 3-month period under conditions of stability study. Ex vivo diffusion studies showed that extract phospholipid complex cream had better retention of polyphenols in the skin when compared to conventional extract cream giving prolonged and stronger topical action. The cream had an anti-elastase activity of 28.02 ± 0.95% at concentration of 3000 µg ml(-1) (w/v). Thus, the developed safe and stable polyherbal phytophospholipid complex cream exhibited good potential as anti-aging cosmeceutical.

[Pharmacokinetics Study on Curcumin Hydroxypropyl-ß-Cyclodextrin Phospholipid Complex in Rats].

OBJECTIVE: To compare the in vivo pharmacokinetics of curcumin hydroxypropyl-ß-cyclodextrin phospholipid complex, curcumin hydroxypropyl-ß-cyclodextrin and curcumin phospholipid complex, and to discuss the advantage of hydroxypropyl-ß-cyclodextrin phospholipid complex as carrier. METHODS: Drawing blood after SD rats were oral administered with the above preparations and free drug at 50 mg/kg( corresponding to curcumin) , and the blood concentration were determined by HPLC. RESULTS: The AUC0-∞ of curcumin hydroxypropyl-ß-cyclodextrin phospholipid complex was(1 126. 20 ± 323. 24) g/(L . h), which was 5. 89, 1. 49 and 1. 17 times as curcumin (191. 08 ± 43. 27) µg/( L . h), curcumin phospholipid complex(754. 93 ± 55. 33) µg/(L . h), curcumin hydroxypropyl-ß- cyclodextrin(961. 21 ± 253. 65) µg/(L . h). CONCLUSION: The curcumin hydroxypropyl-ß-cyclodextrin phospholipid complex has a better absorption property than curcumin phospholipid complex and curcumin hydroxypropyl-ß-cyclodextrin, which is more beneficial to improve the bioavailability.

Decreased reticuloendothelial system clearance and increased blood half-life and immune cell labeling for nano- and micron-sized superparamagnetic iron-oxide particles upon pre-treatment with Intralipid.

BACKGROUND: Superparamagnetic iron-oxide nanoparticles are useful as contrast agents for anatomical, functional and cellular MRI, drug delivery agents, and diagnostic biosensors. Nanoparticles are generally cleared by the reticuloendothelial system (RES), in particular taken up by Kupffer cells in the liver, limiting particle bioavailability and in-vivo applications. Strategies that decrease the RES clearance and prolong the circulation residence time of particles can improve the in-vivo targeting efficiency. METHODS: Intralipid 20.0%, an FDA approved nutritional supplement, was intravenously administered in rats at the clinical dose (2g/kg) 1h before intravenous injection of ultra-small superparamagnetic iron-oxide (USPIO) or micron-sized paramagnetic iron-oxide (MPIO) particles. Blood half-life, monocyte labeling efficiency, and particle biodistribution were assessed by magnetic resonance relaxometry, flow cytometry, inductively-coupled plasma MS, and histology. RESULTS: Pre-treatment with Intralipid resulted in a 3.1-fold increase in USPIO blood half-life and a 2-fold increase in USPIO-labeled monocytes. A 2.5-fold increase in MPIO blood half-life and a 5-fold increase in MPIO-labeled monocytes were observed following Intralipid pre-treatment, with a 3.2-fold increase in mean iron content up to 2.60pg Fe/monocyte. With Intralipid, there was a 49.2% and 45.1% reduction in liver uptake vs. untreated controls at 48h for USPIO and MPIO, respectively. CONCLUSIONS: Intralipid pre-treatment significantly decreases initial RES uptake and increases in-vivo circulation and blood monocyte labeling efficiency for nano- and micron-sized superparamagnetic iron-oxide particles. GENERAL SIGNIFICANCE: Our findings can have broad applications for imaging and drug delivery applications, increasing the bioavailability of nano- and micron-sized particles for target sites other than the liver.