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.

Use of combined nanocarrier system based on chitosan nanoparticles and phospholipids complex for improved delivery of ferulic acid.

A novel nanocarrier system of phospholipids complex loaded chitosan nanoparticles (FAPLC CNPs) was developed to improve the oral bioavailability and antioxidant potential of FA. FAPLC CNPs were optimized using a Box-Behnken Design (BBD). FAPLC CNPs were characterized using differential scanning calorimetry, Fourier transforms infrared spectroscopy, powder x-ray diffractometry, proton nuclear magnetic resonance, solubility, in vitro dissolution, ex vivo permeation, and in vivo antioxidant activity in carbon tetrachloride (CCl4)-induced albino rat model. The characterization studies indicated a formation of the complex as well as FAPLC CNPs. The FAPLC CNPs exhibited a lower particle size ~123.27 nm, PDI value ~0.31, and positive zeta potential ~32 mV respectively. Functional characterization studies revealed a significant improvement in the aqueous solubility, dissolution, and permeation rate of FAPLC and FAPLC CNPs compared to FA and FA CNPs. The FAPLC CNPs showed significant enhancement of in vivo antioxidant activity of FA by restoring the elevated marker enzymes in the CCl4-intoxicated rat model compared to FA CNPs. Moreover, the pharmacokinetic analysis demonstrated a significant enhancement of oral bioavailability of FA from FAPLC CNPs compared to FA CNPs. These findings show that FAPLC CNPs could be used as an effective nanocarrier for improving the oral delivery of FA.

Development of liquiritigenin-phospholipid complex with the enhanced oral bioavailability.

In the present study, liquiritigenin-phospholipid complex (LPC) was developed and evaluated to increase the oral bioavailability of liquiritigenin. A single-factor test methodology was applied to optimize the formulation and process for preparing LPC. The effects of solvent, drug concentration, reaction time, temperature and drug-to-phospholipid ratio on encapsulation efficiency were investigated. LPCs were characterized by UV-visible spectroscopy, differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and powder X-ray diffractometry (PXRD). The apparent solubility and n-octanol/water partition coefficient were tested. The pharmacokinetic characteristics and bioavailability of the LPC were investigated after oral administration in rats in comparison with liquiritigenin alone. An LPC was successfully prepared. The optimum level of various parameters for liquiritigenin-phospholipid complex was obtained at the drug concentration of 8 mg·mL-1, reaction time for 15 min, reaction temperature of 30 ℃, a ratio of 1∶4.5 (W/W) drug-to-phospholipid and anhydrous ethanol as reaction solvent. Compared to liquiritigenin, the AUC0-t of the LPC was increased by 239%. The liquiritigenin-phospholipid complex significantly increase the lipid solubility and bioavailability of liquiritigenin, suggesting that it is an effective formulation for further development and clinical applications.

One-Step Microfluidic Coating of Phospholipid Microbubbles with Natural Alginate Polymer as a Delivery System for Human Epithelial Lung Adenocarcinoma.

In this study, the neoplastic drug frequently used in the treatment of lung cancer, carboplatin is loaded to microbubbles via a microfluidic platform. In order to increase the drug loading capacity of microbubbles, carboplatin is encapsulated into alginate polymer layer. The phospholipid microbubbles (MBs) are synthesized by MicroSphere Creator, which is connected with T-junction and micromixer for the treatment with CaCl2 solution to provide gelation of the alginate coated phospholipid microbubbles (AMBs). The carboplatin loaded alginate coated phospholipid microbubbles (CAMBs) result in 12.2 ± 0.21 µm mean size, obtained by mixing with 0.05% CaCl2 using T-junction. The cytotoxic activities of the synthesized MBs, AMBs, and CAMBs are also investigated with the 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) (MTT) and live/dead fluorescent dying assays in the A549 and BEAS-2B cell lines. The one-step microfluidic coating of lipid microbubbles with natural alginate polymer appears to be a promising strategy for enhanced drug reservoir properties.

Fabrication and assessment of milk phospholipid-complexed antioxidant phytosomes with vitamin C and E: A comparison with liposomes.

Evidences have shown that phytosome assemblies are novel drug delivery system. However, studies of phytosomes in food applications are scarce. The characteristics of milk phospholipid assemblies and their functionality in terms of in vitro digestibility and bioavailability of encapsulated nutrients (ascorbic acid and α-tocopherol) were studied. The phytosomes were fabricated using ethanolic evaporation technique. Spectral analysis revealed that polar parts of phospholipids formed hydrogen bonds with ascorbic acid hydroxyl groups, further, incorporating ascorbic acid or α-tocopherol into the phospholipid assembly changed the chemical conformation of the complexes. Phospholipid-ascorbic acid phytosomes yielded an optimal complexing index of 98.52 ± 0.03% at a molar ratio of 1:1. Phytosomes exhibited good biocompatibility on intestinal epithelial cells. The cellular uptake of ascorbic acid was 29.06 ± 1.18% for phytosomes. It was higher than that for liposomes (24.14 ± 0.60%) and for ascorbic acid aqueous solution (1.17 ± 0.70%).

Phospholipid Oxygen Microbubbles for Image-Guided Therapy.

In recent work, oxygen microbubbles (OMB) have been shown to oxygenate hypoxic tumors, increase radio-sensitivity and improve tumor control by radiation therapy. Compared to intra-tumoral injection, intravenous delivery of adjuvant agents such as OMBs for radiotherapy offers an attractive means of achieving true theranostic function in a minimally invasive manner via contrast-enhanced ultrasound (CEUS), while reducing the risk of injury, infection or displacing tumor cells. However, short intravascular circulation times with conventional DSPC-lipid OMBs may lead to premature off-target dissolution of OMBs with an associated reduction in tumoral oxygen delivery. Prior work on microbubble stability and gas exchange suggests that increasing phospholipid acyl-chain length of the encapsulating shell and OMB size may increase circulation persistence, delivery and dissolved oxygen content. In the following studies, we investigate the effect of two phospholipid shell compositions, DSPC (C18:0) and DBPC (C22:0), as well as three size distributions (0.5-2 µm, 2-10 µm and polydisperse) on OMB circulation persistence utilizing CEUS in the kidneys of live C57B1/6 male and female mice, six weeks of age. DBPC OMB formulations demonstrated increased circulation half-lives versus DSPC formulations (2.4 ± 1.0 vs. 0.6 ± 0.5 s, p<0.01 for 2-10 µm), as well as an increased maximum intensity by over tenfold (p<0.01). Size-dependent effects remained consistent across both formulations with larger 2-10 µm microbubbles demonstrating significantly increased half-lives (2.4 ± 1.0 vs. 0.3 ± 0.2 s, p < 0.01) compared to smaller 0.5-2 µm formulations of DBPC. These studies indicate that DBPC 2-10 µm OMBs may be improved adjuvant agents for radiotherapy with significant potential for CEUS interrogation.

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency.

BACKGROUND: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. OBJECTIVE: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. METHODS: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). RESULTS: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. CONCLUSION: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

Intestinal bioavailability of n-3 long-chain polyunsaturated fatty acids influenced by the supramolecular form of phospholipids.

The aim of this work was to study the bioavailability of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA), i.e. eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), carried by marine phospholipids (PL) and formulated in different supramolecular forms. Marine PL were administrated in rats either (1) in bulk form, or (2) as an oil-in-water emulsion, or (3) as liposomes. Each dietary formulation was characterized by a similar fatty acid (FA) profile and provided the same n-3 LC-PUFA amount. Intestinal bioavailability of n-3 LC-PUFA was monitored in the lymph compartment in a duct fistula model. On the one hand, the emulsification of plant oils with PL increased the overall intestinal absorption of dietary FA by 84% without affecting the lymph FA profile compared with the bulk form, suggesting that emulsification favoured the absorption of the total dietary FA derived from both triglycerides (TG) and PL. On the other hand, the liposome form did not modify the lymph lipid amount compared with the bulk form, but specifically increased the n-3 LC-PUFA levels. The dietary forms of PL influenced the position of some FA on the glycerol backbone of lymph TG and PL. In conclusion, using marine PL as an emulsifier promoted total FA absorption independently of the dietary lipid carrier (TG or PL) and the FA type. Structuring PL as liposomes specifically increased the intestinal bioavailability of FA esterifed in this lipid class, such as DHA, resulting in a higher incorporation into lymph lipids. Thus, using specific PL supramolecular forms would guide n-3 LC-PUFA towards total lipid absorption or specific FA absorption, according to the dietary needs.

Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs.

Background: The poor biopharmaceutical properties of thymoquinone (TQ) obstruct its development as a hepatoprotective agent. To surmount the delivery challenges of TQ, phospholipid nanoconstructs (PNCs) were constructed.Method: PNCs were constructed employing microemulsification technique and systematic optimization by three-factor three level Box-Behnken design.Result: Optimized PNC composition exhibited nano size (<100 nm), spherical morphology, within acceptable range of polydispersity index (0.55), high drug entrapment efficiency (>90%), controlled drug release pattern, and neutral surface charge (zeta potential of -0.65 mV). After oral administration of a single dose of PNC, it showed a relative bioavailability of 386.03% vis-à-vis plain TQ suspension. Further, TQ-loaded PNC demonstrated significant enhanced hepato-protective effect vis-à-vis pure TQ suspension and silymarin, as evidenced by reduction in the ALP, ALT, AST, bilirubin, and albumin level and ratified by histopathological analysis.Conclusion: TQ-loaded PNCs can be efficient nano-platforms for the management of hepatic disorders and promising drug delivery systems to enhance oral bioavailability of this hydrophobic molecule.

Time-of-flight resolved light field fluctuations reveal deep human tissue physiology.

Red blood cells (RBCs) transport oxygen to tissues and remove carbon dioxide. Diffuse optical flowmetry (DOF) assesses deep tissue RBC dynamics by measuring coherent fluctuations of multiply scattered near-infrared light intensity. While classical DOF measurements empirically correlate with blood flow, they remain far-removed from light scattering physics and difficult to interpret in layered media. To advance DOF measurements closer to the physics, here we introduce an interferometric technique, surmounting challenges of bulk motion to apply it in awake humans. We reveal two measurement dimensions: optical phase, and time-of-flight (TOF), the latter with 22 picosecond resolution. With this multidimensional data, we directly confirm the unordered, or Brownian, nature of optically probed RBC dynamics typically assumed in classical DOF. We illustrate how incorrect absorption assumptions, anisotropic RBC scattering, and layered tissues may confound classical DOF. By comparison, our direct method enables accurate and comprehensive assessment of blood flow dynamics in humans.

Phospholipid prodrug conjugates of insoluble chemotherapeutic agents for ultrasound targeted drug delivery.

The hydrophobicity and high potency of many therapeutic agents makes them difficult to use effectively in clinical practice. This work focuses on conjugating phospholipid tails (2T) onto podophyllotoxin (P) and its analogue (N) using a linker and characterizing the effects of their incorporation into lipid-based drug delivery vehicles for triggered ultrasound delivery. Differential Scanning Calorimetry results show that successfully synthesized lipophilic prodrugs, 2T-P (~28 % yield) and 2T-N(~26 % yield), incorporate within the lipid membranes of liposomes. As a result of this, increased stability and incorporation are observed in 2T-P and 2T-N in comparison to the parent compounds P and N. Molecular dynamic simulation results support that prodrugs remain within the lipid membrane over a relevant range of concentrations. 2T-N's (IC50: 20 nM) biological activity was retained in HeLa cells (cervical cancer), whereas 2T-P's (IC50: ~4 µM) suffered, presumably due to steric hindrance. Proof-of-concept studies using ultrasound in vitro microbubble and nanodroplet delivery vehicles establish that these prodrugs are capable of localized drug delivery. This study provides useful information about the synthesis of double tail analogues of insoluble chemotherapeutic agents to facilitate incorporation into drug delivery vehicles. The phospholipid attachment strategy presented here could be applied to other well suited drugs such as gemcitabine, commonly known for its treatment of pancreatic cancer.

Empirical and Theoretical Characterization of the Diffusion Process of Different Gadolinium-Based Nanoparticles within the Brain Tissue after Ultrasound-Induced Permeabilization of the Blood-Brain Barrier.

Low-intensity focused ultrasound (FUS), combined with microbubbles, is able to locally, and noninvasively, open the blood-brain barrier (BBB), allowing nanoparticles to enter the brain. We present here a study on the diffusion process of gadolinium-based MRI contrast agents within the brain extracellular space after ultrasound-induced BBB permeabilization. Three compounds were tested (MultiHance, Gadovist, and Dotarem). We characterized their diffusion through in vivo experimental tests supported by theoretical models. Specifically, by estimation of the free diffusion coefficients from in vitro studies and of apparent diffusion coefficients from in vivo experiments, we have assessed tortuosity in the right striatum of 9 Sprague Dawley rats through a model correctly describing both vascular permeability as a function of time and diffusion processes occurring in the brain tissue. This model takes into account acoustic pressure, particle size, blood pharmacokinetics, and diffusion rates. Our model is able to fully predict the result of a FUS-induced BBB opening experiment at long space and time scales. Recovered values of tortuosity are in agreement with the literature and demonstrate that our improved model allows us to assess that the chosen permeabilization protocol preserves the integrity of the brain tissue.

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.

Evaluation of OM3-PL/FFA Pharmacokinetics After Single and Multiple Oral Doses in Healthy Volunteers.

PURPOSE: The US Food and Drug Administration has approved several omega-3 (OM3)-containing prescription drugs for the treatment of severe hypertriglyceridemia (HTG). However, there is still a need to develop formulations with high bioavailability irrespective of the fat content and time of the meal. OM3-phospholipid (PL)/free fatty acid (FFA) is an investigational drug for the treatment of severe HTG containing naturally derived krill oil mixture of OM3, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as PL esters and as FFA. Both forms in OM3-PL/FFA are believed to be readily bioavailable. Per gram, OM3-PL/FFA contains a lower dose of EPA/DHA in comparison with already approved prescription drugs. The study aim was to evaluate OM3-PL/FFA pharmacokinetic (PK) properties after single and multiple oral doses of 1, 2, and 4 g in healthy subjects when receiving a Therapeutic Lifestyle Change (TLC) diet. The dose proportionality of the study drug, the effect of a high-fat (HF) meal on its PK properties and its safety profile after multiple administration were also explored. METHODS: In this Phase I, open-label, randomized, multiple-dose, single-center, parallel-design study, 42 healthy volunteers following a TLC diet were randomly assigned into 1 of 3 treatment groups in a 1:1:1 ratio to receive a single dose at day 1, followed by multiple oral doses of 1, 2, and 4 g/d for 14 days. At day 15, all subjects received a HF breakfast. FINDINGS: After once-daily dosing, based on graphic assessment, OM3-PL/FFA levels reached steady state within 7-10 days. Exposure of total EPA + DHA, total DHA, and total EPA (Cmax and AUC) appeared to be approximately proportional over the 1-4 g/d dose range. After 14 days of repeated daily dosing, accumulation was observed and was greater at the higher dose of the study product. When administered after a HF breakfast on day 15, median tmax, the geometric mean of AUC0-24 and Cmax were comparable with the values on day 14 across the 3 dose levels. IMPLICATIONS: OM3-PL/FFA was found to be well tolerated in healthy subjects. The study drug PK properties appeared to be approximately dose proportional over the 1-4 g/d dose range. The bioavailability of OM3-PL/FFA did not appear to be meaningfully affected by the fat content of the meal consumed before dose administration. This is clinically relevant because a low-fat diet is part of the management of patients with HTG.

Boronic-targeted albumin-shell oily-core nanocapsules for synergistic aromatase inhibitor/herbal breast cancer therapy.

Multi-modality strategies of albumin-mediated drug accumulation in tumor, boronate-based active tumor targeting and synergistic cancer therapy were combined together for effective treatment of breast cancer. Herein we report the development of albumin-shell oily-core nanocapsules (NCs), loaded with novel combination of hydrophobic drugs, exemestane (EXE) and hesperetin (HES), for targeted breast cancer therapy. This protein-lipid nanohybrid carrier was successfully fabricated using a simple protein-coating method based on the electrostatic adsorption of negatively charged albumin shell onto the oily core containing cationic surfactant. While EXE was directly encapsulated into the oily core, HES was pre-formulated in the form of phospholipid complex before solubilization in oily phase. In addition to albumin-mediated binding to albondin and SPARC, phenylboronic acid was chemically coupled to the albumin shell to confer additional tumor targeting. The targeted nanocarrier (TNC) demonstrated enhanced internalization into MCF-7 breast cancer cells resulting in synergistic cytotoxic activity with a combination index (CI) of 0.662 and dose reduction index (DRI) of 8.22 and 1.84 for EXE and HES, respectively. In vivo, TNC displayed superior anti-cancer activity in tumor-bearing mice compared to their non-targeted counterparts and the free drug combination. A significant reduction of both tumor volume (7-folds) and Ki67 expression (3-folds) was obtained by the targeted nanocarriers compared to positive control. Overall, the boronic-targeted albumin NCs offer a promising platform for hydrophobic drug combination against cancer therapy.

The effect of the saturation degree of phospholipid on the formation of a novel self-assembled nano-micellar complex carrier with enhanced intestinal permeability.

The aim of this research was to formulate a novel nano-micellar complex carrier with intrinsically enhanced intestinal permeability for rosuvastatin calcium (RSV); as a model of BCS class III active pharmaceutical ingredients (APIs). The model drug is used primarily for treating hypercholesterolemia. Three phospholipid types with different degrees of saturation were chosen for the study. The saturation degree of the phospholipids was calculated accurately by proton NMR. A D-optimal statistical design was utilized to correlate the saturation degree of the phospholipids with the physico-chemical characteristics of the prepared nano-micellar carrier. The nature of the interaction between the phospholipids and the model drug was studied by proton NMR, photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM). Molecular docking and molecular dynamics simulations were performed to understand the formation mechanism of the complex micelles on a molecular level. The results demonstrated that the interaction of the hydrophilic drug molecule with the polar head of a saturated phospholipid induces an intramolecular self-coiling of phospholipid saturated acyl chain leading to a structural transformation from a two-tailed cylindrical configuration into a one-tailed, surfactant-like configuration owing to the flexibility of the saturated chains. This transformation leads to the construction of a novel nano-micellar structure in which the drug has lower water solubility but higher lipophilicity than in traditional micelles. Permeability studies conducted on Caco-2 cells demonstrated that the novel nano-micellar carrier had superior permeability to that of the un-complexed hydrophilic drug. The optimized nano-micellar formulation showed significantly (P < 0.5) superior bioavailability in rats to that of the aqueous drug solution in terms of both the rate and extent of drug absorption. Overall, the results confirmed that the formation of the phospholipid nano-micellar complex increased the permeability of the hydrophilic BCS class III drug and converted it to a class BCS I drug by a simple and effective formulation technique.

The modulation of drug-loading stability within lipid membranes via medium chain triglycerides incorporation.

The current research aimed to explore medium chain triglycerides (MCT) incorporation in liposomes to overcome stability challenges when drugs with high molecular weight and payload are loaded within lipid membranes. A model drug clarithromycin was loaded in lipid dispersions with various MCT/phospholipids ratios (RM/P = 0, 0.5, 1.75 and 7.5 w/w). TEM images demonstrated a liposome-to-emulsion structural transformation by MCT incorporation to cause increased particle size (104.3-167.7 nm) but decreased zeta potential (-63.6 to -44.4 mV) of lipid particles. MCT incorporation produced biphasic release in PBS and accelerated released in plasma. The tolerance of liposomes for thermal sterilization, high temperature test and freeze-thaw cycles were significantly improved by MCT incorporation. However, MCT incorporation produced adverse effects on colloidal stability in plasma and pharmacokinetics behavior in vivo to some extent. MCT stabilizing mechanism attributes to the modulation of drug loading area and stability improvement of lipid carriers. MCT incorporated liposomes achieved 2-3 fold cellular uptake level than traditional liposomes without significant cytotoxicity. These results indicated that MCT incorporation could be a promising strategy to apply in liposome production to achieve stable drug loading.