Distearoylphosphatidylethanolamine-polyethylene Glycol Research Articles

Silk fibroin and hydroxypropyl cellulose composite injectable hydrogel-containing extracellular vesicles for myocardial infarction repair

Extracellular vesicles (EVs) have been recognized as one of the promising specific drugs for myocardial infarction (MI) prognosis. Nevertheless, low intramyocardial retention of EVs remains a major impediment to their clinical application. In this study, we developed a silk fibroin/hydroxypropyl cellulose (SF/HPC) composite hydrogel combined with AC16 cell-derived EVs targeted modification by folic acid for the treatment of acute myocardial infarction repair. EVs were functionalized by distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) via noncovalent interaction for targeting and accelerating myocardial infarction repair. In vitro, cytocompatibility analyses revealed that the as-prepared hydrogels had excellent cell viability by MTT assay and the functionalized EVs had higher cell migration by scratch assay. In vivo, the composite hydrogels can promote myocardial tissue repair effects by delaying the process of myocardial fibrosis and promoting angiogenesis of infarct area in MI rat model.

Self-Delivery Nanomedicines Reverse Thermal Resistance to Enhance Tumor Mild-Temperature Photothermal Therapy.

Tumoral thermal defense mechanisms considerably attenuate the therapeutic outcomes of mild-temperature photothermal therapy (PTT). Thus, developing a simple, efficient, and universal therapeutic strategy to sensitize mild-temperature PTT is desirable. Herein, we report self-delivery nanomedicines ACy NPs comprising a near-infrared (NIR) photothermal agent (Cypate), mitochondrial oxidative phosphorylation inhibitor (ATO), and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000), which have a high drug-loading efficiency that can reverse tumoral thermal resistance, thereby increasing mild-temperature PTT efficacy. ACy NPs achieved targeted tumor accumulation and performed NIR fluorescence imaging capability in vivo to guide tumor PTT for optimized therapeutic outcomes. The released ATO reduced intracellular ATP levels to downregulate multiple heat shock proteins (including HSP70 and HSP90) before PTT, which reversed the thermal resistance of tumor cells, contributing to the excellent results of mild-temperature PTT in vitro and in vivo. Therefore, this study provides a simple, biosafe, advanced, and universal heat shock protein-blocking strategy for tumor PTT.

A Stable Micellar Formulation of RAD001 for Intracerebroventricular Delivery and the Treatment of Alzheimer's Disease and Other Neurological Disorders.

A large body of evidence, replicated in many mouse models of Alzheimer's disease (AD), supports the therapeutic efficacy of the oral mammalian target of rapamycin inhibitors (mTOR-Is). Our preliminary data show that intracerebroventricular (ICV) administration of everolimus (RAD001) soon after clinical onset greatly diminished cognitive impairment and the intracellular beta amyloid and neurofibrillary tangle load. However, RAD001 shows >90% degradation after 7 days in solution at body temperature, thus hampering the development of proper therapeutic regimens for patients. To overcome such a drawback, we developed a stable, liquid formulation of mTOR-Is by loading RAD001 into distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000) micelles using the thin layer evaporation method. The formulation showed efficient encapsulation of RAD001 and a homogeneous colloidal size and stabilised RAD001, with over 95% of activity preserved after 14 days at 37 °C with a total decay only occurring after 98 days. RAD001-loaded DSPE-PEG2000 micelles were unchanged when stored at 4 and 25 °C over the time period investigated. The obtained formulation may represent a suitable platform for expedited clinical translation and effective therapeutic regimens in AD and other neurological diseases.

Understanding the rod-to-tube transformation of self-assembled ascorbyl dipalmitate lipid nanoparticles stabilized with PEGylated lipids.

We previously established a nanoparticle-based drug delivery system (DDS) for high-dose ascorbic acid therapy by self-assembly of a lipid-modified ascorbic acid derivative, L-ascorbyl 2,6-dipalmitate (ASC-DP). The particles' morphology should be modified for effective DDSs. Here, we modulated the morphology of self-assembled ASC-DP nanoparticles using two different PEGylated lipids, distearoylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) and cholesterol-polyethylene glycol (Chol-PEG), with various PEG molecular weights. At the preparation molar ratio of 10 : 1 (ASC-DP/PEGylated lipid), rod-like nanoparticles emerged in the ASC-DP/DSPE-PEG system, whereas the ASC-DP/Chol-PEG system yielded tube-like nanoparticles. The internal structures of both rod-like ASC-DP/DSPE-PEG and tube-like ASC-DP/Chol-PEG nanoparticles were similar to that of repeated ASC-DP bilayers. The particles' surfaces featured PEGylated lipids, which stabilized the structure and dispersion of the nanoparticles. For both systems, the particle size increased slightly with increasing the PEGylated lipid's PEG molecular weight. Increasing the PEG molecular weight decreased the inner tunnel size of tube-like ASC-DP/Chol-PEG nanoparticles. A mechanism has been proposed for the rod-to-tube transformation. Surface-layer free-energy changes owing to the mixing of multiple lipids and PEG chain repulsion are thought to underlie the inner tunnels' formation. The rod-to-tube morphology of self-assembled ASC-DP nanoparticles can be modulated by controlling the PEGylated lipids' structure, including the lipid species and the PEG chain length.

Modification of liposomes composed of a cationic lipid TMAG and an anionic lipid DSPG with a PEGylated lipid based on the investigation of lipid structures

Charged lipids are widely utilized in functional liposomes for controlled release and targeting of drugs. In this study, we prepared the liposomes composed of a cationic lipid N-(α-trimethylammonioacetyl)-distearoyl-D-glutamate chloride (TMAG) and an anionic lipid 1,2-dioctadecanoyl-sn-glycero-3-phospho-1′-rac-glycerol (DSPG) with the molar ratio of TMAG/DSPG = 0:10–10:0 by hydration and extrusion methods. SAXS study for the lipid thin films revealed the formation of lamellar structures of TMAG and DSPG. The lipid thin film, except for the composition of 5:5 and 6:4, formed a liposome with a size of ∼100 nm that could encapsulate riboflavin in the inner aqueous phase. The zeta potentials of liposomes with the composition of 0:10–4:6 showed negative charges, while those of 7:3–10:0 showed positive charges. As the composition approached from 0:10 or 10:0 to 5:5, the phase transition temperature of the lipid bilayer from liquid crystalline phase to gel phase became higher, and the extent of fluorescence anisotropy increased. Thus, the lipid bilayer around the equimolar mixture could form a rigid structure with low fluidity of lipid alkyl chains. The surface charge cancellation by the opposite ionic head groups and the less curvature of the rigid lipid bilayer should prevent the liposomal formation at the composition of 5:5 and 6:4. However, the equimolar composition of 5:5 could form a liposome by the modification of distearoylphosphatidylethanolamine-polyethyleneglycol 2000 (DSPE-PEG2000) into the lipid bilayer at the molar ratio of 4% because it can reduce the rigidity of the lipid bilayer, provide positive curvature to the lipid bilayer, and stabilize the liposome dispersion in water through steric hindrance.

Coumarin derivative dye sensitized NaYGdF4:Yb,Er nanoparticles with enhanced NIR II luminescence for bio-vascular imaging

Lanthanide-doped biocompatible nanoparticles have promising applications in near-infrared second region imaging due to their high chemical stability, enhanced photostability and sharp emission bandwidth. However, the weak light absorption capacity limits the application of rare-earth nanoparticles (RENPs) for bioimaging. We prepared a coumarin-derived dye sensitized NaYGdF4:Yb,Er nanoparticle probe, in which the organic dye enhances photon absorption through the sensitization process, improving the luminescence efficiency of the rare earth particles near 1000 and 1500 nm. In addition, good water solubility and stability of the probe are imparted by coating the particles with amphiphilic polymers distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) and polyacrylic acid. This composite probe with good biocompatibility and NIR II luminescence properties can be used for vascular imaging, providing a tool for the detection of hematologic-related diseases.

Preliminary Study on the Therapeutic Effect of Doxorubicin-Loaded Targeting Nanoparticles on Glioma.

Doxorubicin (DOX) is an anthracycline anticancer drug, which is often associated with drug resistance and cytotoxicity. More unfortunately, the biological barrier in the human environment can weaken the efficacy of DOX, such as the blood-brain barrier (BBB). This work attempts to make efforts to solve this problem. We used polyethylene glycol distearoylphosphatidylethanolamine (PEG-DSPE) as a nanocarrier and DOX as a model drug to construct a composite nanodrug (TF-PEG-DSPE/DOX NPs) by coupling transferrin (TF). The results of glioma experiments show that the nanodrug can effectively penetrate BBB to achieve an antitumor effect.

Microfluidic Preparation of Nanoparticles Using Poly(ethylene Glycol)-distearoylphosphatidylethanolamine for Solubilizing Poorly Soluble Drugs

Microfluidic systems have shown promise for the production of nanoparticles from mixtures of aqueous and organic solutions, including liposomes, oil-in-water nanoemulsions, and lipid nanoparticles. They offer important practical advantages, including low reagent consumption, parallelization, and automation, and are ideally suited to high-throughput optimization and scale-up. In this study, we developed a new method for the formulation of nanoparticles of poorly soluble drug compounds. The nanoparticles, prepared by microfluidic mixing using only poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE), were highly stable and uniform in size. By mixing an organic solution of poorly soluble cyclosporine A and PEG-DSPE with water in the microfluidic device, amorphous cyclosporine A nanoparticles (CsA-NPs), with an encapsulation efficiency of approximately 90% and a particle size of 100–200 nm, were obtained. Analysis of the microfluidic process parameters revealed that particle size distribution was significantly controlled by the flow rate ratio. The obtained CsA-NPs were stable for up to 150 days at room temperature, and the pharmacokinetic profile was similar to that of the commercial formulation containing Cremophor EL, which has been reported to induce serious adverse effects after intravenous administration. These findings provide a useful technical platform for the safe solubilization of poorly soluble compounds and their subsequent pharmaceutical development.

Long-circulating doxorubicin and schizandrin A liposome with drug-resistant liver cancer activity: preparation, characterization, and pharmacokinetic

The selectivity of chemotherapeutic agents for liver cancer is poor. When they kill tumour cells, they produce serious adverse reactions in the whole body and multidrug resistance (MDR) is also a major hurdle in liver cancer chemotherapy. Combination therapy is a useful method for overcoming MDR and reducing toxic and side effects. In this study, we developed a long-circulating codelivery system, in which doxorubicin (DOX) and schizandrin A (SchA) are combined against MCF-7/ADR cells. The DOX-SchA long-circulating liposome (DOX-SchA-Lip) was prepared using ammonium sulphate gradient method. The two drugs were co-encapsulated into the distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-mPEG2000) liposome and the liposome had an average particle size of (100 ± 3.5) nm and zeta electrical potential of (–31.3 ± 0.5) mV. The average encapsulation rate of DOX was 97.98% and that of SchA was 86.94%. DOX in liposome had good sustained-release effect. The results showed that DOX-SchA-Lip could significantly prolong the half-life (t 1/2z) of the DOX and SchA, increase their circulation time in vivo, improve its bioavailability and reduce their side effects. Liposome can effectively induce early apoptosis of HepG2/ADR cells and the cell cycle was blocked in S-phase by DOX-SchA-Lip in a dose-dependent manner. The IC50 of compound liposome to HepG2 and HepG2/ADR were 0.55 μmol/L and 1.38 μmol/L, respectively, which could significantly reverse the resistance of HepG2/ADR and the reversion multiple was 30.28. It was verified that DOX-SchA-Lip can effectively kill tumour cells and reverse MDR.

Surface PEGylated Cancer Cell Membrane-Coated Nanoparticles for Codelivery of Curcumin and Doxorubicin for the Treatment of Multidrug Resistant Esophageal Carcinoma

ObjectiveThe emergence of multi-drug resistance (MDR) in esophageal carcinoma has severely affected the effect of chemotherapy and shortened the survival of patients. To this end, we intend to develop a biomimetic nano-targeting drug modified by cancer cell membrane, and investigate its therapeutic effect.MethodsThe degradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with doxorubicin (DOX) and curcumin (Cur) were prepared by solvent evaporation method. TE10 cell membrane and Distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) were then coated on the PLGA NPs by membrane extrusion to prepare the PEG-TE10@PLGA@DOX-Cur NPs (PMPNs). Size and zeta potential of the PMPNs were analyzed by lazer particle analyzer, and the morphology of PMPNs was observed by transmission electron microscope. The TE10 cell membrane protein on PMPNs was analyzed by gel electrophoresis. The DOX-resistant esophageal cancer cell model TE10/DOX was established through high-dose induction. The In vitro homologous targeting ability of PMPNs was evaluated by cell uptake assay, and the in vitro anti-tumor effect of PMPNs was assessed through CCK-8, clone formation and flow cytometry. A Balb/c mouse model of TE10/DOX xenograft was constructed to evaluate the anti-tumor effect in vivo and the bio-safety of PMPNs.ResultsThe prepared cell membrane coated PMPNs had a regular spherical structure with an average diameter of 177 nm. PMPNs could directly target TE10 and TE10/DOX cells or TE10/DOX xenografted tumor and effectively inhibit the growth of DOX-resistant esophageal carcinoma. Besides, the PMPNs was confirmed to have high biosafety.ConclusionIn this study, a targeted biomimetic nano-drug delivery system PMPNs was successfully prepared, which overcome the MDR of esophageal carcinoma by co-delivering DOX and sensitizer curcumin.

The nanostructure of rod-like ascorbyl dipalmitate nanoparticles stabilized by a small amount of DSPE-PEG

Previously, we reported the formation of 100–200 nm disk- and tube-like nanoparticles by hydration of L-ascorbyl 2,6-dipalmitate (ASC-DP) and distearoylphosphatidylethanolamine polyethylene glycol 2000 (DSPE-PEG) films prepared at an initial molar ratio of 2:1. This study investigated the feasibility of nanoparticle formation with higher ASC-DP loading. Although particle size distribution determined by dynamic light scattering showed a multimodal pattern including micro-sized particles at a molar ratio of 3:1, the mean particle size gradually decreased with a further increased molar ratio. Homogeneous ca. 240 nm nanoparticles with a unimodal size distribution were obtained at a molar ratio of 10:1. FE-TEM showed that the nanoparticles at a molar ratio of 10:1 were rod-shaped with a diameter of ca. 100 nm and a length of ca. 300 nm. After centrifugation, X-ray analysis of the nanoparticle precipitates showed that these rod-like nanoparticles were composed of a series of lamellar structures with 3.7 nm repeated units. The molar ratio of ASC-DP/DSPE-PEG in the nanoparticle precipitates determined by 1H NMR measurements was 68.8:1. The rod-like nanoparticles should be composed of a core–shell structure, where a small amount of DSPE-PEG covers the lamellar structure of ASC-DP. Further increase in the ASC-DP/DSPE-PEG molar ratio over 33:1 no longer provided nanoparticles. Hence, to prepare a stable ASC-DP nanoparticle suspension, it is necessary to prepare ASC-DP/DSPE-PEG films containing at least 3 mol% DSPE-PEG.

Development and solidification of multifunction stabilizers formulated self-assembled core-shell Deacetyl mycoepoxydience nanosuspensions

In this study, a novel core-shell structure Deacetyl mycoepoxydience nanosuspensions (CS-DM-NSs) delivery system was successfully designed by self-assembly method and the solidification technology was also investigated. The Deacetyl mycoepoxydience (DM) nanocrystals core was prepared by anti-solvent precipitation with folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG2000-FA) and D-α-tocopheryl polyethylene glycol succinate (TPGS) as functional stabilizers. Then the DM nanocrystals core was completely wrapped by the polyethylene glycol-hyaluronic acid (PEG-HA) as shell. To improve the stability, the CS-DM-NSs were solidified by spray-drying and freeze-drying, respectively. The influence of the solidification approach on the solidified powders was demonstrated by TEM and SEM. Compared with the freeze dried CS-DM-NSs, the spray dried powder presented spherical in shape with smooth surface. The dissolution velocity of the two powders was higher than to the raw drug (3.5-fold and 4.5-fold, respectively). The solidified CS-DM-NSs presented dose- and time- dependent cytotoxicity to cancer cells (MCF-7) and significantly higher cytotoxicity than the free DM. In addition, there was no significant difference between the spray-drying and the freeze-drying solidified CS-DM-NSs. Overall, the CS-DM-NSs showed promising potential as a drug carrier for cancer therapy and the spray drying could be confidently used for the CS-DM-NSs solidification with higher stability, smaller particle size, and faster dissolution rate.

Targeted delivery of DOX by transferrin conjugated DSPE-PEG nanoparticles in leukemia therapy

In this study, transferrin (Tf) conjugated distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG) nanoparticles (DPT) was successfully prepared to deliver doxorubicin (DOX) to improve the chemotherapy efficacy of K562 leukemia cells. The results show that DPT were nanosized and presented spherical shaped particles, and the average particle size is about 80 nm. The DOX encapsulation efficiency of DPT was >70%. These nanoparticles could release DOX in the acid nucleus and facilitate the delivery of DOX after endocytosis. In addition, DPT is more targeted to K562 cancer cells than DSPE-PEG nanoparticles (DP). To be specific, the cytotoxic effect of DPT on cancer cells was significantly higher than that of DP, indicating that the tf modified nanoparticle system has better targeting efficiency. In summary, the results clearly show that the targeting of leukemia cells by the Tf -coupled nanoparticle system may pave the way for successful treatment of leukemia.

CRYPTOSOMES: A REVOLUTIONARY BREAKTHROUGH IN NOVEL DRUG DELIVERY

The vesicular drug delivery systems are promising approaches to overthrown the problems of drugs having lesser bioavailability and rapid elimination from the body. The four type of lipid based drug delivery systems are: solid-lipid particulate system, emulsion based system, solid lipid tablet and vesicular system. Cryptosomes, a novel emerging vesicular drug delivery system which can overcome the disadvantages associated with conventional drug delivery systems like high stability, increased bioavailability, sustained release, decreased elimination of rapidly metabolizable drugs etc. The word Cryptosome was orginated from Greek word ‘’Crypto’’ means hidden and ‘’Soma’’ means body. It is formed from the mixture of phospholipids like distearoyl phosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG) with distearoylphosphatidylcholine. These entire information regarding its origin and formation is explained in Dinesh Kumar et al. Vesicular systems symbolizes the use of vesicles in the different fields as carrier system or additives. This review disclose various vesicular drug delivery system and point out the advancement of cryptosome in the world of drug delivery.This review would help researchers involved in the field of vesicular drug delivery.

An efficient and long-acting local anesthetic: ropivacaine-loaded lipid-polymer hybrid nanoparticles for the control of pain.

PurposeLocal anesthetics are used clinically for the control of pain following operation (including gastrointestinal surgery) or for the management of other acute and chronic pain. This study aimed to develop a kind of lipid-polymer hybrid nanoparticles (LPNs), which were constructed using poly(ethylene glycol)-distearoylphosphatidylethanolamine (PEG-DSPE) as the hydrophilic lipid shell and poly-ε-caprolactone (PCL) as the hydrophobic polymeric core.MethodsRopivacaine (RPV) was entrapped in the LPNs (RPV-LPNs) and the physicochemical and biochemical properties such as size, zeta potential, drug release, and cytotoxicity were studied. The long-lasting effects and safety aspects of the LPNs were evaluated in vitro and in vivo.ResultsThe particle size and zeta potential of RPV-LPNs were 112.3±2.6 nm and −33.2±3.2 mV, with an entrapment efficiency (EE) of 90.2%±3.7%. Ex vivo permeation efficiency of LPNs was better than the drug solution. The RPV-LPNs exhibited a long-lasting in vivo anesthesia effect in both rats and mice.ConclusionConsidering the low cytotoxicity, the LPNs prepared here could be used as an efficient local anesthetic for the control of pain.

Smart nanocarrier based on PEGylated hyaluronic acid for deacetyl mycoepoxydience: High stability with enhanced bioavailability and efficiency

Deacetyl mycoepoxydience (DM) nanocrystals core were stabilized by the folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG2000-FA) as the active-targeting stabilizer and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as the reversion of multidrug resistance stabilizer, respectively. The DM nanocrystals was acted as the core and shelled by the polyethylene glycol-hyaluronic acid (PEG-HA). The optimal core-shell system demonstrated superior stability at 4 °C for 6 weeks by the stability study and higher dissolution velocity. Cytotoxicity in vitro and cell proliferation inhibition was evaluated by MCF-7 cells line. Furthermore, the core-shell nanocrystals revealed a concentration- and time-dependent cytotoxicity activity and enhanced the cell proliferation inhibition. Pharmacokinetic studies in rabbits showed core-shelled DM nanocrystals significantly increased AUC and t1/2 and reduced CLz compared to the DM solution for intravenous delivery. Results indicated that core-shell nanocrystals nanogel was successfully established with higher stability and the bioavailability of DM with higher safety was improved.

Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomes

This study aimed to investigate the ability of the novel materials D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate (TPOS) to construct pH-sensitive liposomes. TPOS was initially synthesized and characterized by TLC, FTIR, and 1H-NMR. The buffering capacity of polyethylene glycol- distearoyl phosphatidylethanolamine (PEG-DSPE) and TPOS was determined by acid-base titration, and TPOS displayed a slower downtrend and gentler slope of titration curve than PEG-DSPE within pH 7.4–5.0. Studies on the in vitro drug release demonstrated that TPOS modified docetaxel (DOC) liposomes (TPOS-DOC-L) had a slower drug-release rate at pH 7.4 similar to PEGylated-DOC liposomes (PEG-DOC-L), whereas the release rate reached approximately 86.92% ± 1.69% at pH 6.4. In vitro cellular uptake assays by microplate reader, and flow cytometry revealed that TPOS modified coumarin 6 liposomes (TPOS-C6-L) had stronger cellular uptake at pH 6.4 than that at pH 7.4 (P < 0.01). Conversely, for PEGylated C6 liposomes (PEG-C6-L) and conventional C6 liposomes (C6-L), very similar cellular uptakes were exhibited at different pH values. Confocal laser scanning microscopy images showed that PEG-C6-L and C6-L were mainly located in lysosomes. By contrast, TPOS-C6-L showed broader cytoplasmic release and distribution at 4 h. MTT assay showed that the cytotoxicity of TPOS-DOC-L was similar to that of PEG-DOC-L and conventional DOC liposomes (DOC-L) at the same DOC concentration and at pH 7.4, but was much lower than those at pH 6.4 after 48 h of incubation. The apoptosis of PEG-DOC-L and DOC-L had no remarkable improvement with decreased pH from 7.4 to 6.4. Meanwhile, TPOS-DOC-L significantly induced the apoptosis of HeLa cells with decreased pH. Therefore, TPOS can be a biomaterial for the construction of a pH-sensitive drug delivery system.

Cryoprotectant choice and analyses of freeze-drying drug suspension of nanoparticles with functional stabilisers

Freeze-drying is an effective way to improve long-term physical stability of nanosuspension in drug delivery applications. Nanosuspension also known as suspension of nanoparticles. In this study, the effect of freeze-drying with different cryoprotectants on the physicochemical characteristics of resveratrol (RSV) nanosuspension and quercetin (QUE) nanosuspension was evaluated. D-α-tocopheryl polyethylene glycol succinate (TPGS) and folate-modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) were selected as functional stabilisers formulated nanosuspension which were prepared by anti-solvent precipitation method. RSV nanoparticle size and QUE nanoparticle size were about 210 and 110 nm, respectively. The AFM and TEM results of nanosuspension showed uniform and irregular shape particles. After freeze-drying, the optimal concentration of four cryoprotectants was determined by the particle size of re-dispersed nanoparticles. The dissolution profile of drug nanoparticle significantly showed approximately at a 6–8-fold increase dissolution rate. Moreover, TPGS and DSPE-PEG-FA stabilised RSV nanosuspension and QUE nanosuspension samples showed better effect on long-term physical stability.

αvβ3 integrin receptor specific peptide modified, salvianolic acid B and panax notoginsenoside loaded nanomedicine for the combination therapy of acute myocardial ischemia

PurposeTo achieve the combination therapy of acute myocardial ischemia, arginyl-glycyl-aspartic acid (RGD) conjugated lipid was synthesized and RGD modified, salvianolic acid B (Sal B) and panax notoginsenoside (PNS) co-loaded lipid-polymer hybrid nanoparticles (RGD-S/P-LPNs) was fabricated an evaluated. MethodsRGD was conjugated to distearoyl phosphatidylethanolamine-polyethylene glycol (DSPE-PEG-NH2) through amide linkage. Lipid-polymer hybrid nanoparticles (LPNs) were fabricated by nanoprecipitation method. RGD-S/P-LPNs was characterized in terms of morphology, size, charge, drug loading, entrapment, stability, drug release and cytotoxicity in vitro. Cardiac distribution, pharmacokinetics study and infarct therapy effect were evaluated in vivo. ResultsThe LPNs are generally spherical in shape with uniform size distribution, have sizes of 100–200nm and zeta potentials range from −30.7∼ −39.8. In vitro release behaviors of drugs loaded LPNs are in a sustained release manner, which does not exhibit obviously cytotoxicity against H9c2 cardiomyocytes. RGD-S/P-LPNs group shows the most significant cardiac distribution and infarct therapy effect in vivo. ConclusionThe results illustrated that RGD modified dual drugs co-loaded LPNs are stable, sustained release carriers. Cardiac distribution, pharmacokinetics, and infarct therapy effect results suggested that the RGD-S/P-LPNs could improve the in vivo therapeutic efficacy of the double drugs.

In vitro and in vivo evaluation of targeting tumor with folate-based amphiphilic multifunctional stabilizer for resveratrol nanosuspensions

Resveratrol (RSV) nanosuspensions, with long term stability and targeting delivery ability, were designed and demonstrated by in vitro and in vivo model. The folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA), as target delivery carrier, was synthesized and confirmed by FTIR and 1H NMR. D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and DSPE-PEG-FA used as stabilizers formed two RSV nanosuspensions (RSV-NA and RSV-NB), which were prepared by anti-solvent precipitation method and optimized by central composite design-response surface model (CCD-RSM). The morphology of RSV nanosuspensions showed flake shapes and spherical shapes by SEM. And the distribution of particles was uniform by TEM and AFM. The two RSV nanosuspensions displayed an amorphous state, by XRPD and DSC determination. At room temperature, the optimum RSV nanosuspensions showed long term stability for 20days. The cell proliferation and morphology study revealed that the RSV nanosuspensions significantly enhanced the in vitro cytotoxicity against A549 cells in a dose- and time-dependent manner. The recommended safe concentration was 5μM for in vitro study. In vivo studies of the two nanosuspensions also displayed higher antitumor efficacy by reduced tumor volume and weight. Compared with the saline group, the tumor inhibition ratio of the RSV-NA was 61.53±18.36% and RSV-NB was 64.61±21.13%. The mice weight of the RSV-NA group and RSV-NB group was also maintained constant increasing. These results demonstrated that TPGS and DSPE-PEG-FA could be used as stabilizers for stable RSV nanosuspensions formulation with the potentiality for targeting delivery to human alveolar carcinoma cells with high stability and efficacy.