Qiang Peng

Preformed albumin corona, a protective coating for nanoparticles based drug delivery system.

The non-specific interaction between nanoparticles (NPs) and plasma proteins occurs immediately after NPs enter the blood, resulting in the formation of the protein corona that thereafter replaces the original NPs and becomes what the organs and cells really see. Consequently, the in vivo fate of NPs and the biological responses to the NPs are changed. This is one substantial reason for the two main problems of the NPs based drug delivery system, i.e. nanotoxicity and rapid clearance of NPs from the blood after intravenous injection. Here, we demonstrate the successful application of the preformed albumin corona in inhibiting the plasma proteins adsorption and decreasing the complement activation, and ultimately in prolonging the blood circulation time and reducing the toxicity of the polymeric PHBHHx NPs. Since the interaction of proteins with various nano-materials and/or -particles is ubiquitous, pre-forming albumin corona has a great potential to be a versatile strategy for optimizing the NPs based drug delivery system.

A rapid-acting, long-acting insulin formulation based on a phospholipid complex loaded PHBHHx nanoparticles.

The application of poly(hydroxybutyrate-co-hydroxyhexanoate) (PHBHHx) for sustained and controlled delivery of hydrophilic insulin was made possible by preparing insulin phospholipid complex loaded biodegradable PHBHHx nanoparticles (INS-PLC-NPs). The INS-PLC-NPs produced by a solvent evaporation method showed a spherical shape with a mean particle size, zeta potential and entrapment efficiency of 186.2 nm, -38.4 mv and 89.73%, respectively. In vitro studies demonstrated that only 20% of insulin was released within 31 days with a burst release of 5.42% in the first 8 h. The hypoglycaemic effect in STZ induced diabetic rats lasted for more than 3 days after the subcutaneous injection of INS-PLC-NPs, which significantly prolonged the therapeutic effect compared with the administration of insulin solution. The pharmacological bioavailability (PA) of INS-PLC-NPs relative to insulin solution was over 350%, indicating that the bioavailability of insulin was significantly enhanced by INS-PLC-NPs. Therefore, the INS-PLC-NPs system is promising to serve as a long lasting insulin release formulation, by which the patient compliance can be enhanced significantly. This study also showed that phospholipid complex loaded biodegradable nanoparticles (PLC-NPs) have a great potential to be used as a sustained delivery system for hydrophilic proteins to be encapsulated in hydrophobic polymers.

Injectable and biodegradable thermosensitive hydrogels loaded with PHBHHx nanoparticles for the sustained and controlled release of insulin.

Biodegradable PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) nanoparticles containing insulin phospholipid complex were loaded in chitosan-based thermosensitive hydrogels for long-term sustained and controlled delivery of insulin. The injectable hydrogels, prepared by adding β-glycerophosphate disodium salt (GP) solution to chitosan (CS) solution under stirring, showed a rapid solution-to-gel transition at 37 °C, a porous structure and a comparative degradation and swelling rate in vitro. In the in vitro release studies, only 19.11% of total insulin was released from the nanoparticle-loaded hydrogel (NP-CS/GP) within 31 days. However, 96.41% of total insulin was released from the free insulin-loaded hydrogel (INS-CS/GP) within 16 days. Most importantly, the hypoglycemic effect of NP-CS/GP following subcutaneous injection in diabetic rats lasted for >5 days, much longer than the effect caused by INS-CS/GP or other long-acting insulin formulations. The pharmacological availability of NP-CS/GP relative to INS-CS/GP was 379.85%, indicating that the bioavailability of insulin was significantly enhanced by NP-CS/GP gels. Therefore, biodegradable and thermosensitive NP-CS/GP gels have great potential for use in novel ultralong-acting insulin injections. In addition, the NP-loaded hydrogel system also paves the way for long-term delivery of other proteins and peptides.

Mechanisms of Phospholipid Complex Loaded Nanoparticles Enhancing the Oral Bioavailability

The purpose of the present study was to study the mechanisms of salvianolic acid B phospholipid complex loaded nanoparticles (SalB-PLC-NPs) enhancing the oral bioavailability of SalB by in situ perfusion model in rats and to evaluate the potential of phospholipid complex loaded nanoparticles (PLC-NPs) serving as an efficient oral delivery system to enhance the bioavailability of highly water-soluble drugs. SalB-PLC-NPs, prepared by a solvent evaporation method, exhibited a spherical shape with a mean particle size and a zeta potential of 112.2 nm and -44.2 mV, respectively. The drug entrapment efficiency and drug loading were 86.19% and 3.21%, respectively. The lyophilized SalB-PLC-NPs, prepared with 10% maltose as the cryoprotectant, presented sustained release profiles in artificial gastric juice (0.1 M HCl with pH 1.2) and intestinal juice (PBS with pH 6.8 and 7.4). The absorption mechanisms were studied using a modified in situ perfusion method in rats, which showed the segment dependent absorption characteristics of SalB, SalB-PLC as well as SalB-PLC-NPs. The greatest absorption was obtained when SalB-PLC-NPs were perfused in colon. The possibility of intestinal lymphatic transport of SalB-PLC-NPs was investigated using mesenteric lymph vessel cannulation. Microscope (fluorescence and natural light) observation of lymph indicated that nanoparticles underwent intestinal lymphatic transport. In conclusion, the enhanced oral bioavailability of SalB was contributed to both the PLC and NPs. Importantly, our studies indicate that PLC-NPs may be a promising delivery system to enhance the oral bioavailability of highly water-soluble drugs.

Preparation, characterization, and in vivo evaluation of a self-nanoemulsifying drug delivery system (SNEDDS) loaded with morin-phospholipid complex.

Background As a poorly water-soluble drug, the oral application of morin is limited by its low oral bioavailability. In this study, a new self-nanoemulsifying drug delivery system (SNEDDS), based on the phospholipid complex technique, was developed to improve the oral bioavailability of morin. Methods Morin-phospholipid complex (MPC) was prepared by a solvent evaporation method and characterized by infrared spectroscopy and X-ray diffraction. After formation of MPC, it was found that the liposolubility of morin was significantly increased, as verified through solubility studies. An orthogonal design was employed to screen the blank SNEDDS, using emulsifying rate and particle size as evaluation indices. Ternary phase diagrams were then constructed to investigate the effects of drug loading on the self-emulsifying performance of the optimized blank SNEDDS. Subsequently, in vivo pharmacokinetic parameters of the morin-phospholipid complex self-nanoemulsifying drug delivery system (MPC-SNEDDS) were investigated in Wistar rats (200 mg/kg of morin by oral administration). Results The optimum formulation was composed of Labrafil® M 1944 CS, Cremophor® RH 40, and Transcutol® P (3:5:3, w/w), which gave a mean particle size of approximately 140 nm. Oral delivery of the MPC-SNEDDS exhibited a significantly greater Cmax (28.60 μg/mL) than the morin suspension (5.53 μg/mL) or MPC suspension (23.74 μg/mL) (all P < 0.05). Tmax was prolonged from 0.48 to 0.77 hours and to 1 hour for MPC and MPC-SNEDDS, respectively. In addition, the relative oral bioavailability of morin formulated in the MPC-SNEDDS was 6.23-fold higher than that of the morin suspension, and was significantly higher than that of the MPC suspension (P < 0.05). Conclusion The study demonstrated that a SNEDDS combined with the phospholipid complex technique was a promising strategy to enhance the oral bioavailability of morin.

A novel submicron emulsion system loaded with vincristine–oleic acid ion-pair complex with improved anticancer effect: in vitro and in vivo studies

Background Vincristine (VCR), which is a widely used antineoplastic drug, was integrated with a submicron-emulsion drug-delivery system to enhance the anticancer effect. Methods After the formation of a VCR-oleic acid ion-pair complex (VCR-OA), the VCR-OA-loaded submicron emulsion (VCR-OA-SME), prepared by classical high-pressure homogenization, was characterized and its in vitro anticancer effects were evaluated. Results The submicron-emulsion formulation exhibited a homogeneous round shape. The mean particle size, zeta potential, and encapsulation efficiency were 157.6 ± 12.6 nm, −26.5 ± 5.0 mV and 78.64% ± 3.44%, respectively. An in vitro release study of the VCR-OA-SME revealed that 12.4% of the VCR was released within the first 2 hours (initial burst-release phase) and the rest of the drug was detected in the subsequent sustained-release phase. Compared with VCR solution, the pharmacokinetic study of VCR-OA-SME showed relatively longer mean residence time (mean residence time [0–∞] increased from 187.19 to 227.56 minutes), higher maximum concentration (from 252.13 ng/mL to 533.34 ng/mL), and greater area under the curve (area under the curve [0–∞] from 11,417.77 μg/L/minute to 17,164.34 μg/L/minute. Moreover, the VCR-OA-SME exhibited higher cytotoxicity (P < 0.05) on tumor cells by inducing cell arrest in the G2/M phase or even apoptosis (P < 0.05). Conclusion The VCR-OA-SME formulation in our study displayed great potential for an anticancer effect for VCR.

Hepatitis B virus preS1-derived lipopeptide functionalized liposomes for targeting of hepatic cells.

To enhance the liver-specific delivery, HBVpreS/2-48(myr) (HBVP), a synthetic HBVpreS-derived lipopeptide endowed with compelling liver tropism, was conjugated to PEGylated liposomes (HBVP-Lip) for hepatic cell-specific delivery. Compared with the non-targeted liposomes, a significantly higher amount of HBVP-Lip were taken up by the primary mice hepatocytes through a receptor-mediated endocytosis mechanism. The endocytosis inhibition assay demonstrated that the endocytosis of HBVP-Lip was mediated mainly by caveolin and clathrin. After systemic administration in mice, HBVP-Lip could be specifically internalized into hepatocytes efficaciously. Furthermore, the hepatoprotective effects of HBVP-Lip loaded with silybin (SLB) on carbon tetrachloride induced acute liver damage were remarkably stronger than the SLB solution and SLB loaded non-targeted liposomes. Preliminary safety results suggested that no acute systemic toxicity or immunotoxicity was observed after intravenous administration with HBVP-Lip. These results indicated that the HBVP-Lip could deliver the payloads to the hepatocytes with high specificity in vitro and in vivo, and raise new possibilities for liver-specific drug delivery systems, gene delivery systems, and bio-imaging systems.

A high-efficiency, low-toxicity, phospholipids-based phase separation gel for long-term delivery of peptides.

Peptide and protein drugs are currently under rapid development attributed to their high potency and efficacy in therapy. Their successful delivery, however, is highly limited by their short half-life, fast degradation and rapid clearance. Here, we present a high content phospholipids-based phase separation gel (PPSG), which is readily injectable due to its low initial viscosity and can rapidly transform into an in situ implant after injection upon exposure to an aqueous environment. A selected model peptide, octreotide acetate, is loaded into PPSG and achieves sustained release profiles for one month in rats. In addition, the local irritation caused by ethanol contained in PPSG is ethanol content-dependent and the irritation of PPSG with 70% phospholipids content can be eliminated by partially replacing ethanol with medium chain triglyceride. The mechanisms underlying phase transition of PPSG are based on water-insolubility of phospholipids. Our findings demonstrate that PPSG is a readily injectable, highly safe and efficient in situ forming implant for sustained delivery of peptides.

Independent effect of polymeric nanoparticle zeta potential/surface charge, on their cytotoxicity and affinity to cells.

Up to now, little research has been focussed on discovering how zeta potential independently affects polymeric nanoparticle (NP) cytotoxicity.

Electrospun P34HB fibres: a scaffold for tissue engineering

Amongst the fourth generation of PHAs is bio‐plasticpoly3‐hydroxybutyrate4‐hydroxybutyrate (P34HB); it is thus appropriate to perform novel research on its uses and applications. The main objective of this study was to determine whether electrospun P34HB fibres would accommodate viability, growth and differentiation of mouse adipose‐derived stem cells (mASCs).