The long-circulating effect of pegylated nanoparticles revisited via simultaneous monitoring of both the drug payloads and nanocarriers

The long-circulating effect is revisited by simultaneous monitoring of the drug payloads and nanocarriers following intravenous administration of doxorubicin (DOX)-loaded methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) nanoparticles. Comparison of the kinetic profiles of both DOX and nanocarriers verifies the long-circulating effect, though of limited degree, as a result of pegylation. The nanocarrier profiles display fast clearance from the blood despite dense PEG decoration; DOX is cleared faster than the nanocarriers. The nanocarriers circulate longer than DOX in the blood, suggesting possible leakage of DOX from the nanocarriers. Hepatic accumulation is the highest among all organs and tissues investigated, which however is reversely proportionate to blood circulation time. Pegylation and reduction in particle size prove to extend circulation of drug nanocarriers in the blood with simultaneous decrease in uptake by various organs of the mononuclear phagocytic system. It is concluded that the long-circulating effect of mPEG-PCL nanoparticles is reconfirmed by monitoring of either DOX or the nanocarriers, but the faster clearance of DOX suggests possible leakage of a fraction of the payloads. The findings of this study are of potential translational significance in design of nanocarriers towards optimization of both therapeutic and toxic effects.

Adapting liposomes for oral drug delivery

Liposomes mimic natural cell membranes and have long been investigated as drug carriers due to excellent entrapment capacity, biocompatibility and safety. Despite the success of parenteral liposomes, oral delivery of liposomes is impeded by various barriers such as instability in the gastrointestinal tract, difficulties in crossing biomembranes, and mass production problems. By modulating the compositions of the lipid bilayers and adding polymers or ligands, both the stability and permeability of liposomes can be greatly improved for oral drug delivery. This review provides an overview of the challenges and current approaches toward the oral delivery of liposomes.

Biomimetic thiamine- and niacin-decorated liposomes for enhanced oral delivery of insulin

Biomimetic nanocarriers are emerging as efficient vehicles to facilitate dietary absorption of biomacromolecules. In this study, two vitamins, thiamine and niacin, are employed to decorate liposomes loaded with insulin, thus facilitating oral absorption vitamin ligand-receptor interactions. Both vitamins are conjugated with stearamine, which works to anchor the ligands to the surface of liposomes. Liposomes prepared under optimum conditions have a mean particle size of 125-150 nm and an insulin entrapment efficiency of approximately 30%-36%. Encapsulation into liposomes helps to stabilize insulin due to improved resistance against enzymatic disruption, with 60% and 80% of the insulin left after 4 h when incubated in simulated gastric and intestinal fluids, respectively, whereas non-encapsulated insulin is broken down completely at 0.5 h. Preservation of insulin bioactivity against preparative stresses is validated by intra-peritoneal injection of insulin after release from various liposomes using the surfactant Triton X-100. In a diabetic rat model chemically induced by streptozotocin, both thiamine- and niacin-decorated liposomes showed a comparable and sustained mild hypoglycemic effect. The superiority of decorated liposomes over conventional liposomes highlights the contribution of vitamin ligands. It is concluded that decoration of liposomes with thiamine or niacin facilitates interactions with gastrointestinal vitamin receptors and thereby facilitates oral absorption of insulin-loaded liposomes.

Preparation and in vitro evaluation of methoxy polyethylene glycol-polycaprolactone nanoparticles loading a water-quenching fluorescent probe / 第二军医大学学报

Objective To prepare methoxy polyethylene glycol (mPEG)-polycaprolactone (PCL) nanoparticles loading a water-quenching fluorescent probe and to evaluate its in vitro characteristics and stability.Methods PCL nanoparticles and mPEG-PCL nanoparticles with different mPEG chain lengths (mPEG5k,mPEG2k) loading the waterquenching fluorescent probe P2 were prepared by an emulsification/solvent evaporation method using PCL and mPEG-PCL as materials.In vitro characteristics such as morphology,particle size and distribution were evaluated.The P2 probe displayed fluorescent signals when encapsulated in the matrix of the nanoparticles,but quenched immediately when released into water.Based on this properties of P2 probe,the stability of various nanoparticles in different aqueous media was investigated.Results The prepared mPEG-PCL nanoparticles showed a particle size of about 200 nm,narrow size distribution,polydispersity index below 0.06 and near neutral surface potentials with spherical morphology and smooth surfaces.In buffers of different pHs and simulated bio-relevant media,all nanoparticles showed very good stability without significant change in particle size,polydispersity index and fluorescence intensity.Conclusion mPEG-PCL nanoparticles have promising in vitro characteristics and robust stability.It is fast and convenient to monitor the stability of nanoparticles by using the water-quenching probe.