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Drug delivery systems (DDSs) commonly employ arginine-glycine-aspartic acid (RGD) peptides with polyethylene glycol (PEG)-dependent enhanced permeability and retention (EPR) effect to optimise tumour-targeting. However, the PEG dilemma and integrin saturation obstacle are major challenges. To address these issues, we constructed a novel, nano-sized DDS by encapsulating doxorubicin (DOX)-loaded folic acid derivatives of polyamidoamine dendrimer (PAMAM G5.0) in cyclic RGD-tyrosine-lysine pentapeptide (c[RGDyK])-modified liposomes (RGD-SL[FND/DOX]), prepared using thin-film hydration, film-dispersion and hydration-sonication. The liposomes were PEGylated, sterically stabilised and pH-sensitive. In vitro, RGD-SL[FND/DOX] showed pH-sensitive holistic FND/DOX release, and pH-dependent uptake and cytotoxicity in human cancer KB cells. At pH 7.4, RGD-SL[FND/DOX] demonstrated greater cellular uptake and cytotoxicity than relevant control formulations (except FND/DOX) did, although this advantage disappeared at pH 6.5. In vivo, RGD-SL[FND/DOX] inhibited S180 sarcoma xenografted tumour growth in Kunming mice more effectively than FND/DOX did. These findings demonstrate the feasibility of constructing double-stage tumour-targeting nano-sized DDSs such as RGD-SL[FND/DOX]. c[RGDyK] and the EPR effect, facilitated by the particle size (about 110 nm) and PEGylation, helped to target the DDS to the tumour tissue, while the subsequent pH-dependent release of FND/DOX and folic acid-mediated endocytosis specifically targeted the tumour cells, thereby overcoming the PEG dilemma and integrin saturation obstacle.

Liposomes as a drug carrier is easy to form aggregation and cause drug leakage in vitro. In addition, the degradation and elimination in vivo happens frequently to reduce its delivery activity. Development and application of liposomes are restricted by the instability. The appropriate techniques and methods are great important in the study of pharmaceutical stability of liposomes. In this paper, the techniques and methods are reviewed on pharmaceutical stability evaluation of liposomes, which was done from physical, chemical and biological stability for the difference in stability of liposomes. The research strategies for establishing the stability evaluation system and improving the value of liposomes have been discussed to make full therapeutic advantage of it.

Non-small cell lung cancer (NSCLC) is a serious threat to human health, and 40%-80% of NSCLCs express high levels of epidermal growth factor receptor (EGFR). GE11 is a novel peptide and exhibits high affinity for EGFR binding. The aim of this study was to construct and evaluate GE11-modified liposomes for targeted drug delivery to EGFR-positive NSCLC. Doxorubicin, a broad-spectrum antitumor agent, was chosen as the payload. GE11 was conjugated to the distal end of DSPE-PEG2000-Mal by an addition reaction with a conjugation efficiency above 90%. Doxorubicin-loaded liposomes containing GE11 (GE11-LP/DOX) at densities ranging from 0% to 15% were prepared by combination of a thin film hydration method and a post insertion method. Irrespective of GE11 density, the physicochemical properties of these targeted liposomes, including particle size, zeta potential, and drug entrapment efficiency, were nearly identical. Interestingly, the cytotoxic effect of the liposomes on A549 tumor cells was closely related to GE11 density, and liposomes with 10% GE11 had the highest tumor cell killing activity and a 2.6-fold lower half maximal inhibitory concentration than that of the nontargeted counterpart (PEG-LP/DOX). Fluorescence microscopy and flow cytometry analysis revealed that GE11 significantly increased cellular uptake of the liposomes, which could be ascribed to specific EGFR-mediated endocytosis. It was found that multiple endocytic pathways were involved in entry of GE11-LP/DOX into cells, but GE11 assisted in cellular internalization mainly via the clathrin-mediated endocytosis pathway. Importantly, the GE11-modified liposomes showed enhanced accumulation and prolonged retention in tumor tissue, as evidenced by a 2.2-fold stronger mean fluorescence intensity in tumor tissue than the unmodified liposomes at 24 hours. In summary, GE11-modified liposomes may be a promising platform for targeted delivery of chemotherapeutic drugs in NSCLC.

It is generally believed that liposomes modified with polyethylene glycol (PEG) have no or lower immunogenicity. However, based on many recent literatures, when the PEGylated liposomes were repeatedly applied to the same animal, the immune responses occurred. The first injection of PEGylated liposomes resulted in a reduction in the circulation time and an increase in hepatic and splenic accumulation of the second dose of PEGylated liposomes in a time-interval, which was called "accelerated blood clearance (ABC)" phenomenon. Such immunogenicity of PEGylated liposomes presents a barrier in the research of liposomal formulations and their use in the clinics. This review focused on the definition, the method of verification, the development of the reason for ABC phenomenon, influencing factors of ABC phenomenon, and discussed if other PEGylated nanocarriers also induce ABC phenomenon.

Objective: To prepare the long-circulating nanoliposomes of curcumin., Method: The long-circulating nanoliposomes were prepared by ethanol infusion and the encapsulation efficiency was determindated by the mini-column centrifugation. The effect of some factors on the encapsulation efficiency, such as the buffer solutions, the weight ratio of curcumin to SPC, the weight ratio of SPC to Chol, the pH of buffer solution and the iron strength of water phase, was investigated respectively. Then the formulation was optimized by orthogonal design., Result: The encapsulation efficiency of the curcumin liposomes was (88.27 +/- 2.16)%, and the average diameter of the liposomes was (136 +/- 18) nm. There was no change on encapsulation efficency within 30 d., Conclusion: The preparation of curcumin liposomes was easy and practicable and the pharmaceutical characterization showed that the curcumin liposomes are stable.

Polyethylene glycol (PEG) lipid derivatives could increase the stability of liposomes in vivo and in vitro and prolong the circulation time of liposomes in vivo. However, the chemical bond between PEG and lipid was so stable that liposomes modified with traditional PEG-lipid derivatives could not release their contents at targeted tissue immediately and the pharmacodynamic effect was reduced. The concept of cleavable PEG-lipid was raised in recent years and these PEG-lipid derivatives could break under physiological or pathological condition. The cleavable PEG-lipid derivatives could prolong the circulation time of liposomes, and after arriving at targeted location, PEG fragment had cleaved from the surface of liposomes, so liposomes could bind with pathological cells and release contents into cells. Removal of the protective polymer layer is necessary once the liposome close to the tumour to allow to fuse and release drug. Attempts have been made to increase the circulation time and reconstitute the cellular affinity of liposomes by incorporating PEG-lipid derivatives. This review focused on the kinds of cleavable PEG-lipid derivatives, types of cleavage, the application feature to liposomes and the advantages and localizations.

Ferulic acid (FA) was loaded into liposomes via calcium acetate gradient with (80.2 +/- 5.2)% entrapment efficiency. The average sizes of blank liposome and FA liposome were about 155 nm and 154 nm, respectively. The zeta potential of blank liposome and FA liposome were (13.14 +/- 1.67) mV and (4.12 +/- 0.05) mV, respectively. Unilamellar vesicles were present in freeze-fracture electron microscopy. In the pharmacodynamic studies, the protective effect of liposomal ferulic acid on tBHP-challenged U937 cells was measured with the morphology of cell injury, mitochondrial transmembrane potential alternation and cell viability assay used as index. The results of MTT assay, microscopy indicated that FA liposomes exhibited greater antioxidant activity than FA solution on U937 cell.

Abstract: This paper described the synthesis of a novel galactosylated lipid with mono-galactoside moiety, (5-Cholesten-3β-yl) 4-oxo-4-[2-(lactobionyl amido) ethylamido] butanoate (CHS-ED-LA), and the targetability of doxorubicin (DOX), a model drug, in liposomes containing 10% mol/mol CHS-ED-LA (galactosylated liposomes, GalL) to the liver was studied. The weighted-average overall drug targeting efficiency (Te *) was used to evaluate the liver targetability of GalL DOX. The results showed that GalL DOX gave a relatively high (Te *)liver value of 64.6%, while DOX in conventional liposome (CL DOX) only gave a (Te *)liver value of 21.8%. In the liver, the GalL DOX was mainly taken up by parenchymal cells (88% of the total hepatic uptake). Moreover, preinjection of asialofetuin significantly inhibited the liver uptake of GalL DOX (from 70 to 12% of the total injected dose). It was suggested that liposomes containing such novel galactosylated lipid, CHS-ED-LA, had a great potential as drug delivery carriers for hepatocyte-selective targeting. [Copyright &y& Elsevier]