Effect of vesicle size on tissue localization and immunogenicity of liposomal DNA vaccines.

The formulation of plasmid DNA (pDNA) in cationic liposomes is a promising strategy to improve the potency of DNA vaccines. In this respect, physicochemical parameters such as liposome size may be important for their efficacy. The aim of the current study was to investigate the effect of vesicle size on the in vivo performance of liposomal pDNA vaccines after subcutaneous vaccination in mice.

Evaluation of the high-pressure extrusion technique as a method for sizing plasmid DNA-containing cationic liposomes.

A promising strategy to improve the immunogenic potential of DNA vaccines is the formulation of plasmid DNA (pDNA) with cationic liposomes. In this respect, particle size may be of crucial importance. This study aimed at the evaluation of high-pressure extrusion as a method for sizing cationic liposomes after entrapment of pDNA.

Immunological risk of injectable drug delivery systems.

Injectable drug delivery systems (DDS) such as particulate carriers and water-soluble polymers are being used and developed for a wide variety of therapeutic applications. However, a number of immunological risks with serious clinical implications are associated with administration of DDS. These immunological events can compromise the efficacy and safety of these systems by changing the pharmacokinetics, biodistribution and targeting capability of DDS, and by inducing hypersensitivity reactions.

Opportunities and challenges in vaccine delivery.

This report is a distillation of the workshop 'Opportunities and Challenges in Vaccine Delivery', organised by EUFEPS/FIP and co-sponsored by AAPS and CRS, in Archamps, France, September 2008. The aim of this workshop was to bridge knowledge gaps between the different disciplines involved in the delivery of vaccines. Here, key challenges include target identification, mapping the needs and target population, the development and harmonisation of predictive read-out systems and surrogate markers for protection, and improving antigen immunogenicity, delivery and stability.

Photocytotoxicity of mTHPC (temoporfin) loaded polymeric micelles mediated by lipase catalyzed degradation.

Purpose: To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation.

Methods: Micelles of mPEG750-b-oligo(epsilon-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group were formed and loaded with mTHPC by the film hydration method. The cellular uptake of the loaded micelles, and their photocytotoxicity on human neck squamous carcinoma cells in the absence and presence of lipase were compared with free and liposomal mTHPC (Fospeg).

The effect of core composition in biodegradable oligomeric micelles as taxane formulations.

Docetaxel (DCTX) and paclitaxel (PTX) are very potent anti-cancer drugs, but the currently marketed formulations, Taxotere and Taxol, respectively, are associated with vehicle-related toxicity. An attractive alternative to formulate these hydrophobic cytotoxic agents are polymeric micelles. In this study, the loading of taxanes into oligomeric micelles composed of mPEG750-b-oligo(epsilon-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group was investigated.

A mechanistic study on the chemical and enzymatic degradation of PEG-Oligo(epsilon-caprolactone) micelles.

The chemical and enzymatic degradation of monodisperse oligo(epsilon-caprolactone) (OCL) and its amphiphilic block oligomer with methoxy poly(ethylene glycol) (mPEG) were investigated in order to obtain insight into the degradation of mPEG-b-OCL micelles. Hydrolytic degradation was studied as function of pH and dielectric constant of the medium, and enzymatic degradation was investigated at different enzyme and substrate concentrations. The degradation was monitored by HPLC and MS, and the micelle destabilization with DLS.

Pharmacokinetics of poly(hydroxyethyl-l-asparagine)-coated liposomes is superior over that of PEG-coated liposomes at low lipid dose and upon repeated administration.

'Stealth' liposomes with a poly(ethylene glycol) (PEG) coating are frequently studied for drug delivery and diagnostic purposes because of their prolonged blood circulation kinetics. However, several recent reports have demonstrated that PEG-liposomes are rapidly cleared at single low lipid doses (<1 micromol/kg) and upon repeated administration (time interval between the injections 5 days-4 weeks). Recently, poly(amino acid)-based stealth liposome coatings have been developed as alternative to the PEG-coating.

Poly(ethylene glycol)--oligolactates with monodisperse hydrophobic blocks: preparation, characterization, and behavior in water.

Methoxypoly(ethylene glycol)-b-oligo-L-lactate (mPEG-b-OLA) diblock oligomers with monodisperse OLA blocks were obtained by fractionation of polydisperse block oligomers using preparative HPLC. The fractionated oligomers were composed of an mPEG block with a molecular weight of 350, 550, or 750 and an OLA block with a degree of polymerization of 4, 6, 8, or 10. The diblock oligomers with a low PEG content were fully amorphous, with glass transition temperatures ranging from -60 to -20 degrees C, indicating that the blocks were miscible.