Systematic review of the mechanisms and evidence behind the hypocholesterolaemic effects of HPMC, pectin and chitosan in animal trials.

Dietary fibres have diverse mechanisms in reducing plasma cholesterol, which could be useful for treating high levels of low-density lipoprotein cholesterol (LDL-C). The objective of this review is to determine the state of the evidence for the cholesterol-lowering effects of three selected fibres and their mechanisms, using the most recent animal trials. Therefore, a systematic review was conducted for hydroxypropyl methylcellulose (HPMC), pectin and chitosan in Pubmed, Embase and the Cochrane Library. All fibres reviewed reduced total cholesterol, very low-density lipoprotein cholesterol (VLDL-C) and LDL-C. Pectin gave a small, and chitosan an impressive rise in high-density lipoprotein cholesterol (HDL-C). A limitation of this study is the variety of animal models, each with distinct cholesterol profiles. Possible publication bias was also detected. In conclusion, chitosan seems to be the most promising of the studied fibres. A dietary fibre could be designed that yields the best cholesterol-lowering effect, using experiences in tailoring physicochemical properties and primarily exploiting the biophysical mechanisms of action.

Drug release from PLGA microspheres attached to solids using supercritical CO2.

Functionalization of a porous orthopedic implant with dexamethasone, a widely used anti-inflammatory drug, encapsulated within a biodegradable polymer for controlled release could help reduce or eliminate the inflammation response by the local tissue. In this research, we investigated the possibility of using supercritical carbon dioxide (CO2) for attaching dexamethasone-loaded PLGA (polylactic-co-glycolic acid) microspheres to porous CoCrMo alloy for continuous delivery of dexamethasone. Supercritical CO2 has been shown to be effective for attachment of PLGA microspheres to glass plates and porous CoCrMo alloy. Attached microspheres showed similar dexamethasone release profiles but different magnitude of burst release. Microspheres attached to the porous alloy samples using supercritical CO2 at 10 bar and 40 °C for 30 min showed a release profile similar to that of the nonattached microspheres. The microsphere morphology and the release profiles of microspheres attached to the glass plates and to the porous alloy samples suggest that dexamethasone burst release is enhanced by PLGA swelling at higher CO2 pressures and better dispersion of microspheres. This study shows that microspheres can be incorporated into porous solids using supercritical CO2, allowing for a wide variety of drug-biodegradable polymer formulations prepared using the proven emulsion/solvent evaporation method to be tested.

Preparation and physicochemical characterization of supercritically dried insulin-loaded microparticles for pulmonary delivery.

In the search for non-invasive delivery options for the increasing number of therapeutic proteins, pulmonary administration is an attractive route. Supercritical fluid (SCF) drying processes offer the possibility to produce dry protein formulations suitable for inhalation. In this study, insulin-loaded microparticles suitable for pulmonary administration were prepared and characterized. N-Trimethyl chitosan (TMC), a polymeric mucoadhesive absorption enhancer and dextran, a non-permeation enhancer, were used as carriers for insulin. The particles were prepared by spraying an acidic water/DMSO solution of insulin and polymer into supercritical carbon dioxide. The mean size of the particles was 6-10microm (laser diffraction analysis) and their volume median aerodynamic diameter ca. 4microm (time-of-flight analysis). The particles had a water content of ca. 4% (w/w) (Karl-Fischer), and neither collapsed nor aggregated after preparation and storage. In the freshly prepared dried insulin powders, no insulin degradation products were detected by HPLC and GPC. Moreover, the secondary and tertiary structures of insulin as determined by circular dichroism and fluorescence spectroscopy were preserved in all formulations. After one-year storage at 4 degrees C, the particle characteristics were maintained and the insulin structure was largely preserved in the TMC powders. In conclusion, SCF drying is a promising, protein-friendly technique for the preparation of inhalable insulin-loaded particles.

Diphtheria toxoid-containing microparticulate powder formulations for pulmonary vaccination: preparation, characterization and evaluation in guinea pigs.

In this study, the potential of N-Trimethyl chitosan (TMC, degree of quaternization 50%) and dextran microparticles for pulmonary delivery of diphtheria toxoid (DT) was investigated. The antigen-containing microparticles were prepared by drying of an aqueous solution of polymer and DT through a supercritical fluid (SCF) spraying process. The median volume diameter of the dry particles, as determined by laser diffraction analysis, was between 2 and 3 microm and the fine particle mass fractions smaller than 5 microm, as determined by cascade impactor analysis, were 35 and 56% for the dextran and TMC formulations, respectively. The water content of the particles as measured by Karl-Fischer titration was 2-3% (w/w). Pulmonary immunization with DT-TMC microparticles containing 2 or 10 Lf of DT resulted in a strong immunological response as reflected by the induction of IgM, IgG, IgG subclasses (IgG1 and IgG2) antibodies as well as neutralizing antibody titers comparable to or significantly higher than those achieved after subcutaneous (SC) administration of alum-adsorbed DT (2 Lf). Moreover, the IgG2/IgG1 ratio after pulmonary immunization with DT-TMC microparticles was substantially higher as compared to SC administered alum-adsorbed DT. In contrast, pulmonarily administered DT-dextran particles were poorly immunogenic. Among the tested formulations only pulmonarily administered DT-containing TMC microparticles induced detectable pulmonary secretory IgA levels. In conclusion, in this paper it is demonstrated that TMC microparticles are a potent new delivery system for pulmonary administered DT antigen.