ABSTRACT
A crosslinked alginate microparticle system for the targeting to the lymphatic system by Peyer's patches (PP) uptake was designed in order to improve the oral absorption of Polymyxin B (PMB). To verify mucoadhesion and PP uptake, microparticles labelled with fluorescein isothiocyanate (FITC) were prepared by spray-drying technique and crosslinking reactions with calcium ions and chitosan (CS), in vitro characterized and assayed by an ex vivo method. Microparticles showed a size less then 3 microm, an antibiotic loading level of 11.86 +/- 0.70%, w/w, a sustained drug release behaviour in simulated gastro-intestinal (GI) fluids and a preserved biological activity throughout the manufacture. The ex vivo study was performed by a perfusion method on intestinal tracts of just sacrificed adult rats. The recovered samples were analysed by epifluorescence microscope for mucoadhesion and PP uptake and by microbiological analysis for antibiotic activity preservation, providing evidence of mucoadhesion at the level of both PP and non-PP epithelium, uptake by PP and PMB microbiological activity in PP tissue. Furthermore, the study revealed the involvement of transport pathways across villous enterocytes.
Subject(s)
Alginates/pharmacology , Anti-Bacterial Agents/administration & dosage , Polymyxin B/administration & dosage , Administration, Oral , Animals , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/pharmacokinetics , Excipients , Fluorescein-5-isothiocyanate , Fluorescent Dyes , Intestine, Small/drug effects , Intestine, Small/metabolism , Microscopy, Confocal , Microscopy, Electron, Scanning , Microscopy, Fluorescence , Nanoparticles , Particle Size , Perfusion , Polymyxin B/analysis , Polymyxin B/pharmacokinetics , Rats , Rats, Sprague-DawleyABSTRACT
The aim of this study was to investigate the incorporation into lipospheres of the complex between hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and the sunscreen agent, butyl methoxydibenzoylmethane (BMDBM) and to examine the influence of this system on the sunscreen photostability. The formation of the inclusion complex was confirmed by thermal analysis and powder X-ray diffraction. Lipid microparticles loaded with free BMDBM or its complex with HP-beta-CD were prepared using tristearin as the lipid material and hydrogenated phosphatidylcholine as the emulsifier. The obtained lipospheres were characterized by scanning electron microscopy and differential scanning calorimetry. The microparticle size (15-40 microm) was not affected by the presence of the complex. Release of BMDBM from the lipospheres was lower when it was incorporated as inclusion complex rather than as free molecule. Unencapsulated BMDBM, its complex with HP-beta-CD, the sunscreen-loaded lipospheres or the lipoparticles containing the BMDBM/HP-beta-CD complex, were introduced into a model cream (oil-in-water emulsion) and irradiated with a solar simulator. The photodegradation studies showed that all the examined systems achieved a significant reduction of the light-induced decomposition of the free sunscreen agent (the BMDBM loss decreased from 28.9 to 17.3-15.2%). However, photolysis experiments performed during 3 months storage of the formulations, demonstrated that the photoprotective properties of the HP-beta-CD complex and of BMDBM alone-loaded lipospheres decreased over time, whereas the microencapsulated HP-beta-CD/BMDBM complex retained its photostabilization efficacy. Therefore, incorporation in lipid microparticles of BMDBM in the cyclodextrin complex form is more effective in enhancing the sunscreen photostability than the complex alone or the liposphere-entrapped free BMDBM.
Subject(s)
Alkanes/chemistry , Chalcones/chemistry , Excipients/chemistry , Liposomes , Sunscreening Agents/chemistry , beta-Cyclodextrins/chemistry , 2-Hydroxypropyl-beta-cyclodextrin , Alkanes/radiation effects , Chalcones/radiation effects , Drug Compounding , Drug Stability , Emulsions , Particle Size , Phosphatidylcholines/chemistry , Photolysis , Propiophenones , Solubility , Sunscreening Agents/radiation effects , Time Factors , Triglycerides/chemistry , Ultraviolet RaysABSTRACT
The incorporation of butyl-methoxydibenzoylmethane (BMDBM), one of the most efficient and frequently used UV-A blockers, into lipospheres was examined in order to decrease the light-induced sunscreen degradation. Lipospheres, obtained by the melt technique and using tristearin as the lipid material and hydrogenated phosphatidylcholine as the emulsifier, showed proper features in terms of size (10-40 microm), BMDBM loading level (21.63% +/- 0.90%, w/w) and physical state. Photolysis studies, involving irradiation of lipospheres with simulated sunlight before and after their introduction in emulsion formulations, demonstrated a relevant enhancement of the encapsulated sunscreen photostability in comparison with unencapsulated BMDBM.
