Polymer-based particles against pathogenic fungi: A non-uptake delivery of compounds.

The therapy of life-threatening fungal infections is limited and needs urgent improvement. This is in part due to toxic side effects of clinically used antifungal compounds or their limited delivery to fungal structures. Until today, it is a matter of debate how drugs or drug-delivery systems can efficiently reach the intracellular lumen of fungal cells and how this can be improved. Here, we addressed both questions by applying two different polymeric particles for delivery of compounds. Their formulation was based on two biocompatible polymers, i.e., poly(lactic-co-glycolic acid)50:50 and poly(methyl methacrylate-stat-methacrylic acid)90:10 yielding particles with hydrodynamic diameters ranging from 100 to 300 nm. The polymers were covalently labeled with the fluorescent dye DY-550 to monitor the interaction between particles and fungi by confocal laser scanning microscopy. Furthermore, the fluorescent dye coumarin-6 and the antifungal drug itraconazole were successfully encapsulated in particles to study the fate of both the cargo and the particle when interacting with the clinically most important human-pathogenic fungi Aspergillus fumigatus, A. terreus, Candida albicans, and Cryptococcus neoformans. While the polymers were exclusively located on the fungal surface, the encapsulated cargo was efficiently transported into fungal hyphae, indicated by increased intracellular fluorescence signals due to coumarin-6. In accordance with this finding, compared to the pristine drug a reduced minimal inhibitory concentration for itraconazole was determined, when it was encapsulated. Together, the herein used polymeric particles were not internalized by pathogenic fungi but were able to efficiently deliver hydrophobic cargos into fungal cells.

Miniemulsion polymerization at low temperature: A strategy for one-pot encapsulation of hydrophobic anti-inflammatory drugs into polyester-containing nanoparticles.

HYPOTHESIS: Conventional synthesis methods of polymeric nanoparticles as drug delivery systems are based on the use of large amounts of organic solvents, hence requiring several steps for the obtaining of waterborne dispersions. In view of the need for new environmentally friendly methods, emulsion polymerization and their related techniques are a good alternative for the production of monodispersed waterborne dispersions of biodegradable nanoparticles in a cleaner, reproducible and faster manner. EXPERIMENTS: Herein, the miniemulsion polymerization technique at low temperature using poly(2-ethyl-2-oxazoline) as surfactant has been developed for poly(hydroxyethyl methacrylate-lactic acid) and poly(hydroxyethyl methacrylate-lactic-co-glycolic acid) nanoparticles. Additionally, the anti-inflammatory drug BRP-187 was used to proof the potential of this technique in the encapsulation of hydrophobic drugs. The effect of the oligomer composition on the miniemulsion and the final dispersion stability, the final oligomer conversion, the polymer particle size and the drug encapsulation efficiency has been studied. FINDINGS: Monodisperse spherical particles ranging between 170 and 250 nm in diameter in long term non-toxic stable waterborne dispersions were obtained with drug encapsulation efficiencies up to 66%. In contrast with conventional synthesis techniques, residual organic solvents are completely removed and, thus, the potential of redox initiated miniemulsion polymerization to obtain stable drug loaded poly(hydroxyethyl methacrylate-lactic acid) and poly(hydroxyethyl methacrylate-lactic-co-glycolic acid) nanoparticles in an efficient and fast manner is shown.

PLA/PLGA-Based Drug Delivery Systems Produced with Supercritical CO2-A Green Future for Particle Formulation?

Supercritical carbon dioxide (SC-CO2) can serve as solvent, anti-solvent and solute, among others, in the field of drug delivery applications, e.g., for the formulation of polymeric nanocarriers in combination with different drug molecules. With its tunable properties above critical pressure and temperature, SC-CO2 offers control of the particle size, the particle morphology, and their drug loading. Moreover, the SC-CO2-based techniques overcome the limitations of conventional formulation techniques e.g., post purification steps. One of the widely used polymers for drug delivery systems with excellent mechanical (Tg, crystallinity) and chemical properties (controlled drug release, biodegradability) is poly (lactic acid) (PLA), which is used either as a homopolymer or as a copolymer, such as poly(lactic-co-glycolic) acid (PLGA). Over the last 30 years, extensive research has been conducted to exploit SC-CO2-based processes for the formulation of PLA carriers. This review provides an overview of these research studies, including a brief description of the SC-CO2 processes that are widely exploited for the production of PLA and PLGA-based drug-loaded particles. Finally, recent work shows progress in the development of SC-CO2 techniques for particulate drug delivery systems is discussed in detail. Additionally, future perspectives and limitations of SC-CO2-based techniques in industrial applications are examined.

Co-encapsulation of CdSe/ZnS and CeO2 nanoparticles in waterborne polymer dispersions: enhancement of fluorescence emission under sunlight.

Hybrid core/shell polymer particles with co-encapsulated quantum dots (QDs) (CdSe/ZnS) and CeO2 nanoparticles have been synthesized in a two stage semi-batch emulsion polymerization process. In the first stage, both inorganic nanoparticles are incorporated into cross-linked polystyrene (PS) particles by miniemulsion polymerization. This hybrid dispersion is then used as the seed to produce the core/shell particles by starved feeding of methyl methacrylate and divinylbenzene (MMA/DVB) monomers. The core/shell hybrid dispersions maintained in the dark exhibit stable fluorescence emission over time, and notably their fluorescence intensity increases under sunlight, likely due to the effect of the co-encapsulated CeO2 nanoparticles that change the optical properties of the environment of the quantum dot particles. The fluorescence increase depends on the QD : CeO2 ratio, with the 1 : 2 ratio resulting in the highest increase (280%). Furthermore, a film forming hybrid latex has been synthesized using the former core/shell PS/QD/CeO2/PMMA particles as seeds and feeding under semi-batch conditions methyl methacrylate, butyl acrylate and acrylic acid. Films cast from this core/shell/shell hybrid dispersion also exhibit fluorescence, and as for the core/shell latex the fluorescence increases under sunlight exposure. Interestingly, the increase in the film is at least two times higher than that in the latex, which is attributed to the additional effect of the neighboring coalesced particles containing CeO2 affecting the environment of the QDs.