Biodegradable nanoparticles for drug and gene delivery to cells and tissue

Polylactic acid is proving to be a viable alternative to petrochemical-based plastics for many applications It is produced from renewable resources and is biodegradable, decomposing to give H2O, CO2, and humus, the black material in soil In addition, it has unique physical properties that make it useful in diverse applications including paper coating, fibers, films, and packaging (see Figure)

Polylactic Acid Technology

Many types of nanoparticles (NPs) are tested for use in medical products, particularly in imaging and gene and drug delivery. For these applications, cellular uptake is usually a prerequisite and is governed in addition to size by surface characteristics such as hydrophobicity and charge. Although positive charge appears to improve the efficacy of imaging, gene transfer, and drug delivery, a higher cytotoxicity of such constructs has been reported. This review summarizes findings on the role of surface charge on cytotoxicity in general, action on specific cellular targets, modes of toxic action, cellular uptake, and intracellular localization of NPs. Effects of serum and intercell type differences are addressed. Cationic NPs cause more pronounced disruption of plasma-membrane integrity, stronger mitochondrial and lysosomal damage, and a higher number of autophagosomes than anionic NPs. In general, nonphagocytic cells ingest cationic NPs to a higher extent, but charge density and hydrophobicity are equally important; phagocytic cells preferentially take up anionic NPs. Cells do not use different uptake routes for cationic and anionic NPs, but high uptake rates are usually linked to greater biological effects. The different uptake preferences of phagocytic and nonphagocytic cells for cationic and anionic NPs may influence the efficacy and selectivity of NPs for drug delivery and imaging.

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The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles.

1: Magnetic Particles: Preparation, Properties and Applications: M. Ozaki. 2: Maghemite (gamma-Fe2O3): A Versatile Magnetic Colloidal Material C.J. Serna, M.P. Morales. 3: Dynamics of Adsorption and Oxidation of Organic Molecules on Illuminated Titanium Dioxide Particles Immersed in Water M.A. Blesa, R.J. Candal, S.A. Bilmes. 4: Colloidal Aggregation in Two-Dimensions A. Moncho-Jorda, F. Martinez-Lopez, M.A. Cabrerizo-Vilchez, R. Hidalgo Alvarez, M. Quesada-PMerez. 5: Kinetics of Particle and Protein Adsorption Z. Adamczyk.

Surface and Colloid Science

Temperature-sensitive aqueous microgels.

Temperature- and ionic strength-induced conformational changes in the lipid head group region of liposomes as suggested by zeta potential data.

In recent years, the use of polylactide (PLA), a synthetic biodegradable polymer, as drug-loaded matrix has been examined in the hope that the matrix will decay and decompose after releasing the drug in a sustained manner over a long period of time in the human body[1–8]. However, no detailed work has been done on the degradation rate of PLA even under in vitro conditions. The present paper deals with the rate of in vitro degradation of PLA microcapsules in various environmental conditions.

Preparation and in vitro degradation properties of polylactide microcapsules.

Phagocytic uptake of polystyrene microspheres by alveolar macrophages: effects of the size and surface properties of the microspheres

The electrophoretic mobility and the size of two types of model latex particles with a core-shell structure were measured and compared with those for latex particles with no shell structure. These latex particles have a negatively charged core, covered with negatively charged or uncharged temperature-sensitive poly ( N -isopropylacrylamide) hydrogel layers. The charge density and the "softness" of the latex surface layer were obtained from the electrophoretic mobility data of the latex particles, showing a sudden change around the phase transition temperature (33°C) of poly( N -isopropylacrylamide). Also, these changes are correlated with a change in the size of the latex particles around 33°C. The temperature dependence of the hydrogel layer thickness on the particle accounts for the above observations. The negatively charged poly( N -isopropylacrylamide) surface gel layer shrinks as temperature increases, leading to an accumulation of the poly( N -isopropylacrylamide) segments on the particle core. This makes the particle harder. The uncharged poly( N -isopropylacrylamide) surface gel layer, on the other hand, does not change its thickness appreciably, but a change in configuration of the polymer segments occurs as the temperature increases, so that the surface layer becomes softer, probably because void spaces are created in the surface layer by the accumulation of polymer segments.

Surface Structure of Latex Particles Covered with Temperature-Sensitive Hydrogel Layers

The hydrolytic degradation rate of poly(L-lactide) molecules constituting the microcapsule membrane was estimated at different pH, ionic strength and buffer concentration. Poly(L-lactide) microcaps...

Kimiko Makino

Papers

Temperature- and ionic strength-induced conformational changes in the lipid head group region of liposomes as suggested by zeta potential data.

Preparation and in vitro degradation properties of polylactide microcapsules.

Phagocytic uptake of polystyrene microspheres by alveolar macrophages: effects of the size and surface properties of the microspheres

Surface Structure of Latex Particles Covered with Temperature-Sensitive Hydrogel Layers

Mechanism of hydrolytic degradation of poly(L-lactide) microcapsules: effects of pH, ionic strength and buffer concentration.