Nanoparticle Drug Delivery
“The use of nanotechnology in medicine and more specifically drug delivery is set to spread rapidly. Currently many substances are under investigation for drug delivery and more specifically for cancer therapy. Interestingly pharmaceutical sciences are using nanoparticles to reduce toxicity and side effects of drugs and up to recently did not realize that carrier systems themselves may impose risks to the patient. The kind of hazards that are introduced by using nanoparticles for drug delivery are beyond that posed by conventional hazards imposed by chemicals in classical delivery matrices. For nanoparticles the knowledge on particle toxicity as obtained in inhalation toxicity shows the way how to investigate the potential hazards of nanoparticles. The toxicology of particulate matter differs from toxicology of substances as the composing chemical(s) may or may not be soluble in biological matrices, thus influencing greatly the potential exposure of various internal organs. This may vary from a rather high local exposure in the lungs and a low or neglectable exposure for other organ systems after inhalation. However, absorbed species may also influence the potential toxicity of the inhaled particles. For nanoparticles the situation is different as their size opens the potential for crossing the various biological barriers within the body. From a positive viewpoint, especially the potential to cross the blood brain barrier may open new ways for drug delivery into the brain. In addition, the nanosize also allows for access into the cell and various cellular compartments including the nucleus. A multitude of substances are currently under investigation for the preparation of nanoparticles for drug delivery, varying from biological substances like albumin, gelatine and phospholipids for liposomes, and more substances of a chemical nature like various polymers and solid metal containing nanoparticles. It is obvious that the potential interaction with tissues and cells, and the potential toxicity, greatly depends on the actual composition of the nanoparticle formulation.”
“Besides the potential beneficial use also attention is drawn to the questions how we should proceed with the safety evaluation of the nanoparticle formulations for drug delivery. For such testing the lessons learned from particle toxicity as applied in inhalation toxicology may be of use. Although for pharmaceutical use the current requirements seem to be adequate to detect most of the adverse effects of nanoparticle formulations, it can not be expected that all aspects of nanoparticle toxicology will be detected. So, probably additional more specific testing would be needed.”
[De Jong and Borm, International Journal of Nanomedicine, #3, 133-149 (2008)
Recent Journal Articles
Paclitaxel-Loaded Polymer Nanoparticles for the Reversal of Multidrug Resistance in Breast Cancer Cells
(4211–4218) Advanced Functional Materials 21 #22 (2011)
Lee et al, South Korea and Germany,developed paclitaxel-loaded polymer nanoparticles for circumventing multidrug resistance (MDR) of malignant cancerous diseases, which is an unsolved clinical problem in cancer chemotherapy. By encapsulating paclitaxel in a water-soluble and biocompatible synthetic polyampholyte using a solid-state reaction the highly water-soluble paclitaxel-loaded nanoparticles are formed. The resulting paclitaxel nanoparticles with an average diameter of 250 nm show a significant reversal of chemoresistance in the drug-resistant variants (MCF7/ADR, MT3/ADR) by a factor of 100 or more. The novel paclitaxel nanoparticles enter MDR breast cancer cells by adsorptive endocytosis bypassing the P-gp, preventing the efflux of paclitaxel and thus restoring the anti-proliferative effect of paclitaxel. (RDC 11/16/2011)
In-Situ Incorporation of Amoxicillin in PVA/PVAc-co-PMMA Particles during Suspension Polymerizations
(34–40)Macromolecular Symposia 299-300 #1 (2011)
Oliveira et al of the Universidade Federal do Rio de Janeiro, Brazil used a suspension polymerization process to produce embolic particles with core-shell morphology. This technology was modified to allow for the in-situ incorporation of antibiotics (amoxicillin) in PVA/PVAc-co-PMMA core-shell particles. The incorporation of amoxicillin led to modification of some of the final polymer properties, including the particle morphology, the molecular weight distribution and the characteristic transition temperatures of the polymer material. Embolization is a radiological technique that consists in occluding a blood vessel intentionally with an embolic agent (particle). (RDC 2/25/2011)
Fabrication and characterization of porous poly(lactic-co-glycolic acid) (PLGA) microspheres for use as a drug delivery system
(2510-2517) Journal of Materials Science 46 #8 (2011)
Bao et al, South Korea fabricated Simvastatin (SIM) loaded porous poly(lactic-co-glycolic acid) (PLGA) microspheres using the W/O/W1/W2 double emulsion and solvent evaporation method. The optimal conditions for fabricating porous PLGA microspheres were determined to be 20% distilled water (v/v), 10% PLGA (m/v), and a 4:1 ratio of internal polyvinyl alcohol (PVA) to dichloromethane (DCM). The pores size distribution of porous PLGA microspheres was varied from 0.01 to 40 μm, while their particle displayed a bimodal size distribution that had two diameter peaks at around 100 μm and 500 μm. The SIM encapsulation efficacy was found to be very high with a yield near 80% and the porous PLGA microspheres showed the excellent biocompatibility. SIM loaded PLGA microspheres holds great promise for use in biomedical applications, especially in drug delivery system or tissue regeneration. (RDC 2/22/2011)
Tunable Amphiphilic Poly(Ether-Anhydride) Gel Nanoparticles for the Delivery of Hydrophobic Drugs
(167–178)Macromolecular Symposia 297 #1 (2010)
Wang, Cai and Guo of Tianjin University, China, prepared biodegradable amphiphilic poly(ether-anhydride) gel nanoparticles (GNPs) with a hydrophobic crosslinked core and a hydrophilic PEG shell from amphiphilic photo-crosslinkable ether-anhydride macromers via microemulsion photo-polymerization. The GNPs were used as the carriers to enhance the solubility of hydrophobic drugs. Indomethacin (IND) as a model drug was entrapped in the hydrophobic crosslinked core by an in situ embedding method. Results showed that IND maintained chemically intact during the formulation process, and its dissolution rate were improved compared to those of the pure IND. The GNPs prepared from PEG macromer (molecular weight: 4000) with the addition of MSA exhibited the zero-order release behavior, which is potentially useful to control the release of hydrophobic drugs. (RDC 2/25/2011)
2/4/2011
Interaction of antigen and antibody on core-shell polymeric microspheres
(267-273) Chinese Journal of Polymer Science 29, #2 (2011)
Li et al, China synthesized monodispersed microspheres with polystyrene as the core and poly(acrylamide-co-N-acryloxysuccinimide) as the shell by a two-step surfactant-free emulsion copolymerization. Rabbit immunoglobulin G (as antigen) was covalently coupled onto the microspheres by the reaction between succinimide-activated ester groups on the shell of the microspheres and amino groups of the antigen molecules. The size of particles was characterized by dynamic light scattering technique and was found to vary upon bioconjugation and interaction with proteins. The binding process was shown to be specific to goat anti-rabbit immunoglobulin G (as antibody) and reversible upon the addition of free antigen into the system. (RDC 2/12/2011)
Thermosensitive Poly(N-isopropylacrylamide)-g -Polyamidoamine Dendrimer Derivatives: Preparation and the Drug Release Behaviors
(158–166)Macromolecular Symposia 297 #1 (2010)
Wang et al of Tianjin University, China prepared a series of thermally responsive dendritic core-shell polymers based upon dendritic polyamidoamine (PAMAM), modified with carboxyl end-capped linear poly(N-isopropylacrylamide) (PNIPAAm-COOH) in different ratios via an esterification process. Indomethacin (IMC) as a model drug was loaded in the thermosensitive polymer-grafted dendrimer derivative and its release behavior was studied below and above its LCST (27°C vs 37°C). Results showed that the LCST of PNIPAAm-g-PAMAM was around 32°C compared with that of the pure PNIPAAm. The release behavior of the indomethacin entrapped in the internal cavities of the PNIPAAm-g-PAMAM showed that almost 77% of the drug was cumulatively released at 27°C after 10 hours, whereas only 20% was released at 37°C. The release rate of IMC from the IMC/PNIPAAm-g-PAMAM complex at 37C is significantly slower than that at 27C, which indicates that the PNIPAAm chains grafted on the surface of PAMAM dendrimer could act as a channel switching on-off button through expending or contracting in response to the temperature variation and could control the drug release by varying the surrounding temperature. (RDC 2/25/2011)
1/21/2011
Tunable Amphiphilic Poly(Ether-Anhydride) Gel Nanoparticles for the Delivery of Hydrophobic Drugs
(167–178)Macromolecular Symposia 297 #1 (2010)
Wang, Cai and Guo of the Tianjin University, China prepared biodegradable amphiphilic poly(ether-anhydride) gel nanoparticles (GNPs) with a hydrophobic crosslinked core and a hydrophilic PEG shell from amphiphilic photo-crosslinkable ether-anhydride macromers via microemulsion photo-polymerization. The particles were spherical in shape with a core-shell structure when maromers were added. The particles showed zero-order release behavior, which is potentially useful to control the release of hydrophobic drugs. (RDC 1/17/2011)