The entry of drug payloads into the circulatory system is met by rapid removal by resident macrophages. The almost immediate drop in circulating levels of the therapeutic agent has been identified as a major obstacle for efficient drug delivery. Various physical properties determine the fate of NP-based (NP= nanoparticle) drug-delivery platforms in vivo. Size, surface charge, and surface hydrophobicity of the particles all affect the ability of macrophages to remove them from circulation and, hence, their bioavailability. Large particles (> 200 nm diameter) are more easily captured by macrophages. Ultrafine nanoparticles can avoid resident macrophage capture and are thus more likely to be eventually removed from the body by renal clearance, thereby decreasing the potential for bioaccumulation. The use of ultrafine materials of appropriate size and composition for the delivery of potent and effective therapeutics may mitigate some of the problems associated with drug delivery to the central nervous system (CNS) as well as management of other diseases. Ultrafine polyacrylamide-based hydrogels are an example of the many interesting materials used for drug delivery in vivo. The neutral surface properties of the hydrophilic polyacrylamide-based nanoplatforms reduce uptake by macrophage and make them a candidate for development as a useful therapeutic entity. Lower protein adsorption and high water content further decrease the opsonization by plasma proteins in the bloodstream and aid in the evasion of circulating and tissue-based macrophages. The size of polyacrylamide-based nanoparticles can be easily modulated by synthetic approaches. Furthermore, polyacrylamide can easily copolymerize with other monomers to introduce functional groups; thus, targeting tags can be incorporated to guide drug delivery. All this suggests that polyacrylamide-based hydrogels may be used as a novel class of safe nanosized drug carriers for the in vivo delivery of a variety of therapeutic moieties. Photodynamic therapy (PDT), a promising new treatment for certain types of cancer, has received considerable attention in recent years. The principle of PDT is that optically excited photosensitizer molecules, localized in cancer tissues, transfer their energy to molecular oxygen to form highly reactive singlet oxygen (O2), which kills living cells. The subcellular localization of photosensitizers depends on the photosensitizer3s nature and the cell lines studied. Among the “second-generation” photosensitizers, meta-tetra(hydroxyphenyl)chlorin (mTHPC) has recently received extensive attention because of its high phototoxicity at very low concentrations, or low light levels, and it has recently been approved in the European Union for head and neck cancer therapy. However, a specific formulation is required to deliver the hydrophobic drug. This is because the injectable mTHPC, for PDT clinical trials and for most in vivo studies reported in the literature, still uses the standard solution (ethanol/PEG400/water) formulation. In this way, after administration, the hydrophobic molecules are diluted in the biological environment. Eventually the mTHPC molecules precipitate out and stick onto cell or tissue surfaces, causing side effects. Although a few reports show the encapsulation of mTHPC into sub-200-nm silica or poly(lactic-co-glycolic acid) (PLGA) nanoparticles, size and surface issues, as well as application in a biological environment, remain open. Herein, a novel synthetic approach is described for obtaining ultrafine hydrophilic polyacrylamide-based nanoparticles. Used as an example, mTHPC-encapsulating nanoparticles are synthesized. The behaviors of the drug molecule, within nanoparticles and in solution, are chemically compared for their phototoxicity. Finally, their effectiveness in killing living cells was evaluated. It is well-known that for inverse microemulsions the droplet size is determined by the molar ratio of water to surfactant, [W0]/[surfactant]. [7] Also, droplet stability during polymerization depends on the volume of the water droplets. The volume reduction of the water pool and the increase in surfactant, in the inverse microemulsion, makes the droplet more rigid and thus decreases the possibility of droplet collisions during polymerization. Thus, small-size nanoparticles can be obtained. Experiments have shown that by changing the molar ratio of water to surfactants one could control both size and shape of the nanoparticles. We chose to emulsify both the monomers and cross-linkers directly into hexane, without water, to get the smallest polyacrylamide nanoparticles. First, the ultrafine blank polyacrylamide particles were synthesized. Acrylamide (AAm) monomer and cross-linker N,N-methylenebis(acrylamide) (MBA) were suspended in a hexane solution containing surfactant (AOT= [*] Dr. D. Gao, Prof. R. Kopelman Department of Chemistry University of Michigan Ann Arbor, MI 48109-1055 (USA) Fax: (+1)734-936-2778 E-mail: kopelman@umich.edu
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Jul 31, 2024
Zhiru Yang + 16
Open Access