Bioerodible Polymeric Nanoparticles for Targeted Delivery of Proteic Drugs

Abstract

Significant efforts are being devoted to develop nanotechnology for drug delivery, mainly because of the distinct advantages offered by nanometer-size polymeric systems. Moreover, targeted drug delivery can be obtained by polymer conjugation to biospecific ligands. The present investigation was aimed mainly at determining the targeting ability of hybrid nanoparticles based on synthetic polymer/protein hybrid matrices. These nanoparticles were designed for liver targeted release of proteic drugs with antiviral activity, such as alpha-interferon. Human serum albumin and the monoesters of alternating copolymers of maleic anhydride/alkyl vinyl ethers of oligo(ethylene glycol) were selected as proteic and synthetic components, respectively. Digalactosyl diacyl glycerol, a natural glycolipid selectively recognized by the asialofetuin receptor present on liver hepatocytes was used as active targeting agent. Nanoparticles of 100-300 nm average size were obtained by controlled coprecipitation method. Investigation of nanoparticle surface properties by spectroscopic analysis and by biological tests indicated that the synthesized nanoparticles do expose on their surface targeting moieties that selectively interact with liver hepatocytes receptors.

Targeted Delivery of Protein Drugs by Nanocarriers

“…Albumin can also be used in combination with synthetic polymers; hybrid nanoparticles composed of human serum albumin (HSA) and hemiesters of alternating copolymers of maleic anhydride/alkyl vinyl ethers of oligo(ethylene glycol) were prepared and made able to target liver hepatocytes thanks to digalactosyl diacyl glycerol (Figure 5), a natural glycolipid selectively recognized by the asialofetuin receptor [177,178]. The aforementioned alternating copolymers were also used for the formulation of bioerodible polymer matrices in conjunction with HSA and stabilized with β-cyclodextrins, providing good in vitro and in vivo biocompatibility [179].…”

“…SEM micrograph of nanoparticles obtained by co-precipitation of the n -butyl hemiester of the alternating copolymer of maleic anhydride/tetraethylene glycol vinyl ether and HSA and coated with digalactosyl diacyl glycerol as targeting moiety (bar is 1 μm) [178]. …”

Micro/Nanostructured Polymeric Systems for Biomedical and Pharmaceutical Applications

“…This methodology does not entail the use of chlorinated solvents and vigorous shear mixing, therefore, the biological activity of the loaded drugs, typically proteins, is preserved [119][120][121]. Albumin, α-interferon, trypsin, urokinase and hemoglobin have been loaded into bioerodible polymeric nanoparticles by applying the described technique (Figure 9) [122][123][124][125][126].…”

Targeted delivery of proteins by nanosized carriers

“…In addition, the folate receptor is efficiently internalized within the cell after binding with its ligand (folic acid). 69 Other authors took a similar approach, by using sugars 54,70 and glycolipids 57,71 whose receptors are expressed only by specific cell types. It must be stressed that interactions with blood components also affect the organ distribution of colloidal drug carriers.…”

“…These include gelatin, 43,60,84,85 albumin, 43,86 blends of human serum albumin, and the butyl hemiester of the alternating copolymer of maleic anhydride and 2-methoxyethyl vinyl ether, 57,71 albumin-poly(L-lactic acid) (PLA) blends, 25,29 PLA, 55,87 PEG-PLA block copolymers, 29,30,44 sugarterminated PEG-PLA block copolymers, 70 blends of maleimide-PEG-PLA and methoxy-PEG-PLA copolymers, 88 poly(D,L-lactic-co-glycolic acid) surface coated with poly(L-lysine)-poly(ethylene glycol)-folate (PLL-PEG-FOL) conjugate, 49 poloxamer-coated PLA, 27 poly(butyl cyanoacrylate), 85 polysorbate 80-coated poly(butyl cyanoacrylate), 87 Tween 75-coated poly(butyl cyanoacrylate), 40 poly(hexadecyl cyanoacrylate), 48 poly(methoxyPEG cyanoacrylate-co-hexadecyl cyanoacrylate), 48 poly(N-(terbutyloxycarbonyl)aminopoly(ethylene glycol) cyanoacrylate-co-hexadecyl cyanoacrylate), 48 crosslinked poly(N-vinyl-2-pyrrolidinone), 89 peptide building blocks, 50 polystyrene, 54 polyphosphoesters. 90 …”