A new double emulsion solvent diffusion technique for encapsulating hydrophilic molecules in PLGA nanoparticles.
The commonly utilized techniques for encapsulating hydrophilic molecules in NP suffer from low encapsulation efficiency because of the drug rapid partitioning to the external aqueous phase. We hypothesized that combining the double emulsion system with a partially water-soluble organic solvent, could result in better encapsulation yield of hydrophilic molecules in nano-sized NP, and the utilization of both biocompatible surfactants and solvents. As a model drug we used alendronate, a hydrophilic low MW bisphosphonate. The new NP preparation technique, double emulsion solvent diffusion (DES-D), resulted in improved formulation characteristics including smaller size, lower size distribution, higher encapsulation yield, and more biocompatible ingredients in comparison to classical methods. The utilization of partially water-miscible organic solvent (ethyl acetate) enabled rapid diffusion through the aqueous phase forming smaller NP. In addition, the formulated alendronate NP exhibited profound inhibition of raw 264 macrophages, depletion of rabbit's circulating monocytes, and inhibition of restenosis in the rat model. It is concluded that the new technique is advantageous in terms of smaller size, lower size distribution, higher encapsulation yield, and more biocompatible ingredients, with unaltered bioactivity.
Department of Pharmaceutics, Faculty of Medicine, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
Einat
E
Cohen-Sela
Michael
M
Chorny
Nickolay
N
Koroukhov
Haim D
HD
Danenberg
Gershon
G
Golomb
D000085:Acetates / Q000737:chemistry; D019386:Alendronate / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D001682:Biological Availability; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016893:Carotid Stenosis / Q000473:pathology / Q000517:prevention & control / Q000601:surgery; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004655:Emulsions / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D051381:Rats; D055502:Secondary Prevention; D013010:Sonication; D013501:Surface-Active Agents / Q000737:chemistry
D000085:Acetates; D050071:Bone Density Conservation Agents; D004337:Drug Carriers; D004655:Emulsions; D013501:Surface-Active Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C007650:ethyl acetate; D019386:Alendronate