Serum-stable, long-circulating paclitaxel-loaded colloidal carriers decorated with a new amphiphilic PEG derivative.
The paper describes sterically stabilized lipid nanocapsules (LNC) and multilamellar liposomes (MLV) coated using a new amphiphilic conjugate of PEG(2000) with a 2-alkyl-lipoamino acid (LAA). A complement activation assay (CH50) and uptake experiments by THP-1 macrophage cells were used to assess in vitro the effectiveness of the PEG-LAA derivative of modifying the surface behavior of nanocarriers. Administered to rats or Swiss mice, respectively, the PEG(2000)-LAA-modified LNC and MLV showed plasma half-lives longer than the corresponding naked carriers. To assess the ability of nanocarriers to specifically reach tumor sites, paclitaxel (PTX)-loaded LNC and MLV were administered subcutaneously to rats implanted with a 9L glioma. Animals treated with saline or naked LNC and MLV underwent a quick expansion of tumor mass, up to a volume of 2000 mm(3) 25 days after the injection of tumor cells. On the contrary, treatment with a PEG-LAA modified LNC carrier reduced the growth of the tumor volume, which did not exceed 1000 mm(3) by day 25. Analogous positive results were obtained with the liposomal systems. The experimental findings confirmed that these new PEG-LAA conjugates allow to obtain sterically stable nanocarriers that behave effectively and in a comparable or even better way than the (phospho)lipid PEG derivatives commercially available.
Department of Drug Sciences, University of Catania, viale A. Doria, 6, I-95125 Catania, Italy; Etnalead s.r.l., c/o Etna Building -Scuola Superiore di Catania, via S. Nullo, 5/i, I-95124 Catania, Italy.
Livia
L
Basile
Inserm U 1066 MINT "Micro et nanomedicines Biomimétiques", IBS-CHU, 4 rue Larrey, F-49933 Angers cedex 9, France; LUNAM Université, Université d'Angers, France. Electronic address: catherine.passirani@univ-angers.fr.
Catherine
C
Passirani
Inserm U 1066 MINT "Micro et nanomedicines Biomimétiques", IBS-CHU, 4 rue Larrey, F-49933 Angers cedex 9, France; LUNAM Université, Université d'Angers, France.
Ngoc-Trinh
NT
Huynh
Inserm U 1066 MINT "Micro et nanomedicines Biomimétiques", IBS-CHU, 4 rue Larrey, F-49933 Angers cedex 9, France; LUNAM Université, Université d'Angers, France.
Jérôme
J
Béjaud
Inserm U 1066 MINT "Micro et nanomedicines Biomimétiques", IBS-CHU, 4 rue Larrey, F-49933 Angers cedex 9, France; LUNAM Université, Université d'Angers, France.
Jean-Pierre
JP
Benoit
Department of Drug Sciences, University of Catania, viale A. Doria, 6, I-95125 Catania, Italy.
Giovanni
G
Puglisi
Department of Drug Sciences, University of Catania, viale A. Doria, 6, I-95125 Catania, Italy. Electronic address: r.pignatello@unict.it.
Rosario
R
Pignatello
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003102:Colloids; D015941:Complement Hemolytic Activity Assay; D004337:Drug Carriers; D004339:Drug Compounding; D018316:Gliosarcoma / Q000378:metabolism / Q000473:pathology; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008081:Liposomes; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D053769:Nanocapsules; D036103:Nanotechnology; D017239:Paclitaxel / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry*; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D013499:Surface Properties; D013501:Surface-Active Agents / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D047368:Tumor Burden / Q000187:drug effects
D000972:Antineoplastic Agents, Phytogenic; D003102:Colloids; D004337:Drug Carriers; D008081:Liposomes; D053769:Nanocapsules; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; D017239:Paclitaxel