title: PEO-PPO-PEO/Poly(DL-lactide-co-caprolactone) Nanoparticles as Carriers for SN-38: Design, Optimization and Nano-Bio Interface Interactions.
abstract: Encapsulation of extremely hydrophobic substances such as SN-38 into nanoparticles, is a promising approach to solve the solubility issue and enable drug administration. Moreover, nanocarriers' tumor homing behavior, targeted and controlled release at the site of action will optimize therapeutic potency and decrease toxicity of the incorporated drug substance. However, the enormous drug hydrophobicity might limit the capacity for encapsulation as the premature drug precipitation will contribute to fast free drug crystal growth, low drug incorporation and huge waste of the active material. In this article we defined the optimal region for manufacturing of SN-38 loaded PEO-PPO-PEO/P(DL)LCL nanoparticles (NPs) with high efficacy of encapsulation, suitable particle size and different surface properties, using D-optimal design and nanoprecipitation as production method. Further we made an approach to investigate the interactions with macromolecules at the nano-bio interface which are predetermined by the physico-chemical and surface properties of the NPs, and are important determinants for the biological identity of the nanoparticles, the potential for evasion of the physiological barriers and the efficacy of localization at the site of action. Here we present in depth analysis of the behavior of two types of nanoparticles with different surface properties through structured protein interaction and bioreactivity experiments in order to presuppose NP performance and toxicological profile in biological environment.
authors.forename: Rozafa
authors.initials: R
authors.lastname: Koliqi
authors.forename: Simona
authors.initials: S
authors.lastname: Dimchevska
authors.forename: Nikola
authors.initials: N
authors.lastname: Geskovski
authors.forename: Gjorgji
authors.initials: G
authors.lastname: Petruševski
authors.forename: Marina
authors.initials: M
authors.lastname: Chacorovska
authors.forename: Biljana
authors.initials: B
authors.lastname: Pejova
authors.forename: Delyan R
authors.initials: DR
authors.lastname: Hristov
authors.forename: Sonja
authors.initials: S
authors.lastname: Ugarkovic
authors.affiliation: Institute of Pharmaceutical Technology, Faculty of Pharmacy, University Ss. Cyril and Methodius, Skopje, Republic of Macedonia. kago@ff.ukim.edu.mk.
authors.forename: Katerina
authors.initials: K
authors.lastname: Goracinova
mesh_terms: D000327:Adsorption; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D000077146:Irinotecan; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011409:Propylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012995:Solubility
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; C116176:PEO-PPO-PEO; D011091:Polyesters; D011409:Propylene Glycols; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; C062968:lactide-caprolactone copolymer; D000077146:Irinotecan; D002166:Camptothecin