Polylactide containing nanoparticles - new carriers of active compounds

摘要

Two amphiphilic block copolymers poly(L-lactide)-b-polyglyci-dol-b-poly(ethylene oxide) (PLA-b-PGly-b-PEOX) were synthesized:PLA-b--PGly-b-PEOX(I) with M_n equal 6260 (PLA),510 (PGly) and 6600 (PEOX) and PLA-b-PGly-b-PEOX(II) with M_n equal 3600 (PLA),500 (PGly) and 5500 (PEOX).Polyglycidol segment in PLA-b-PGly-b-PEOX(II) was modified in reaction with succinic anhydride - the reaction leading to conversion of -CH_2OH groups of polyglycidol monomeric units to -CH_2OC(O)CH_2CH_2COOH moieties with carboxyl groups [modified PLA-b-PGly-b-PEOX(II) was denoted as PLA-b-PGly-b-PEOX(IIc)].Molecules of all three copolymers did self assemble in water into polymeric nanoparticles with number average diameters equal 20.010.8 nm [PLA-b-PGly-b-PEOX(I)],20.9+-0.3 nm [PLA-b-PGly-b-PEOX(II)] and 33+-1 nm [PLA-b-PGly-b--PEOX(IIc)].Critical aggregation concentration (CAC - a concentration above which nanoparticles are formed) was equal 1.55centre dot10~(-2),7.0centre dot10~(-2) and 2.51centre dot10~(-1) g/L for PLA-b-PGly-b-PEOX(I),and PLA-b-PGly-b-PEOX(IIc),respectively.Nanoparticles were formed also in presence of pyrene and partition of pyrene between solution and nanoparticles was determined.For example,for concentrations of PLA-b-PGly-b-PEOX(II) and pyrene equal 1.95centre dot10~(-3) g/L and 4.94 centre dot 10~(-7) g/L the fraction of encapsulated pyrene was ca.10 % whereas for the same concentration of pyrene but for higher concentration of PLA-b-PGly--b-PEOX(II),above 2.50centre dot10~(-1) g/L,the whole amount of pyrene was incorporated into nanoparticles.Profile of pyrene release from nanoparticles was bi-exponential with the rate constant for "fast" (k_f) component equal 9.5centre dot10~(-2),3.8centre dot10~(-2) and 1.5centre dot10~(-1) L/h,for PLA-b-PGly-b-PEOX(I),PLA-b-PGly--b-PEOX(II) and PLA-b-PGly-b-PEOX(IIc),respectively,and with the rate constant for "slow" (k_s) component essentially the same for nanoparticles from all terpolymers equal (8.4+-0.2)centre dot10~(-3) L/h.It has been suggested that "fast" rate describes the release of pyrene from shells of nanoparticles whereas the "slow" one describes the release from their cores.