ABSTRACT
A series of diblock copolymers were synthesized by ring-opening polymerization of l- or d-lactide in the presence of monomethoxy poly(ethylene glycol) (mPEG) with molar masses of 2000 and 5000. The aggregation behavior of the resulting water soluble PLA/PEG diblock copolymers in aqueous medium was studied with dynamic and static light scattering (DLS and SLS), in combination with aqueous gel permeation chromatography (GPC). The average hydrodynamic radius (R(h)) of l-PLA/PEG and d-PLA/PEG mixed micelles is lower than that of l-PLA/PEG single micelles due to the stereocomplexation effect between l-PLA and d-PLA blocks. It is also confirmed that the micelle size increases with increasing temperature and hydrophobic block length, but decreases after salt addition. Aqueous GPC and SLS were used to evaluate the molecular weight (M(w)) and aggregation number (N(agg)) of the micelles. Mixed micelles present lower N(agg) than single copolymer micelles due to stereocomplexation. N(agg) decreases with increasing hydrophobic block length, and decreases upon addition of NaCl, in agreement with a more compact structure. In contrast, N(agg) increases with elevating temperature. The average radius of gyration (R(g)) and R(g)/R(h) ratio data show that both increase with increasing temperature, suggesting that micelles exhibit a compact hard-sphere structure at 15 degrees C and a swollen structure at 35 degrees C. As the temperature increases from 15 degrees C to 35 degrees C, the second virial coefficient (A(2)) of PLA/PEG copolymers turns from negative to positive, which means that water changes from poor solvent to good solvent. The fact that the average density (rho) of PLA/PEG micelles decreases with increasing temperature confirms that micelles exhibit a looser structure at higher temperatures due to water swelling effect. The higher rho value of mixed micelles as compared to single micelles also confirms a more compact structure of the former. In addition, due to the much higher N(agg) and lower R(h), PLA/PEG2000 micelles present higher rho value than PLA/PEG5000 ones.
Subject(s)
Drug Carriers/chemistry , Drug Delivery Systems , Polyesters/chemistry , Polyethylene Glycols/chemistry , Chromatography, Gel/methods , Hydrophobic and Hydrophilic Interactions , Light , Micelles , Molecular Weight , Scattering, Radiation , Solvents/chemistry , Temperature , Water/chemistryABSTRACT
The adsorption of proteinase K on PLLA and PDLA films was studied by CA, surface tension, and microscopic measurements. ESEM clearly shows that proteinase K can irreversibly adsorb on PLLA film. In contrast, no enzyme adsorption was detected on PDLA film under the same conditions. The CA of PLLA film rapidly decreases after immersion in Tris buffer containing proteinase K, whereas that of PDLA remains unchanged. These findings indicate that enzyme adsorption may be a prerequisite for enzymatic degradation of polylactide substrates. Surface tension measurements allow calculation of the average area occupied per proteinase K molecule. The results show that the enzyme molecules exhibit a more compact conformation at higher temperature.
Subject(s)
Endopeptidase K/metabolism , Polyesters/metabolism , Adsorption , Chromatography, Gel , Microscopy, Electron, Scanning , Polyesters/chemical synthesis , Surface Tension , X-Ray DiffractionABSTRACT
Copolymers of polylactide (PLA) and poly(ethylene glycol) (PEG) were synthesized by ring-opening polymerization of L- or D-lactide in the presence of mono- or dihydroxyl PEG using nontoxic zinc lactate as catalyst. The resulting diblock and triblock copolymers were characterized by various analytical techniques such as SEC, (1)H NMR, XRD, and DSC. Bioresorbable micelles were prepared from aqueous solutions of the various copolymers without using any organic solvent. The mixed micellar solutions containing both L-PLA/PEG and D-PLA/PEG copolymers appeared more stable than the separate solutions according to critical micellar concentration (CMC) results, which could be assigned to stronger interactions between L-PLA and D-PLA blocks. The properties of the polymeric micelles strongly depend on the chain structure and composition of the copolymers. CMC values in the presence of salt and at 37 degrees C suggested that the micelles could exhibit good stability in vivo. Thermodynamic parameters calculated from the dependence of CMC on temperature indicate that the micellization process is spontaneous and driven by entropy gain. Dynamic light scattering (DLS) measurements showed one or two populations of micelles for dilute and concentrated solutions, the micelle size decreasing upon dilution. TEM confirmed the presence of micelles, but the size estimated from TEM was smaller than that from DLS due to the dehydration and shrinkage during drying.
