The solution properties of a N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer containing Zn(Ⅱ) 4,9,16,23-tetraaminophthalocyanine (HPMA-TAPC-Zn copolymer) attached to the copolymer via oligopeptide side chains (GFLGG) were studied using light scattering and spectroscopic methods. The light scattering data indicated that the copolymer formed aggregates in aqueous solutions stable down to c=2x10-5g/mL. The extent of aggregation decreased with increasing concentration of detergents in buffer solutions or organic solvents in mixed solvents as Tris buffer/DMSO. Dramatic changes in the aggregate formation were observed in the vicinity of a mixture composition of 60 vol% of DMSO. The local interactions of hydrophobic TAPC-Zn species were studied by absorption and fluorescence spectrometry. The majority of all TAPC-Zn species are dimerized in aqueous solutions by hydrophobic interactions and hydrogen bonds. The proportion of TAPC-Zn monomers and dimmers estimated for Tris buffer/DMSO mixtures from both the absorption and fluorescence spectra was correlated to the aggregation behavior of the copolymer. The copolymer aggregation was explained by the random association model. Mostly point-like contacts formed by TAPC-Zn dimers are supposed for aqueous solutions of HPMA-TAPC-Zn copolymer.

D, L-3-metbylglycolide (MG) was successfully polymerized with multifunctional initiator (trimethylolpropane (TMP) or pentaerythritol (PTOL)) and stannous octoate (SnOct2) catalyst in bulk at 110℃. The effects of molto ratios of monomer to initiator, monomer to catalyst and monomer conversion on the molecular weight of polymer were studiedi For the homopolymerization of MG with TMP initiator and SnOct2 catalyst, the molecular weight of polymer increases from 6840 to 35 010 with the molto ratio of monomer to initiator (45-450), and the molecular weight distribution is from 1.15 to 1.35. The results indicate that in the homopolymerization of MG, the molecular weight of polymer is proportional to the molar ratio of monomer to initiator and the monomer conversion. The molar ratio of monomer to catalyst has no influence on the molecular weight of polymer at least within the range of 500-4000. 1 H NMR spectra of the resulting polymers obtained from the homopolymerization of MG show that the homopolymerization of MG with TMP or PTOL initiator and SnOct2 catalyst produced two types of three arm or fore-arm star-sbaped polymers. The bulk ring-opening homopolymerization of MG proceeds through a "coordina tion-insertion" mechanism and follows the selective acyl-oxygen bond cleavage reaction, 13C NMR spectroscopy indicates that the obtained poly (D,L-lactic acid-co-glycolic acid) (50: 50, in molto-ratio; D,L-PLGA50) has an alternating structures of lactyl and glycolyl units.

Two types of three-arm or four-arm star-shaped hydroxy-terminated poly(ε-caprolactone) (PCL) were successfully synthesized via the ring-opening polymerization of ε-caprolactone (CL) with multifunctional initiator, such as trimethylolpropane (TMP) or pentaerythritol (PTOL), and stannous octoate (SnOct2) catalyst in bulk at 110℃. The number-average molecular weight of PCL is proportional to the molar ratio of monomer to initiator. 1H NMR spectroscopy of the resulting PCL indicates that it contains a primary hydroxy end group in each arm. The star-shaped PCL with hydroxy end groups can be used as a macroinitiator for block copolymerization with DL-3-methylglycolide (MG) using SnOct2 catalyst in bulk at 115℃. 1H NMR spectra of the resulting block copolymers show that the molecular weights and the unit compositions of the block copolymers were controlled by the molar ratios of MG monomer to hydroxy groups of PCL and MG to CL in feed, respectively. Moreover, the molecular weights of the resulting block copolymers linearly increased with the increase of the molar ratios of MG to CL in feed. The molecular weight distributions of the block copolymers were rather narrow (Mw/Mn) 1.09-1.26). 13C NMR spectra of the resulting block copolymers clearly show their diblock structures, that is, PCL as the first block and poly (DL-lactic acid-alt-glycolic acid) (DL-PLGA50) with alternating structures of lactyl and glycolyl units as the second block. Therefore, two types of three-arm or four-arm star-shaped diblock copolyesters comprising the first block PCL and the second block DL-PLGA50 were successfully synthesized via the sequential ring-opening polymerization of CL with multifunctional initiator and SnOct2 catalyst and then followed by copolymerization with MG.

Clotrimazole (CT)-containing proliposomes were prepared by penetrating an ethanol solution of CT and Egg phosphatidylcholine (PC) into microporous sorbitol particles, followed by vacuum evaporation of the solvent. As a result, CT proliposomes with free-flowing flowability were obtained. On contact with water, the proliposomes were rapidly converted into a liposomal dispersion, in which a certain amount of CT was entrapped by the liposomes. The result in scanning electronic micrograph confirmed the formation of liposomes structures from proliposomes, and the particles revealed round or ellipse. The ratio of drug to total lipid, ratio of PC to cholesterol and ratio of lipid to sorbitol affected the entrapment efficiency (EE%). The EE% of optimized formulation (CT 10mg, 0.1g total lipid, PC/CH ratio is 60∶40 and 1g sorbitol) in this investigation was 96.2±1.5%. The proliposomes system can provide sustaining release in simulated vaginal fluid at 37±1℃ for 24 h. In-vivo performance of blank proliposomes, a physical mixture of sorbitol and drug, clotrimazole proliposomes and commercial ointment formulation were evaluated using antifungal activity test. At 7 d post-dose, the c.f.u. of C. albicans decreased in proliposomes-treated groups than ointment and the physical mixture (t-Student, p＜0.05). The results indicated that CT-containing vaginal proliposomes prolonged drug release and may increase amount of drug retention into the mucosa to result in more antifungal efficacy. In addition, CT-proliposomes did not affect the morphology of vaginal tissues. Therefore, the dosage form might be further developed for safe, convenient, and effective treatment of vaginal candidasis with reduced dosing interval.