Pharmacokinetics and Tissue Distribution of Vinorelbine Bitartrate after Intraveous Administration of Liposomal and Injectable Formulations

A hydrophilic and temperature-induced degradation drug, vinorelbine bitartrate (VB)-loaded phosphatidylethanolamin liposomes (PSLs), was prepared by the thin-film hydration method. Liposomes were made of phosphatidylethanolamine: cholesteryl: oleic acid (PE: CHOL: OA, 3:3:1 mass/mass). The mean particle size of the PSLs ranged from 293.06 nm. The transmission electron microscope (TEM) images displayed that the shape of the PSLs was multilamellar vesicles with smooth surface. The highest entrapment efficiency (EE) and drug loading capacity (DL) could reach up to 68.5% and 6.23%, respectively. The PSLs was evaluated by comparing the rate of release of encapsulated VB in different phosphate buffer solution (PBS), and the result showed that the rate of drug release in acid medium was faster than in pH 7.4. Pharmacokinetic characteristics in vivo and the tissue distribution in mice were investigated, which provided experimental and theoretical basis for utilizing liposomes in malignant tumor chemotherapy.     

Mechanistic study of hydrolytic erosion and drug release behaviour of PLGA nanoparticles: Influence of chitosan

The hydrolytic erosion of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (PLGA-NPs) was investigated in vitro. The changes in physical properties of the nanoparticles with time were evaluated by ultra high-pressure liquid chromatographic (UHPLC) analysis, particle size analysis and scanning electron microscopy (SEM). Mass reduction data demonstrated a triphasic erosion pattern for PLGA-NPs with nearly no mass loss (3.0%) up to a week, followed by a rapid mass loss (weeks 1-3, 61.4%), and further followed by slow mass loss (weeks 3-5, 19.8%). SEM revealed microcavitation on the surface of nanoparticles, which tended to increase with the erosion time and eventually particle fragmentation was evident at 5 weeks. A significant increase in particle size was observed at 4 weeks which can be attributed to particle aggregation, however, at about 5 weeks, the particle size decreased significantly owing to particle fragmentation. The hydrolytic erosion of PLGA-NPs was found to be specifically proton catalyzed. The release profile of the model drug, moxifloxacin, from PLGA-NPs was closely related to nanoparticle erosion except for the initial burst release which was based on diffusion. The presence of chitosan in the PLGA-NPs accelerated the rate of erosion of the nanoparticles and reduced the burst release of the drug. An understanding of the erosion mechanism and alteration in erosion by chitosan could give desirable and more uniform drug release kinetics from PLGA-NPs.     

Syntheses and structural characterizations of anionic borane-capped ammonia borane oligomers: evidence for ammonia borane H2 release via a base-promoted anionic dehydropolymerization mechanism

Studies of the activating effect of Verkade's base, 2,8,9-triisobutyl-2,5,8,9-tetraaza-1-phosphabicyclo[3.3.3]undecane (VB), on the rate and extent of H(2) release from ammonia borane (AB) have led to the syntheses and structural characterizations of three anionic aminoborane chain-growth products that provide direct support for anionic dehydropolymerization mechanistic steps in the initial stages of base-promoted AB H(2) release reactions. The salt VBH(+)[H(3)BNH(2)BH(2)NH(2)BH(3)](-) (1) containing a linear five-membered anionic aminoborane chain was produced in 74% yield via the room-temperature reaction of a 3:1 AB/VB mixture in fluorobenzene solvent, while the branched and linear-chain seven-membered anionic aminoborane oligomers VBH(+)[HB(NH(2)BH(3))(3)](-) (2a) and VBH(+)[H(3)BNH(2)BH(2)NH(2)BH(2)NH(2)BH(3)](-) (2b) were obtained from VB/AB reactions carried out at 50 °C for 5 days when the AB/VB ratio was increased to 4:1. X-ray crystal structure determinations confirmed that these compounds are the isoelectronic and isostructural analogues of the hydrocarbons n-pentane, 3-ethylpentane, and n-heptane, respectively. The structural determinations also revealed significant interionic B-H···H-N dihydrogen-bonding interactions in these anions that could enhance dehydrocoupling chain-growth reactions. Such mechanistic pathways for AB H(2) release, involving the initial formation of the previously known [H(3)BNH(2)BH(3)](-) anion followed by sequential dehydrocoupling of B-H and H-N groups of growing borane-capped aminoborane anions with AB, are supported by the fact that 1 was observed to react with an additional AB equivalent to form 2a and 2b.     

载药脂质体复合缺钙磷灰石骨水泥支架的研究

采用食盐颗粒浸出法制备了缺钙磷灰石水泥(CPC)多孔支架;用脂质体包裹盐酸万古霉素制备了载药脂质体。将它们两者结合,制备了脂质体载药复合缺钙磷灰石水泥(dl-CPC)支架。结果表明:缺钙CPC多孔支架能够将载药脂质体吸附在其大孔表面或微孔里;dl-CPC支架对MC3T3-E1细胞的生长没有负面影响,显示出良好的细胞相容性。此外,dl-CPC支架具有很好的抗菌性能,能够抑制大肠杆菌生长,抗菌率达99%(12 h)。dl-CPC支架浸泡在磷酸缓冲溶液中,释放药物的速度比较缓慢(前4周);而直接吸附药物的CPC支架,在1周内大部分药物释放出来,出现暴释现象。另结果表明:dl-CPC支架具有缓释药物和骨再生的双重功能,可用于骨缺损的修复及治疗慢性骨髓炎。     

Development and validation of LC methods with visible detection using pre-column derivatization and mass detection for the assay of voglibose

Two sensitive and selective liquid chromatographic methods were developed for the assay of voglibose (VB) and validated as per International Conference on Harmonization (ICH) guidelines. First method is based on the pre-column derivatization of VB followed by visible detection (LC-VD) and second method involves mass spectrometric detection (LC-MS). In LC-VD method, VB was derivatized with sodium metaperiodate and 3-methyl-2-benzothiazolinone hydrazone hydrochloride monohydrate (MBTH). The derivatized color product of VB (DCPVB) was run through Novapak C18 (300 × 3.9 mm, 4 μm) column using the mobile phase containing buffer (0.01 M mixture of sodium di hydrogen orthophosphate and disodium hydrogen orthophosphate, pH 6.0) and acetonitrile in 35:65 v/v ratio. The eluted DCPVB was monitored at 667 nm. The fixation of optimum conditions in LC-VD method is described. DCPVB structure was confirmed by mass spectral analysis. In LC-MS method, VB was passed through Venusil XBPPH (150 × 4.6 mm, 5 μm) column using a 95:5 v/v mixture of 0.01% formic acid and methanol as mobile phase. The assay concentrations of VB in pure form and in tablets for LC-VD and LC-MS methods are 25 and 5 ng ml⁻¹, respectively.     

Effects of the Molecular Weight of PLGA on Degradation and Drug Release In vitro from an mPEG-PLGA Nanocarrier

We successfully synthesized four kinds of copolymers with varying molecular weights of poly(lactide-co-glycolide)(PLGA) to yield methoxy-poly(ethylene glycol)-block-poly(lactide-co-glycolide)(mPEG-PLGA) nanocarriers:mPEG-PLGA(3k), mPEG-PLGA(9k), mPEG-PLGA(11k) and mPEG-PLGA(16k). An antitumor drug, 10-hydroxycamptothecin(HCPT), was encapsulated into the mPEG-PLGA nanocarrier cores by self-assembly in dialysis. The lower molecular weight nanocarriers degraded more quickly, resulting in mass loss, pH decline, and a rapid HCPT release rate in vitro. The degradation and drug release of the nanocarriers were dependent on the PLGA molecular weight. However, the larger molecular weight nanocarriers could not increase the loading content and encapsulation efficiency. Considering the antitumor effect of these nanocarriers, the mPEG-PLGA(9k) nanocarrier, which had the highest drug loading content[(7.72±0.57)%] and a relatively high encapsulation efficiency[(22.71±5.53)%], is an optimum agent for drug delivery.     

Dendritic polymers based on poly(ethylene glycol) -co- poly(glycolic acid) -co- methacrylate and 2.0 G -polyamidoamine- metharylamide: Design, characterization, and in vitro degradation, and drug release properties

In this paper, the properties of the complete degradation process of newly synthesized multi-block 2.0 G-polyamidoamine-double bond (PAMAM-DB) and resoluble poly (ethylene glycol) -co- poly (glycolic acid) -co- methacryloyl chloride (PEG-co-PGA-co-DB, 4KG5-DB) macromonomers were reported. Rectangular shaped samples were prepared by crosslinking the components using both chemical and photo initiators and exposure to UV light. The aims of the study were to examine the effects of the vitro degradation and drug delivery of the crosslinking group on the properties of photocrosslinked hydrogels. The experimental variable was PAMAM-DB: 4KG5-DB ratio. The effects of this variable on local PH, water uptake, mass loss, and drug release were explored. Polymers were characterized by ¹H NMR, ¹³C NMR, FT-IR, and SEM. Our study revealed that polymers with 40%, 50%, 60% 4KG5-DB (mass fraction) showed more excellent mechanical properties, 40% also showed outstanding vitro degradation properties. In vitro drug release, however, 60% drug released mechanism seemed to approach the Fickian diffusion and possessed more excellent drug release properties compared with formulation 40% and 50%. In general, an increase ratio of 4KG5-DB led to a higher density of tree-like polymer which resulted in slower of degradation and drug release. Incorporation of 4KG5-DB into the polymer was critical for maintaining integrity and increasing hydrophilicity during degradation. These results obtained suggest that this system could be potential as a material for bone replacement and controlled delivery of drugs.     

Disulfide-crosslinked Poly(L-glutamic acid) Grafted Mesoporous Silica Nanoparticles and Their Potential Application in Drug Delivery

Poly(L-glutamic acid)(PLGA) was grafted onto the surface of mesoporous silica nanoparticles(MSN) via the ring opening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride(BLG-NCA) and its subsequent deprotection of benzyl groups. The PLGA chains were cross-linked with cystamine, and thus forming a type of redox responsive drug delivery system(MSN-cPLGA). The structures were characterized by Fourier transform infrared spectrometry(FTIR), transmission electron microscopy(TEM) and energy disperse spectrometry(EDS), demonstrating that disulfide groups existed on the surfaces of MSN-cPLGA particles. The thermal gravimetric analysis(TGA) results show that the PLGA mass fraction is about 33.4% in the MSN-cPLGA hybrid. The in vitro drug release experiments showed that the MSN-cPLGA hybrid can realize the controlled release of model drugs(5-fluorouracil) in response to redox environment. Even 0.1 mmol/L dithiothreitol(DTT) can accelerate the drug release speed, and a concentration of 10.0 mmol/L DTT is higher enough to trigger the open of cross-linked PLGA network so as to realize rapid release of drugs. All the results demonstrate that the cross-linked PLGA chains on the surface of MSN could act as efficient gatekeepers to control the on-off of the pores, showing potential application in drug delivery system.     

功能化纳米粒子作为药物载体的研究

将合成的含有羧基侧基官能团的己内酯类聚合物, 用溶剂挥发与超声乳化相结合的方法制备成表面可供修饰的纳米粒子. 利用扫描电镜(SEM)研究了纳米粒子在水溶液中的形态. 使用5-氟脲嘧啶(5-FU)作为模型药物制备了载药纳米粒子, 利用紫外分光光度计法、差示扫描量热法(DSC)、X射线衍射法(XRD)研究了纳米粒子的载药及释放性能. 研究表明, 载药纳米粒子可以控制5-FU的释放速率. 释放时间可持续至96 h 以上, 符合Higuchi 动力学方程.     

Preparation of glucose-sensitive microcapsules with a porous membrane and functional gates

A glucose-sensitive microcapsule with a porous membrane and with linear-grafted polyacrylic acid (PAAC) chains and covalently bound glucose oxidase (GOD) enzymes in the membrane pores acting as functional gates was successfully prepared. Polyamide microcapsules with a porous membrane were prepared by interfacial polymerization, PAAC chains were grafted into the pores of the microcapsule membrane by plasma-graft pore-filling polymerization, and GOD enzymes were immobilized onto the PAAC-grafted microcapsules by a carbodiimide method. The release rates of model drug solutes from the fabricated microcapsules were significantly sensitive to the existence of glucose in the environmental solution. In solution, the release rate of either sodium chloride or VB(12) molecules from the microcapsules was low but increased dramatically in the presence of 0.2mol/L glucose. The prepared PAAC-grafted and GOD-immobilized microcapsules showed a reversible glucose-sensitive release characteristic. The proposed microcapsules provide a new mode for injection-type self-regulated drug delivery systems having the capability of adapting the release rate of drugs such as insulin in response to changes in glucose concentration, which is highly attractive for diabetes therapy.     

Modulation of the physicochemical state of interior agents to prepare controlled release liposomes

To prepare controlled release liposomes, freeze-drying of double emulsions (FDE) was employed to entrap a model drug, topotecan, which has been reported to tend to leak rapidly from vesicles. In addition, hydrogenated soy phosphatidylcholine (HSPC), N-(carbonyl-methoxypolyethyleneglycol2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (PEG-PE), and cholesterol (3:1:1, mass ratio) were used as the vesicle lipid. Different inner aqueous phases (W1) containing topotecan together with a variety of chemicals, such as citrate, sulfate, and divalent copper ions, were used to prepare W1/O/W2 double emulsions, which were then freeze-dried to obtain dry products. Upon rehydration, the dry products formed topotecan-entrapping unilamelar liposomes with an encapsulation efficiency of 80% and a mean diameter of less than 200 nm. The in vitro release experiments demonstrated that the drug release of topotecan-entrapping FDE liposomes could be successfully controlled through altering the state of the incorporated drug by means of protonation, precipitation, or forming a transition metal-complex. Specifically, the formulation of 300 mM CuSO₄ had a drug release half-life of 36 h. This novel method is a promising way to prepare controlled release liposomes that are more suitable for therapeutic application. In addition, the liposome formation mechanism was discussed based on micrographs and the size of the double emulsions and vesicles, as well as the small angle X-ray scattering pattern and transmission electron microscopy images.     

Synthesis and characterization of a vinyl‐terminated benzoxazine monomer and its blends with poly(ethylene oxide)

A vinyl‐terminated benzoxazine (VB‐a), which could be polymerized through ring‐opening polymerization, was synthesized through the Mannich condensation of bisphenol A, formaldehyde, and allylamine. This VB‐a monomer was then subjected to blending with poly(ethylene oxide) (PEO), followed by thermal curing, to form poly(VB‐a)/PEO blends. The specific interactions, miscibility, morphology, and thermal properties of these blends were investigated with Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry, dynamic mechanical analysis (DMA), and scanning electron microscopy (SEM). Before curing, we found that PEO was miscible with VB‐a, as evidenced by the existence of a single composition‐dependent glass transition temperature (T_g) for each composition. The FTIR spectra revealed the presence of hydrogen‐bonding interactions between the hydroxyl groups of poly(VB‐a) and the ether groups of PEO. Indeed, the ring‐opening reaction and subsequent polymerization of the benzoxazine were facilitated significantly by the presence of PEO. After curing, DMA results indicated that the 50/50 poly(VB‐a)/PEO blend exhibited two values of T_g: one broad peak appeared in the lower temperature region, whereas the other (at ca. 327 °C, in the higher temperature region) was higher than that of pristine poly(VB‐a) (301 °C). The presence of two glass transitions in the blend suggested that this blend system was only partially miscible. Moreover, SEM micrographs indicated that the poly(VB‐a)/PEO blends were heterogeneous. The volume fraction of PEO in the blends had a strong effect on the morphology. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 644–653, 2007     

Porous silicon: repeatability of generation?

A systematic investigation of the preparation of porous silicon layers (PSLs) on silicon wafers by anodic treatment in hydrofluoric acid/water/ethanol mixtures under various conditions was carried out with the aim to develop a repeatable process for homogeneous layers. The preparations were controlled by FTIR spectroscopy supported by TOF-SIMS measurements of the uppermost surface area. The repeatability of PLS generation was proved on the grounds of the IR-absorption of SiH_x and O_xSiH_y surface groups with respect to their frequencies and intensities. Uniform properties of PSLs are an essential assumption for defined chemical modifications.     

壳聚糖基多功能纳米药物载体的体外研究

制备了一种壳聚糖基多功能纳米药物载体系统, 并探讨了其体外释药性质. 合成了甲氨蝶呤-壳聚糖偶联物(MTX-CS), 甲氨喋呤(MTX)的取代度为6.3%; MTX-CS具有两亲性, 在水性介质中能自组装形成纳米粒子, 平均粒径为(269.5±18.3) nm, zeta电位为(25.7±0.9) mV. MTX-CS纳米粒子能有效包载抗血管生成药Combretastatin A-4(CA-4), 当药物/载体材料投料比为1∶4 时, 载药量为15.7%, 包封率为62.8%. 体外释放实验结果显示, CA-4释放较快, MTX释放缓慢, 有利于发挥2种药物的协同抗肿瘤作用.     

Thermosensitive Poly(N-isopropylacrylamide)-g -Polyamidoamine Dendrimer Derivatives: Preparation and the Drug Release Behaviors

Summary: A series of thermally responsive dendritic core-shell polymers were prepared based upon dendritic polyamidoamine (PAMAM), modified with carboxyl end-capped linear poly(N-isopropylacrylamide) (PNIPAAm-COOH) in different ratios via an esterification process to obtain PNIPAAm-g-PAMAM. The graft ratio of PNIPAAm could be adjusted by changing the feed ratio of PAMAM-OH to PNIPAAm-COOH and was verified by ¹H NMR and gel penetration chromatography (GPC). The lower critical solution temperature (LCST) of PNIPAAm-g-PAMAM evaluated by UV-vis spectrophotometer was about 32 °C. Indomethacin (IMC) as a model drug was loaded in the thermosensitive polymer-grafted dendrimer derivative and its release behavior was studied below and above its LCST (27 °C vs 37 °C). Results showed that the LCST of PNIPAAm-g-PAMAM was around 32 °C compared with that of the pure PNIPAAm. The release behavior of the indomethacin entrapped in the internal cavities of the PNIPAAm-g-PAMAM showed that almost 77% of the drug was cumulatively released at 27 °C after 10 hours, whereas only 20% was released at 37 °C. The release rate of IMC from the IMC/PNIPAAm-g-PAMAM complex at 37 °C is significantly slower than that at 27 °C, which indicates that the PNIPAAm chains grafted on the surface of PAMAM dendrimer could act as a channel switching on-off button through expending or contracting in response to the temperature variation and could control the drug release by varying the surrounding temperature.     

Design of controlled release system with multi-layers of powder

Pellets containing active ingredients were coated with water-insoluble powders, i.e. hydrogenated caster oil (Lubliwax (WAX)) and magnesium stearate (Mg-St). The influences of the structural difference of the sustained release layer and curing conditions on the drug release rate were investigated. Sodium valproate (VP-Na) was used as a highly water-soluble model drug. Drug release profiles were influenced by the combination of the WAX layer and the Mg-St layer. Even if the formula of sustained release layers were the same, drug release rate could be affected by the structural difference of the controlled release layer. The Mg-St layer was more effective in prolonging drug release than the WAX layer. Compared with single and double layer types, the triple layer (sandwich) type was most effective in obtaining a long sustained drug release. Heat-treatment retarded drug release mainly by increasing the density of the sustained release layer of the WAX. The Mg-St was effective in protecting the agglomeration between particles during heat-treatment. Optimal heat-treatment conditions were found to exist. Scanning electron microscopy (SEM) analysis indicated that heat-treatment caused the WAX to melt, formed a film-like structure and made the release layer dense. Furthermore, heat-treatment changed the release pattern of VP-Na from sustained release pellets with a multi-layer of powder, leading to zero-order release.     

Solid-state interactions and drug release of teicoplanin in binary combinations with peracetylated α-, β-, and γ-cyclodextrins

Triacetyl α-cyclodextrin, triacetyl β-cyclodextrin and triacetyl γ-cyclodextrin were tested as possible hydrophobic carriers to prolong the release of hydrophilic teicoplanin (TCP). Physical–chemical characterization of individual components, drug-carrier physical mixtures at 0.5, 0.67 and 0.75 mass fraction of carrier, and the respective interaction products by kneading or evaporative crystallization under microwave irradiation was carried out using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). In vitro drug release in pH 7.4 phosphate buffer at 37 °C was determined by intrinsic dissolution rate (IDR) measurements on non disintegrating compressed discs. Solid-state interactions of TCP with triacetyl α-cyclodextrin by evaporative crystallization and kneading and with triacetyl β-cyclodextrin by evaporative crystallization (probably resulting in carrier amorphization) were demonstrated. The role of carrier hydrophobicity, carrier mass fraction and preparation method of solid drug-carrier combinations on solid-state drug-carrier interactions and slowing down of TCP release was assessed. Modulation of drug release can be achieved using TCP-triacetyl γ-cyclodextrin combinations at 0.5 mass fraction of carrier.     

Influence of hydrophobe on the release behavior of vinyl acetate miniemulsion polymerization

Poly(vinyl acetate) (PVAc) nanoparticles containing antibiotic have been prepared by miniemulsion polymerization. To compare the effect of hydrophobe types, hexadecane and poly(vinyl acetate) were used as hydrophobe. The particle characteristics as the manufacturing condition were examined by particle size analyzer. As a result, the diameter of PVAc latexes was adjusted between 80 and 260 nm by homogenization conditions and amounts of surfactant. Also, the miniemulsion by using hexadecane showed the more long shelf stability and led to the more small particle size after polymerization, as compared with the case of using poly(vinyl acetate). This indicated that the use of poly(vinyl acetate) as a hydrophobe could not make the stable emulsion, but it could avoid volatile organic chemical problems in the final product. From the release profile of drug through UV spectra, the drug release was very slow and it could be seen that the release of drug encapsulated with PVAc was occurred with the polymer degradation.     

PLA/MSM缓释微球的制备及生物活性

采用膜乳化-液中干燥法制备出担载二甲基砜(MSM)的聚乳酸(PLA)微球(PLA/MSM), 并研究了膜孔径、 搅拌转速和MSM浓度对载药微球形貌、 尺寸、 载药量、 体外释放及细胞活性的影响; 采用场发射环境扫描电子显微镜(ESEM)观察微球形貌、 尺寸及分布, 用等离子体发射光谱(ICP-AES)法检测PLA/MSM微球载药量、 包封率及体外释放, 采用ESEM观察微球内部结构, 并通过体外细胞培养和噻唑蓝(MTT)法检测MC-3T3-E1细胞的增殖能力. 研究结果表明, 膜乳化法制备的载药微球规整, 呈典型的圆球状, 表面光滑, 内部有多孔结构. 当膜孔径为5.1 μm且搅拌转速为500 r/min时, PLA/MSM微球大小更为均一; 当体系中MSM质量分数为8.6%时, 载药量可达到77.43%. 随着膜孔径减小及药物浓度的增加, 体外释放速率加快, 但初期均无明显的突释现象, 约10 d后累积释放量达到89.2%. 细胞实验结果显示, 在膜孔径为5.1 μm且MSM质量分数为8.6%的条件下, 制备的载药微球在细胞培养7 d时表现出明显的促增殖作用.     

Preparation and characteristics of linoleic acid-grafted chitosan oligosaccharide micelles as a carrier for doxorubicin

The linoleic acid (LA)-grafted chitosan oligosaccharide (CSO) (CSO-LA) was synthesized in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and the effects of molecular weight of CSO and the charged amount of LA on the physicochemical properties of CSO-LA were investigated, such as CMC, graft ratio, size, zeta potential. The results showed that these chitosan derivatives were able to self-assemble and form spherical shape polymeric micelles with the size range of 150.7–213.9 nm and the zeta potential range of 57.9–79.9 mV, depending on molecular weight of CSO and the charged amount of LA. Using doxorubicin (DOX) as a model drug, the DOX-loaded CSO-LA micelles were prepared by dialysis method. The drug encapsulation efficiencies (EE) of DOX-loaded CSO-LA micelles were as high as about 75%. The sizes of DOX-loaded CSO-LA micelles with 20% charged DOX (relating the mass of CSO-LA) were near 200 nm, and the drug loading (DL) capacity could reach up to 15%. The in vitro release studies indicated that the drug release from the DOX-loaded CSO-LA micelles was reduced with increasing the graft ratio of CSO-LA, due to the enhanced hydrophobic interaction between hydrophobic drug and hydrophobic segments of CSO-LA. Moreover, the drug release rate from CSO-LA micelles was faster with the drug loading. These data suggested the possible utilization of the amphiphilic micellar chitosan derivatives as carriers for hydrophobic drugs for improving their delivery and release properties.