PLA/PEG/PLA三嵌段共聚物载药纳米胶囊的制备及表征

用于药物控释体系的微胶束具有实心微球结构,药物分子主要吸附于微球表面,极易脱落,在释药初期有明显的突释效应;而微胶囊的药物主要集中于囊心部分,药物通过扩散作用以及高分子膜的降解而逐渐释放到环境中,因而更有利于药物分子平稳、缓慢地释放．对于自然界中能够自发形成微胶囊的小分子材料,其分子中往往具有一个较小的亲水部分和一个相对较大的憎水部分,     

Preparation of albumin—PAA nanocapsules and their controlled release behavior for drugs

New kinds of narrowly distributed protein‐based nanoparticles, bovine serum albumin‐Poly (acrylic acid) (BSA/PAA) nanospheres, and nanocapsules were prepared via in situ polymerization, swelling, and re‐aggregation. The structure and morphology of the nanospheres were characterized by UV‐Vis, FT‐IR, DLS, and TEM. The stability of the BSA/PAA nanospheres and nanocapsules was increased when their skeletons were fixed by cross‐linked agents. The nanospheres carried a positive charge and their size was about 80–110 nm. The protein‐based nanocapsules were stimuli‐responsive with pH value and their hydrodynamic diameter varied from 70 to 230 nm with changes of pH. In vitro release experiments of Rhodamine B and Doxorubicin hydrochloride showed that these biopolymer nanoparticles provided a controlled release of the entrapped drugs for 300 hr. Copyright © 2009 John Wiley & Sons, Ltd.     

Crosslinked Polymeric Nanocapsules Via Surface-initiated Atom Transfer Radical Polymerization from SiO2 Nano-templates

The aim of the present work was to develop the crosslinked polymeric nanocapsules for drug delivery from the SiO₂ nano-templates via surface-initiated atom transfer radical polymerization (SI-ATRP) technique. The crosslinked polymeric nanocapsules were fabricated via the SI-ATRP of 2-hydroxyethyl acrylate (HEA) from initiator modified silica nano-templates. After the hydroxyl side-groups of the polymer grafted silica nanoparticles (SN@PHEA) were crosslinked with hexamethylene diisocyanate (HDI), the silica templates encapsulated in the crosslinked polymer shells were removed by being etched with HF to produce the crosslinked polymeric nanocapsules. The diameter of the polymeric nanocapsules is in the range of 20–40 nm, characterized by transmission electron microscopy (TEM).     

Preparation of highly dispersed core/shell-type titania nanocapsules containing a single Ag nanoparticle

Core/shell-type titania nanocapsules containing a single Ag nanoparticle were prepared. Ag nanoparticles were prepared using the reduction of silver nitrate with hydrazine in the presence of cetyltrimethylammonium bromide (CTAB) as protective agent. The sol-gel reaction of titanium tetraisopropoxide (TTIP) was used to prepare core/shell-type titania nanocapsules with CTAB-coated Ag nanoparticles as the core. TEM observations revealed that the size of the core (Ag particle) and the thickness of the shell (titania) of the core/shell particles obtained are about 10 nm and 5-10 nm, respectively. In addition, the nanocapsules were found to be dispersed in the medium as individual particles without aggregation. Moreover, titania coating caused the surface plasmon absorption of Ag nanoparticles to shift toward the longer wavelength side.     

Retinyl palmitate polymeric nanocapsules as carriers of bioactives

Nanocapsules containing poly(d,l-lactide) shell and retinyl palmitate core have been prepared by the pre-formed polymer interfacial deposition method. Dynamic light scattering measurements yielded an average hydrodynamic diameter of ～220nm and a polydispersity index of ～0.12. Small-angle neutron scattering experiments revealed the presence of two populations of nanocapsules of core diameters ～192 and 65nm. Freeze fracture transmission electron microscopy showed a polydisperse population of nanocapsules (NC), with a poly(d,l-lactide) shell thickness between 11 and 3nm. For comparison purposes, nanoemulsions (NE, no polymer) and nanospheres (NS, polymer matrix) were also prepared. Each type of nanoparticles exhibited a different morphology (when examined by electron microscopy), in particular NC showed deformability by capillary adhesion. All three types of nanoparticles successfully encapsulated the poorly water-soluble molecules baicalein and benzophenone-3. The thermal behavior of the various nanoparticles was different to a physical mixture of its individual components. Cytotoxicity and phototoxicity assays, performed in human keratinocytes (HaCaT) and murine fibroblasts (BALB/c 3T3), showed that the NC were only cytotoxic at high concentrations. In vitro release studies of benzophenone-3, by the dialysis bag method using NC and NS, showed a sustained release; however, permeation studies using plastic surgery human abdominal skin in Franz diffusion cells showed that a higher amount of benzophenone-3 from NC penetrated into the skin, most probably due to the deformable nature of these nanoparticles.     

Synthesis of liquid‐filled nanocapsules via the miniemulsion technique

This study describes the synthesis of well‐defined nanocapsules via the miniemulsion technique. Pentaerythritol tetrakis(3‐mercaptopropionate) (TetraThiol) or 1,6‐hexanediol di(endo, exo‐norborn‐2‐ene‐5‐carboxylate) (DiNorbornene) is used as the oil phase. TetraThiol is encapsulated via the miniemulsion technique without polymerization, as this monomer would simultaneously act as a chain‐transfer agent, and DiNorbornene is encapsulated via miniemulsion polymerization of styrene. Various styrene‐maleic anhydride (PSMA) copolymers and poly(styrene‐maleic anhydride)‐block‐polystyrene (PSMA‐b‐PS) block copolymers were used as surfactant for the synthesis of well‐defined nanocapsules with TetraThiol as the core material. The nanocapsules had a diameter of 150–350 nm and the particle size distribution was narrow. The use of PSMA‐b‐PS block copolymers as surfactant in combination with post‐addition of formaldehyde provided improved stability to the nanocapsules. DiNorbornene was encapsulated via miniemulsion polymerization of styrene, and a stable latex with a bimodal particle size distribution was obtained. The distribution of small particles had a size of 60 nm and the distribution of large particles had a size of 150 nm. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

聚α-氰基丙烯酸丁酯纳米微囊的制备研究

通过界面聚合方法合成了聚α－氰基丙烯酸丁酯纳米微囊，研究了搅拌速率、乙醇浓度等聚合条件对粒径的影响，获得了平均粒径为100nm，壁厚为15nm的纳米微囊。     

Biotinylated thermoresponsive core cross-linked nanoparticles via RAFT polymerization and "click" chemistry

A straightforward approach to the synthesis of "clickable" thermoresponsive core cross-linked (CCL) nanoparticles was developed. This approach was based on reversible addition-fragmentation chain transfer (RAFT) radical cross-linking polymerization of styrene and divinylbenzene with azide-functionalized poly(N-isopropylacrylamide) (PNIPAM-N(3)) as macro chain transfer agent in a selective solvent. Spherical nanoparticles with a diameter of 12nm were obtained after 24h polymerization. When the lyophilized CCL nanoparticles were dispersed in THF, spherical nanoparticles were observed, confirming the stability of CCL nanoparticles. The transmission electron microscopy (TEM) studies demonstrated that spherical nanoparticles and wormlike structure coexisted in the aqueous solution. The CCL nanoparticles have a lower critical solution temperature (LCST) at about 29.6°C, a little lower than that of PNIPAM homopolymer. Biotin molecules were conjugated to the surface of CCL nanoparticles via "click" chemistry in aqueous media. After bioconjugation, the LCST shifted to 28.3°C. The bioavailability of biotin to protein avidin was evaluated by a 4'-hydroxyazobenzene-2-carboxylic acid/avidin (HABA/avidin) binding assay and TEM.     

An improved interfacial coacervation technique to fabricate biodegradable nanocapsules of an aqueous peptide solution from polylactide and its block copolymers with poly(ethylene glycol)

ABA block copolymers of polylactide and poly(ethylene glycol) as amphiphilic bioabsorbable polymers were synthesized by the ring-opening polymerization of dl- lactide onto poly(ethylene glycol) (PEG 2000 or PEG 6000) and their structures were characterized on the basis of proton NMR. Biodegradable nanocapsules of an aqueous insulin solution were prepared from the block copolymers and polylactide by an improved interfacial coacervation technique. The results showed that the diameters of the nanocapsules were mainly dependent on the ratio of the two chains in the block polymers. The size of the nanocapsules decreased with an increase in the amount of surfactant used. More insulin solution resulted in an enlargement of the nanocapsules in diameter. In an optimum condition, biodegradable nanocapsules could be achieved with a size around 250 nm with a narrow distribution. The encapsulation percentages of insulin were larger in the nanocapsules from the PEG 2000 copolymers than in those from the PEG 6000 analogs and changed with the ratios of the blocks in the block copolymers. Received: 17 July 2000 Accepted: 24 November 2000     

Synthesis of polymeric nanocapsules by radical UV‐activated interface‐emulsion polymerization

A new methodology is reported that allows a better control of the synthesis of polymeric core–shell nanocapsules. These nanocapsules were made of biocompatible polymers, obtained from poly(ethylene glycol)diacrylate and poly(ethylene glycol) methyl ether methacrylate, and were used as carrier for curcumin as therapeutic agent. The impact of manufacturing factors (time of sonication, time of UV irradiation, and type of monomer) was investigated in relation to the average size of nanocapsules, their distribution, shape, composition, stability, and their capability to deliver curcumin. We successfully synthesized core–shell nanocapsules in various sizes, ranging from 80 nm to 300 nm, by acting either on the process conditions or on the composition of the monomer mixture. This wide range of sizes makes the method here proposed very promising for the production of nanocarriers. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 3357–3369     

Facile fabrication of thermally responsive Pluronic F127-based nanocapsules for controlled release of doxorubicin hydrochloride

Novel core–shell-structured Pluronic-based nanocapsules with thermally responsive properties were successfully prepared using a modified emulsification/solvent evaporation method. The nanocapsules were constructed through the cross-linking reaction between p-nitrophenyl-activated Pluronic F127 and hyaluronic acid (HA) (named Pluronic F127/HA) or poly(ε-lysine) (PL) (named Pluronic F127/PL) at the organic/aqueous interface. The formation, size, and thermal responsiveness of the nanocapsules were characterized by ¹H NMR, transmission electron microscopy (TEM) and dynamic light scattering (DLS). The resultant shell-cross-linked nanocapsules exhibit a larger volume transformation (26 times change in volume for Pluronic F127/HA and 31 times for Pluronic F127/PL) over a temperature range of 4–37 °C because of the temperature-dependent dehydration of cross-linked Pluronic F127 polymer chains. The nanocapsules are about 72?±?4 nm (polydispersity index [PDI]?=?0.08) for Pluronic F127/PL (69?±?5 nm, PDI?=?0.10 for Pluronic F127/HA) at 37 °C with narrow size distribution and expand to about 226?±?23 nm (PDI?=?0.34) for Pluronic F127/PL (206?±?20 nm, PDI?=?0.3) for Pluronic F127/HA at 4 °C with broad size distribution in aqueous solutions. The nanocapsules were used to encapsulate and control the release of doxorubicin hydrochloride (DOX·HCl) in aqueous solution. DOX·HCl was physically encapsulated in the nanocapsules using a soaking–freeze-drying–heating procedure. The release curve and release kinetics disclosed that the thermally responsive hollow nanocapsules are good carries for drug delivery.     

Fabrication, characterization, and supercooling suppression of nanoencapsulated n-octadecane with methyl methacrylate–octadecyl methacrylate copolymer shell

Supercooling of micro- and nanoencapsulated phase change material is widely observed as their diameters depress to a limitation upon cooling. The aim of this study is to suppress the supercooling of nanoencapsulated n-octadecane (NanoC18) using a novel copolymer consisting of long n-alkyl side chains as shell. Nanoencapsulations of n-octadecane with various compositions of poly(methyl methacrylate-co-octadecyl methacrylate) copolymer as shells were carried out by means of miniemulsion polymerization. Fabrication, morphology, diameter distributions, phase change behaviours, and thermal stabilities of nanocapsules were investigated using Fourier transformed infrared spectroscopy, a field-emission scanning electron microscope, a transmission electron microscope, particle size distribution analysis, differential scanning calorimetry, and thermogravimetric analysis. The results indicate that a series of nanocapsules with core/shell structure and spherical shapes are fabricated with average diameters ranging from 373 to 398 nm. The average thickness of the shells is about 60 nm. All the NanoC18 crystallize into a stable triclinic phase via a metastable rotator phase (R_I) from the liquid phase. The crystallization temperature of n-octadecane within poly(methyl methacrylate) nanocapsules is considerably lower than that in bulk phase. Supercooling is effectively suppressed using the comb-like copolymer with crystallizable n-octadecyl side chains as shell. Octadecyl methacrylate is not only employed as a reactive costabilizer to suppress the influence of Ostwald ripening during the formation of nanocapsules but also as a functional monomer in the composition of the copolymer shell in order to suppress the supercooling of NanoC18.     

Synthesis of polymeric ionic liquid microsphere/Pt nanoparticle hybrids for electrocatalytic oxidation of methanol and catalytic oxidation of benzyl alcohol

Herein, we present a facile approach for the synthesis of polymeric ionic liquids (PILs) microspheres for metal scavenging and catalysis. Crosslinked poly(1‐butyl‐3‐vinylimidazolium bromide) microspheres with the diameter of about 200 nm were synthesized via miniemulsion polymerization, in which 1,4‐di(vinylimidazolium) butane bisbromide was added as the crosslinker. Anion exchange of PIL microspheres with Pt precursor and followed by the reduction of Pt ions produced PIL microsphere supported Pt nanoparticle hybrids. The synthesized Pt nanoparticles with a diameter of about 2 nm are uniformly dispersed and strongly bound to the surface of PIL microspheres. The catalytic performances of PIL/Pt nanoparticle hybrids were evaluated for both the electrocatalytic oxidation of methanol and oxidation of benzyl alcohol. The PIL/Pt nanoparticle hybrids show better electrocatalytic activity towards the electrooxidation of methanol than pure Pt nanoparticles. Furthermore, they are effective and easily reusable catalysts for the selective oxidation of benzyl alcohol in aqueous reaction media, demonstrating that the synthesized PIL microspheres are suitable scaffolds for heterogeneous catalysts Pt. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

Near‐Infrared Triggered Decomposition of Nanocapsules with High Tumor Accumulation and Stimuli Responsive Fast Elimination

A near‐infrared (NIR) induced decomposable polymer nanocapsule is demonstrated. The nanocapsules are fabricated based on layer‐by‐layer co‐assembly of azobenzene functionalized polymers and up/downconversion nanoparticles (U/DCNPs). When the nanocapsules are exposed to 980 nm light, ultraviolet/visible photons emitted by the U/DCNPs can trigger the photoisomerization of azobenzene groups in the framework. The nanocapsules could decompose from large‐sized nanocapsule to small U/DCNPs. Owing to their optimized original size (ca. 180 nm), the nanocapsules can effectively avoid biological barriers, provide a long blood circulation (ca. 5 h, half‐life time) and achieve four‐fold tumor accumulation. It can fast eliminate from tumor within one hour and release the loaded drugs for chemotherapy after NIR‐induced dissociation from initial 180 nm capsules to small 20 nm U/DCNPs.     

"Two-in-one" fabrication of Fe3O4/MePEG-PLA composite nanocapsules as a potential ultrasonic/MRI dual contrast agent

A new method for the fabrication of Fe(3)O(4) nanoparticles enveloped by polymeric nanocapsules is proposed. This method is characterized by combining a double emulsification with the interfacial coprecipitation of iron salts to form Fe(3)O(4)/polymer composite nanocapsules in a single step. To demonstrate the viability of this approach, methoxy poly(ethylene glycol)-poly(lactide) (MePLEG) was chosen as the shell material for Fe(3)O(4)/MePLEG nanocapsules. In addition to the versatility offered for fabricating nanocapsules with different shell materials, the method was found to be convenient for adjusting the magnetite content of the nanocapsules from 0 to 43%. In addition to their confirmed T(2)-weighted magnetic resonance imaging (MRI) enhancement, the resultant composite nanocapsules display much more obvious acoustic responses than MePLEG nanocapsules in an acoustic investigation. Furthermore, the low toxicity of these composite nanocapsules, as confirmed by our study, combined with their magnetic and acoustic properties ensure that these composite nanocapsules have great potential in acting as ultrasonic/MRI dual contrast agents.     

沉淀聚合制备粒径可控的温度响应型蛋白纳米胶囊

以牛血清蛋白(BSA)为模型蛋白,N-异丙基丙烯酰胺(NIPAM)为单体,N,N'-亚甲基双丙烯酰胺(BIS)为交联剂,采用原位沉淀聚合法制备了单分散的温度响应型蛋白纳米胶囊(nBSA).通过调整单体与蛋白的比例制备了粒径大小不同的含有单个蛋白分子的BSA纳米胶囊.采用基质辅助激光解吸电离飞行时间质谱仪(MALDI-TOF MS)、透射电镜(TEM)和动态光散射仪(DLS)等对BSA蛋白的修饰度,nBSA的形貌和结构,以及温度响应性能进行了表征,并用HeLa细胞对nBSA的体外安全性进行了初步评价.结果表明,在一定范围内,随着单体和蛋白比例的升高,蛋白纳米胶囊的粒径也逐渐增大,且在7.4～17 nm之间可控,而nBSA的响应温度则逐渐减小在33～41℃之间可控;制备的nBSA单分散性较好;nBSA具有温度响应性能,当环境温度高于其响应温度时,nBSA的粒径可显著增大16～33倍,且这种变化随温度呈现可逆性,并通过对nBSA细胞毒性的初步考察,评价将其用于生物领域的潜力.     

Enhanced Sunscreen Effects via Layer-By-Layer Self-Assembly of Chitosan/Sodium Alginate/Calcium Chloride/EHA

The sunscreen nanocapsules were successfully synthesized by the way of layer-by-layer self-assembly using charged droplets (prepared by emulsification of LAD-30, Tween-80 and EHA (2-Ethylhexyl-4-dimethylaminobenzoate)) as templates. Chitosan/sodium alginate/calcium chloride were selected as wall materials to wrap EHA. The emulsions with the ratio of Tween-80 to EHA (1:1) were stable. A stable NEI negative emulsion can be obtained when the ratio of Tween-80 and LAD-30 was 9:1. Chitosan solutions (50 kDa, 0.25 mg/mL) and sodium alginate solutions (0.5 mg/mL) were selected to prepare nanocapsules. The nanocapsules were characterized via some physico-chemical methods. Based on the synergistic effects of the electrostatic interaction between wall materials and emulsifiers, EHA was effectively encapsulated. DLS and TEM showed that the sunscreen nanocapsules were dispersed in a spherical shape with nano-size, with the increasing number of assembly layers, the size increased from 155 nm (NEI) to 189 nm (NEII) to 201 nm (NEIII) and 205 nm after solidification. The release studies in vitro showed sustained release behavior of the nanocapsules were observed with the increase of the number of deposition layers, implying a good coating effect. The sunscreen nanocapsules could control less than 50% the release of EHA after crosslinking of calcium chloride and sodium alginate, which also could effectively avoid the stimulation of the sun protection agent on the skin.     

Acid-Labile Polyvinylamine Micro- and Nanogel Capsules

Hollow nanoparticles represent an emerging area of development for the encapsulation of active ingredients. Expanding the capabilities of these nanomaterials will require continued efforts to infill properties such as size control, biodegradability, and environmental responsiveness. Acid-labile poly(N-vinylformamide) (PNVF) nanocapsules were synthesized by free radical polymerization of N-vinylformamide on the surface of silica nanoparticles. Polymerization in the presence of a novel crosslinker that contains an acid-labile ketal facilitated stable etching of silica nanoparticle templates using sodium hydroxide and recovery of degradable PNVF nanocapsules. The formamido side group of PNVF was then hydrolyzed by extended exposure to sodium hydroxide to produce polyvinylamine (PVAm) micro- and nanocapsules. Both capsule types demonstrated an increasing dissolution rate as pH decreased. In addition, PVAm nanocapsules exhibited swelling in proportion to the relative charge density of the PVAm network (a function of the degree of formamide hydrolysis and pH), presumably due to the repulsion of positively charged amino groups within the elastic shell network. The synthetic approaches reported provide methods to endow nanocapsules with key attributes such as size control, pH sensitive degradation, swelling in response to pH, and amine functionality.     

Preparation and Characterization of Poly(D,L-Lactide) (PLA) and Poly(D,L-Lactide)-Poly(Ethylene Glycol) (PLA-PEG) Nanocapsules Containing Antitumoral Agent Methotrexate

Summary: The aims of the present work were to prepare and characterize nanocapsules containing antitumoral agent methotrexate (MTX) from poly(D ,L -lactide) (PLA) and poly(D ,L -lactide)-poly(ethylene glycol) diblock copolymer (PLA-PEG) with the purpose of administrating this drug by topical ocular route for primary ocular lymphoma treatment. Nanocapsules were prepared by the interfacial deposition of preformed polymer. The influences of the initial amount of MTX on the encapsulation efficiency, drug recovery and drug content, as well as the physicochemical properties of the particles were evaluated. The particle mean diameters were 246 and 146 nm, and zeta potential values were −38.8 and −33.6 mV, for the MTX-loaded nanocapsules prepared from PLA and PLA-PEG, respectively. The methotrexate content in the particles increased with the increasing in the drug amount added to the formulations, but the drug recovery decreased significantly. After 4 h of in vitro release, 28 and 86% of MTX was released from PLA and PLA-PEG nanocapsules, respectively.     

Dissolution of iron oxide nanoparticles inside polymer nanocapsules

The structure of poly(organosiloxane) nanocapsules partially filled with iron oxide cores of different sizes was revealed by small angle X-ray scattering and X-ray diffraction. The nanocapsules are synthesized by the formation of a poly(organosiloxane) shell around iron oxide nanoparticles and the simultaneous partial dissolution of these cores. Due to the high scattering contrast of the iron oxide cores compared to the polymer shell, the particle size distribution of the cores inside the capsules can be measured by small angle X-ray scattering. Additional information can be revealed by X-ray diffraction, which gives insights into the formation of the polymer network and the structure of the iron oxide cores. The study shows how the crystallinity and size of the nanoparticles as well as the shape and width of the size distribution can be altered by the synthesis parameters.