紫杉醇pH敏感嵌段共聚物胶束的制备与体外评价

目的应用pH敏感聚组氨酸-聚乳酸-聚乙二醇(poly(L-histidine)-poly(D,L-lactide)-poly(ethylene glycol),PHis-PLA-mPEG)聚合物为载体材料,采用溶剂挥发法制备紫杉醇pH敏感嵌段共聚物胶束,并对其体外性质进行评价。方法采用芘荧光探针法测定PHis-PLA-mPEG聚合物的临界胶束浓度(critical micelle concentration,CMC);超速离心法测定紫杉醇共聚物胶束的包封率和载药量;分别利用动态光散射法和Zeta电位分析仪对胶束的粒径分布和表面电位进行测定;采用透析法测定载药胶束在不同pH条件下的体外释药行为。结果 PHis-PLA-mPEG临界胶束质量浓度为8.9 mg·L-1,胶束载药量质量分数为8%;包封率可达90%以上;载药胶束的平均粒径为150.2nm,PDI为0.097,粒度分布较窄,Zeta电位为-14.3 mV;载药胶束在弱酸性条件下,药物释放行为明显加快。结论 PHis-PLA-mPEG聚合物载体材料具有较好的pH敏感释药行为,其作为抗肿瘤药物的靶向传递系统具有较好的应用前景。     

多西他赛pH敏感型聚(2-乙基-2-噁唑啉)-聚(D,L-丙交酯)自组装胶束的制备及其性质

目的利用两亲性嵌段共聚物聚(2-乙基-2-噁唑啉)-聚(D,L-丙交酯)[poly(2-ethyl-2-oxazo-line)-poly(D,L-lactide),PEOz-PDLLA]的自组装性能制备pH敏感型多西他赛胶束,并对其相关性质进行考察。方法运用阳离子开环聚合反应得到PEOz-PDLLA,通过FITR、1H-NMR和凝胶色谱法对其结构进行表征,采用电位滴定法测定共聚物pKa,应用荧光探针技术确定临界胶束浓度(criticalm icelle concentration,CMC)。动态光散射法和Zeta电位测试仪测定胶束的粒径和Zeta电位。以薄膜分散法包载多西他赛,并用透析法研究载药胶束的体外释放度。结果PEOz-PDLLA的亲水/疏水段分子质量比值为0.76,pKa为6.41,CMC为0.8×10-3g.L-1。载药胶束包封率为94.9%、载药量质量分数为8.7%、平均粒径为(35.3±4.9)nm、Zeta电位为(25.51±2.14)mV,在pH5.0的释放介质中释药速度加快。结论PEOz-PDLLA嵌段共聚物可自组装形成胶束,高效包载多西他赛,体外释放具有pH敏感性。     

紫杉醇MPEG-PCL纳米粒的制备、表征及其体外释药行为研究

目的 以聚乙二醇单甲醚-聚己内酯(MPEG-PCL)为载体制备紫杉醇MPEG-PCL纳米粒并对其体外释放行为进行考察。方法 采用开环聚合法合成MPEG-PCL共聚物,采用核磁共振波谱仪(¹H-NMR)、傅里叶红外光谱仪(FTIR)对其进行表征;通过共沉淀法制备了紫杉醇MPEG-PCL纳米粒,并测定了粒径分布、Zeta电位、结构特征、包封率以及载药量;同时以磷酸盐缓冲溶液(pH=7.4)为释放介质考察其体外释放行为。结果 成功合成了相对分子质量为4 875的MPEG-PCL共聚物。透射电镜结果显示紫杉醇MPEG-PCL纳米粒具有规则的球形结构,纳米粒的平均粒径为(102.3±3.5)nm,PDI=0.102,药物包封率和载药量分别为(95.6±3.2)%和(8.5±0.4)%。体外释放结果显示紫杉醇可以缓慢的从MPEG-PCL纳米粒中释放出来。结论 MPEG-PCL共聚物是紫杉醇的良好载体,所制备的纳米粒具有包封率和载药量高、药物释放缓慢的特点。     

水溶性壳聚糖包覆多西他赛纳米脂质体的制备及性能研究

目的:制备羧甲基壳聚糖包衣多西他赛纳米脂质体,并考察其体外释放度。方法:采用薄膜分散法制备多西他赛阳离子脂质体,并用不同浓度的羧甲基壳聚糖包覆阳离子脂质体;用超滤法测定其包封率;用激光电位粒径测定仪分别测定其Zeta电位和粒径大小,并用透射电镜观察其形态;用透析法考察其体外释药性质。结果:所制的羧甲基壳聚糖包覆的脂质体包封率达99.98%;Zeta电位为-12.8 mV,平均粒径为(150±17)nm。结论:本实验制备的羧甲基壳聚糖包衣多西他赛纳米脂质体具有高包封率,粒径大小均匀,体外能显著延缓药物释放的性质。     

薄膜-超声法制备芦丁固体脂质纳米粒的研究

目的优化薄膜-超声法制备芦丁固体脂质纳米粒的处方。方法以包封率为指标,采用正交设计优化法考察硬脂酸和大豆卵磷脂的用量、吐温-80和聚乙二醇-400的体积分数对包封率的影响,优选最佳处方。用透射电镜观察外观形态,用电位/纳米粒度分析仪分析纳米粒的粒径及Zeta电位,用透析法评价体外释药特征。结果以最佳处方制备的芦丁固体脂质纳米粒呈类球形,平均粒径为195.8±11nm,Zeta电位为-20.65±0.6mV,平均包封率为86.31%,72h体外累积释放87.32%。结论按最佳处方工艺制备的芦丁固体脂质纳米粒具有较高的包封率和较好的缓释效果。     

基因载体PEG化壳聚糖的制备及其表征

目的：用亲水性的聚乙二醇对壳聚糖进行改性，制备适用于基因转染的非病毒类裁体。方法：合成步骤共分三步。首先通过有机合成，将甲氧基聚乙二醇(mPEG)的羟基末端依次活化成为羧基和琥珀酰亚胺端基，形成mPEG-COOH活化物和mPEG-COONSu活化物；然后将亲水性的mPEG-COONSu活化物接枝到壳聚糖的氨基侧链上，得到改性了的壳聚糖-聚乙二醇接枝产物，应用波谱技术FTIR，^1H-NMR，^13C-NMR对中间产物和最终产物进行了表征。结果：在FTIR谱图上基本找到mPEG-COOH，mPEG-COONSu的特征峰；^1H-NMR再一次确认mPEG-COONSu的合成；^13C-NMR确认了壳聚糖-聚乙二醇接枝产物的存在。结论：mPEG-COONSu活化物通过接枝反应对壳聚糖进行改性，得到了PBG化壳聚糖。     

聚谷氨酸苄酯/聚乙二醇嵌段共聚物膜的透药性

目的：研究聚谷氨酸苄酯/聚乙二醇/聚谷氨酸苄酯（GEG）嵌段共聚物膜对氟尿嘧啶（5-fluorouracil，5-Fu）、氢化可的松琥珀酸钠的透过性。方法：通过实验室制备的药物渗透装置，用紫外分光光度计测定透过药物的浓度，计算药物的渗透系数，绘制透药曲线。结果：对同一种药物，随着共聚物中聚乙二醇（PEG）含量的增加，膜的传质能力变大；对同一种聚合物膜，随着药物的分子量增加，其传质能力变小。结论：聚合物膜有良好的药物通透性。     

5-氟尿嘧啶聚乙二醇-聚十六烷基氰丙烯酸酯纳米粒的制备

目的:以聚乙二醇-聚十六烷基氰丙烯酸酯(PEG-PHDCA)聚合物制备5-氟尿嘧啶(5-Fu)纳米粒,并对其进行体外释药研究.方法:采用溶剂扩散法制备5-Fu PEG-PHDCA纳米粒,在单因素基础上采用正交设计法优化得到最佳处方,并对5-Fu聚合物纳米粒的粒径、Zeta电位、载药量、包封率和体外释放进行了研究.结果:制得的5-Fu聚合物纳米粒的平均粒径为132 nm,Zeta电位为-(12±2)V,载药量为12.3%,包封率为48.8%.体外释放研究发现,5-Fu PEG-PHDCA纳米粒释药近似符合Higuchi释药模型:Q=0.564 4+8.386t1/2(r=0.996 0).结论:采用溶剂扩散法制备5-Fu聚合物纳米粒方法简单,重现性好,其体外释放显示出明显缓释作用.     

羟基喜树碱阳离子聚合物纳米粒的制备和体外性质评价

目的:合成直链聚乙烯亚胺(linear polyethyleneimine,LPEI)接枝单甲氧基聚乙二醇(methoxypolyethylene,mPEG)/聚己内酯(polyε-Caprolactone,PCL)的双亲性阳离子聚合物(mPEG-LPEI-PCL)用于制备阳离子型10-羟基喜树碱纳米粒(10-hydroxycamptothecin nanoparticles,HCPT-NPs),并对其体外性质进行评价。方法:通过IR和1H-NMR表征聚合物结构;采用改进的薄膜分散法制备HCPT-NPs,然后考察纳米制剂的粒径、电势、包封率、稳定性和形态,透析法研究HCPT-NPs的体外释放。结果:HCPT-NPs平均粒径为(155.6±9.6)nm,Zeta电位为(29.6±3.2)mV,包封率和载药量分别为(92.6±1.1)%和(4.49±0.02)%,释放速率随pH值升高而加快。结论:成功合成双亲性聚合物mPEG-LPEI-PCL,该聚合物能自组装形成核-壳结构纳米粒,4℃下稳定性良好。     

棓丙酯脂质体的制备与表征

目的制备棓丙酯脂质体,并对其进行理化性质的表征和释放度的评价。方法采用薄膜分散法制备棓丙酯脂质体,超滤离心法测定脂质体的包封率,正交设计优化处方,并对其包封率、粒径、Zeta电位、形态及体外释放行为进行综合评价。结果正交设计优化最终处方为磷脂浓度5 mg.mL-1、药脂比1∶5、磷脂胆固醇比5∶1、水化介质离子强度20 mmol.mL-1,所得脂质体包封率为89.6%、粒径为181.3 nm、Zeta电位为-21.8 mV、4 h体外释放达到80%。结论制备的棓丙酯脂质体包封率高,粒径小而均一,体外释放完全。     

重组人肿瘤坏死因子隐形纳米粒的制备及其稳定性

目的制备3种不同粒径和表面为3种不同分子量(2 000，5 000和10 000)的单甲氧基聚乙二醇(MePEG)修饰的重组人肿瘤坏死因子隐形纳米粒，考察纳米粒胶体溶液的稳定性。方法合成载体材料聚乙二醇化聚十六烷基氰基丙烯酸酯(MePEG-PHDCA)和聚十六烷基氰基丙烯酸酯(PHDCA)，用FTIR,¹HNMR,¹³CNMR和GPC技术对其表征。以均匀设计法优化制备各类隐形和普通纳米粒。将纳米粒胶体溶液在2-8 ℃存放4周，观察粒径变化。结果FTIR,¹HNMR,¹³CNMR图谱与MePEG-PHDCA和PHDCA的结构相符，GPC表明两类载体材料分子量分布较窄。纳米粒包封率较高，粒径分别约为80,170和240 nm。4周内，纳米粒粒径未见显著变化。结论 MePEG-PHDCA和PHDCA合成成功。制备的纳米粒在水溶液中不易发生显著聚集、整体溶蚀或表面溶蚀降解，纳米粒稳定性较好。     

Long-Circulating PEGylated Polycyanoacrylate Nanoparticles as New Drug Carrier for Brain Delivery

Purpose. The aim of this study was to evaluate the ability of long-circulating PEGylated cyanoacrylate nanoparticles to diffuse into the brain tissue. Methods. Biodistribution profiles and brain concentrations of [¹⁴C]-radiolabeled PEG-PHDCA, polysorbate 80 or poloxamine 908-coated PHDCA nanoparticles, and uncoated PHDCA nanoparticles were determined by radioactivity counting after intravenous administration in mice and rats. In addition, the integrity of the blood-brain barrier (BBB) after nanoparticles administration was evaluated by in vivo quantification of the diffusion of [¹⁴C]-sucrose into the brain. The location of fluorescent nanoparticles in the brain was also investigated by epi-fluorescent microscopy. Results. Based on their long-circulating characteristics, PEGylated PHDCA nanoparticles penetrated into the brain to a larger extent than all the other tested formulations. Particles were localized in the ependymal cells of the choroid plexuses, in the epithelial cells of pia mater and ventricles, and to a lower extent in the capillary endothelial cells of BBB. These phenomena occurred without any modification of BBB permeability whereas polysorbate 80-coated nanoparticles owed, in part, their efficacy to BBB permeabilization induced by the surfactant. Poloxamine 908-coated nanoparticles failed to increase brain concentration probably because of their inability to interact with cells. Conclusions. This study proposes PEGylated poly (cyanoacrylate) nanoparticles as a new brain delivery system and highlights two requirements to design adequate delivery systems for such a purpose: a) long-circulating properties of the carrier, and b) appropriate surface characteristics to allow interactions with BBB endothelial cells.     

Pegylated Nanoparticles from a Novel Methoxypolyethylene Glycol Cyanoacrylate-Hexadecyl Cyanoacrylate Amphiphilic Copolymer

Purpose. The aim of this work was to develop PEGylated poly(alkylcyanoacrylate) nanoparticles from a novel methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate copolymer. Methods. PEGylated and non-PEGylated nanoparticles were formed by nanoprecipitation or by emulsion/solvent evaporation. Nanoparticles size, zeta potential and surface hydrophobicity were investigated. Surface chemical composition was determined by X-ray photoelectron spectroscopy. Nanoparticle morphology was investigated by transmission electron microscopy after freeze-fracture. Nanoparticles cytotoxicity was assayed in vitro, onto mouse peritoneal macrophages. Cell viability was determined through cell mitochondrial activity, by a tetrazolium-based colorimetric method (MTT test). Finally, the degradation of PEGylated and non-PEGylated poly(hexadecyl cyanoacrylate) nanoparticles was followed spectrophotometrically during incubation of nanoparticles in fetal calf serum. Results. Monodisperse nanoparticles with a mean diameter ranging between 100 and 200 nm were obtained using nanoprecipitation or emulsion/solvent evaporation as preparation procedures. A complete physico-chemical characterization, including surface chemical analysis, allowed to confirm the formation of PEG-coated nanoparticles. The PEGylation of the cyanoacrylate polymer showed reduced cytotoxicity towards mouse peritoneal macrophages. Furthermore, the presence of the PEG segment increased the degradability of the poly(hexadecyl cyanoacrylate) polymer in presence of calf serum. Conclusions. We succeeded to prepare PEGylated nanoparticles from a novel poly(methoxypolyethyleneglycol cyanoacrylate-co-hexadecyl cyanoacrylate) by two different techniques. Physico-chemical characterization showed the formation of a PEG coating layer. Low cytoxicity and enhanced degradation were also shown.     

Body distribution and in situ evading of phagocytic uptake by macrophages of long-circulating poly （ethylene glycol） cyanoacrylate-co-nhexadecyl cyanoacrylate nanoparticles

AIM: To investigate the body distribution in mice of [14C]-labeled poly methoxyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate (PEG-PHDCA) nanoparticles and in situ evading of phagocytic uptake by mouse peritoneal macrophages. METHODS: PEG-PHDCA copolymers were synthesized by condensation of methoxypolyethylene glycol cyanoacetate with [14C]-hexadecyl-cyanoacetate. [14C]-nanoparticles were prepared using the nanoprecipitation/solvent diffusion method, while fluorescent nanoparticles were prepared by incorporating rhodamine B. In situ phagocytic uptake was evaluated by flow cytometry. Body distribution in mice was evaluated by determining radioactivity in tissues using a scintillation method. RESULTS: Phagocytic uptake by macrophages can be efficiently evaded by fluorescent PEG-PHDCA nanoparticles. After 48 h, 31% of the radioactivity of the stealth [14C]-PEG-PHDCA nanoparticles after iv injection was still found in blood, whereas non-stealth PHDCA nanoparticles were cleaned up from the bloodstream in a short time. The distribution of stealth PEG-PHDCA nanoparticles and non-stealth PHDCA nanoparticals in mice was poor in lung, kidney, and brain, and a little higher in hearts. Lymphatic accumulation was unusually high for both stealth and non-stealth nanoparticles, typical of lymphatic capture. The accumulation of stealth PEG-PHDCA nanoparticles in the spleen was 1.7 times as much as that of non-stealth PHDCA (P< 0.01). But the accumulation of stealth PEG-PHDCA nanoparticles in the liver was 0.8 times as much as that of non-stealth PHDCA (P< 0.05). CONCLUSION: PEGylation leads to long-circulation of nanoparticles in the bloodstream, and splenotropic accumulation opens up the potential for further development of spleen-targeted drug delivery.     

Stealth polycyanoacrylate nanoparticles as tumor necrosis factor-alpha carriers: pharmacokinetics and anti-tumor effects.

The objective of this study was to investigate the pharmacokinetics and in vivo anti-tumor effect of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) encapsulated in poly(methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles. Our experimental results showed that PEG-PHDCA nanoparticles could extend the half-life of rHuTNF-alpha to 7.42 h and obviously change the protein biodistribution in tissues, and in particular, increase accumulation of rHuTNF-alpha in tumor. Compared with PHDCA nanoparticles and free rHuTNF-alpha, PEG-PHDCA nanoparticles loaded with rHuTNF-alpha showed higher antitumor potency at the same dose, which might be related to its higher accumulation in tumor tissues and longer plasma circulation time. Therefore, PEG-PHDCA nanoparticles could be an effective carrier for rHuTNF-alpha.     

Design,physicochemical characterisation,and in vitro cytotoxicity of cisplatin-loaded PEGylated chitosan injectable nano / sub-micron crystals

The study aimed to develop cisplatin-loaded PEGylated chitosan nanoparticles. The optimal batch of cisplatin-loaded PEGylated chitosan nanoparticles had a + 49.9 mV zeta potential, PDI of 0.347, and % PDI of 58.9. Nanoparticle zeta size was 741.4 z. d.nm, the size in diameter was 866.7 ± 470.5 nm, and nanoparticle conductivity in colloidal solution was 0.739 mS/cm. Differential scanning calorimetry (DSC) revealed that cisplatin-loaded PEGylated chitosan nanoparticles had sharp endothermic peaks at temperatures at 168.6 °C. The thermogravimetric analysis (TGA) showed the weight loss of cisplatin-loaded PEGylated chitosan nanoparticles, which was observed as 95% at 262.76 °C. XRD investigation on cisplatin-loaded PEGylated chitosan nanoparticles exhibited distinct peaks at 2θ as 9.7°, 20.4°, 22.1°, 25.3°, 36.1°, 38.1°, 39.5°, 44.3°, and 64.5°, confirming crystalline structure. The ¹H NMR analysis showed the fingerprint region of cisplatin-loaded PEGylated chitosan nanoparticles as 0.85, 1.73, and 1.00 ppm in the proton dimension and de-shielded proton peaks appeared at 3.57, 3.58, 3.58, 3.59, 3.65, 3.67, 3,67, 3,67, 3.70, 3.71, 3.77, 3.78 and 4.71 ppm. The ¹³C NMR spectrum showed specified peaks at 63.18, 69.20, and 70.77 ppm. The FT-IR spectra of cisplatin loaded PEGylated nanoparticles show the existence of many fingerprint regions at 3186.52, 2931.68, 1453.19, 1333.98, 1253.71, 1085.19, 1019.60, 969.98, 929.53, 888.80, 706.13, and 623.67 cm⁻¹. The drug release kinetics of cisplatin loaded PEGylated chitosan nanoparticles showed zero order kinetics with 48% of drug release linearity fashion which has R² value of 0.9778. Studies on the MCF-7 ATCC human breast cancer cell line in vitro revealed that the IC50 value 82.08 µg /mL. Injectable nanoparticles had good physicochemical and cytotoxic properties. This method is novel since the application of the PEGylation processes leads to an increased solubility of chitosan nanoparticles at near neutral pH.     

Nanoparticles Based on a Hydrophilic Polyester with a Sheddable PEG Coating for Protein Delivery

Purpose

To investigate the effect of polyethylene glycol (PEG) in nanoparticles based on blends of hydroxylated aliphatic polyester, poly(D,L-lactic-co-glycolic-co-hydroxymethyl glycolic acid) (PLGHMGA) and PEG-PLGHMGA block copolymers on their degradation and release behavior.

Methods

Protein-loaded nanoparticles were prepared with blends of varying ratios of PEG-PLGHMGA (molecular weight of PEG 2,000 and 5,000 Da) and PLGHMGA, by a double emulsion method with or without using poly(vinyl alcohol) (PVA) as surfactant. Bovine serum albumin and lysozyme were used as model proteins.

Results

PEGylated particles prepared without PVA had a zeta potential ranging from ~ ?3 to ~?35 mV and size ranging from ~200 to ~600 nm that were significantly dependent on the content and type of PEG-block copolymer. The encapsulation efficiency of the two proteins however was very low (<30%) and the particles rapidly released their content in a few days. In contrast, all formulations prepared with PVA showed almost similar particle properties (size: ~250 nm, zeta potential: ~?1 mV), while loading efficiency for both model proteins was rather high (80–90%). Unexpectedly, independent of the type of formulation, the nanoparticles had nearly the same release and degradation characteristics. NMR analysis showed almost a complete removal of PEG in 5 days which explains these marginal differences.

Conclusions

Protein release and particle degradation are not substantially influenced by the content of PEG, likely because of the fast shedding of the PEG blocks. These PEG shedding particles are interesting system for intracellular delivery of drugs.     

Design of naltrexone-loaded hydrolyzable crosslinked nanoparticles

A hydrolyzable crosslinker (N,O-dimethacryloylhydroxylamine (MANHOMA)) was synthesized by a modified method and was characterized using 1H-NMR, FTIR, and melting point determination. Naltrexone-loaded nanoparticles were prepared by copolymerization of poly(ethylene glycol)1000 monomethyl ether mono methacrylate (PEO-MA), methyl methacrylate (MMA) and N,O-dimethacryloylhydroxylamine (MANHOMA) in 0.4% poly(vinyl alcohol) aqueous solution. The nanoparticles were characterized by FTIR, particle size determination and transmission electron microscope (TEM). The TEM photomicrographs of the nanoparticles show a crosslinked core surrounded by a ring formed by the polyethylene glycol tail of PEO-MA. The loading efficiency of the nanoparticles and in vitro drug availability from the nanoparticles were investigated. The naltrexone-loaded hydrolyzable crosslinked nanoparticles were able to sustain the release of naltrexone for different periods of time, depending on the monomer feed composition.     

Increasing entrapment of peptides within poly(alkyl cyanoacrylate) nanoparticles prepared from water-in-oil microemulsions by copolymerization

Low molecular hydrophilic actives such as peptides are typically poorly encapsulated within poly(alkyl cyanoacrylate) nanoparticles when prepared from micellar or microemulsion templates. The aim of the present study was to investigate whether the entrapment of peptides within poly(alkyl cyanoacrylate) nanoparticles could be increased by functionalizing the peptide so that it could copolymerize with the alkyl cyanoacrylate monomer. Peptide and acryloyl functionalized peptide representing the antigenic epitope of the lymphocytic choriomeningitis virus glycoprotein (LCMV(33-41)) were synthesized using solid-phase peptide synthesis. Poly(alkyl cyanoacrylate) nanoparticles were prepared to encapsulate either peptide or functionalized peptide using both an aqueous micellar and a water-in-oil microemulsion polymerization template. Using the micellar template, nanoparticles could not be produced in the presence of acryloyl peptide. Rather an agglomerated mass formed on the stirrer. In contrast, nanoparticles could be prepared using both acryloyl and parent peptide using the water-in-oil microemulsion template. Encapsulation efficiency was more than twofold greater for functionalized peptide, being greater than 90%. Encapsulation efficiency of functionalized peptide was also observed to increase with increasing the amount of alkyl cyanoacrylate monomer used for polymerization. A biphasic release profile was observed for the nanoparticles entrapping the non-functionalized peptide with greater than 50% of peptide being released during the first 10min and with around 90% being released at 6h. In contrast, less than 10% of the total amount of acryloyl LCMV(33-41) entrapped within the nanoparticles was detected in the release media following the initial 10min, and no further release of peptide was observed up to the termination of the release study at 360min. The difference in entrapment and release kinetics between the parent and functionalized peptide strongly supports the presumption that most of the acryloyl peptide actually intervened in the copolymerization with alkyl cyanoacrylate monomer and was covalently bound within the nanoparticles instead of being physically entrapped or adsorbed which appeared to be the case for the parent peptide. Thus, functionalizing a peptide so that it can copolymerize with the alkyl cyanoacrylate monomer is a strategy which can be used to increase the entrapment efficiency of peptides within poly(alkyl cyanoacrylate) nanoparticles and also maintain the peptide associated with nanoparticles so that the benefits of nanoparticulate delivery can be exploited.     

Effect of MePEG molecular weight and particle size on in vitro release of tumor necrosis factor-α-loaded nanoparticles

Aim: To study the in vitro release of recombinant human tumor necrosis factoralpha (rHuTNF-α) encapsulated in poly (methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles, and investigate the influence of methoxypolyethyleneglycol (MePEG) molecular weight and particle size. Methods: Three sizes (approximately 80, 170, and 240 nm) of PEGPHDCA nanoparticles loading rHuTNF-α were prepared at different MePEG molecular weights (Mr =2000, 5000, and 10 000) using the double emulsion method. The in vitro rHuTNF-α release was studied in PBS and rat plasma. Results: A higher burst-release and cumulative-release rate were observed for nanoparticles with higher MePEG molecular weight or smaller particle size. A decreased cumulative release of rHuTNF-α following the initial burst effect was found in PBS, while the particle sizes remained constant and MePEG liberated. In contrast, in rat plasma, slowly increased cumulative-release profiles were obtained after the burst effect. During a 5-h incubation in rat plasma, more than 50% of the PEGPHDCA nanoparticles degraded. Conclusion: The MePEG molecular weight and particle size had an obvious influence on rHuTNF-α release, rHuTNF-α released from PEG-PHDCA nanoparticles in a diffusion-based pattern in PBS, but in a diffusion and erosion-controlled manner in rat plasma.