Co-delivery honokiol and doxorubicin in MPEG-PLA nanoparticles.

The combination chemotherapy is an important protocol in cancer therapy. Honokiol shows synergistic anticancer effect with doxorubicin. In this paper, honokiol and doxorubicin co-loaded MPEG-PLA nanoparticles were prepared. The particle size, morphology, in vitro release profile, cytotoxicity and cell proliferation study were studied in detail. The results indicated that honokiol and doxorubicin could be efficiently loaded into MPEG-PLA nanoparticles simultaneously, and could be released out in an extended period in vitro. Meanwhile, honokiol and doxorubicin in MPEG-PLA nanoparticle could efficiently suppress cancer cell proliferation in vitro. The described honokiol and doxorubicin co-loaded MPEG-PLA nanoparticle might be a novel anticancer agent.

A 12-month prospective survey of perinatal outcome of liveborn neonates in Julu County, China.

BACKGROUND: Population based epidemiologic study on the main diseases and birth status of liveborn neonates remains scarce in China, especially in rural areas where a large number of neonates are born. The aim of this study was to establish an epidemiological basis of live births in Julu County, a representative of the northern and mid-western parts of China in terms of demography, disease pattern and women and children's health care infrastructure. METHODS: The perinatal data of all live births were prospectively collected in three participating county-level hospitals from September 1, 2007 to August 30, 2008. RESULTS: There were 5822 live births in these hospitals. Among all live births, 53.7% were male and 4.5% were born prematurely. Mean (SD) birth weight (BW) was (3348 ± 503) g. The low (< 2500 g) and very low BW (< 1500 g) infants accounted for 3.8% and 0.5% of the total births, with 6.5% as small for gestational age and 2.8% as multi-births. Cesarean section rate was 30.2%, of which 68.6% were elective. There were 745 infants (12.8% of the live births) admitted to local neonatal wards within 7 days of postnatal life, in which 48.3% and 19.3% were due to perinatal asphyxia and prematurity, respectively. The incidences of perinatal aspiration syndrome, transient tachypnea and respiratory distress syndrome were 4.9%, 0.6% and 0.5%, respectively. Neonatal mortality was 7.6‰ (44/5822), with 16 in delivery room and 28 in neonatal ward before discharge. CONCLUSIONS: This study provided a population-based perinatal data of live births and neonatal mortality in a northern China county with limited resources. Neonatal disorders related to perinatal asphyxia remain a serious clinical problem, which calls for sustained education of advanced neonatal resuscitation and improvement in the quality of perinatal-neonatal care.

A novel transdermal honokiol formulation based on Pluronic F127 copolymer.

This paper developed a new hydrophobic honokiol transdermal delivery system. First, Honokiol was loaded into Pluronic F127 micelles by direct dissolution method assisted by ultrasound. Then the obtained honokiol-loaded F127 micelles were incorporated into thermosensitive F127 hydrogel, which made the composite system bioadhesive. The particle size, drug loading, and encapsulation efficiency were determined. The sol-gel transitions of the copolymer, honokiol release profile in vitro, and the permeation studies in vitro were studied in detail. The lower critical solution temperature (LCST) of the composite system decreases with increase in the mass of honokiol in the system. Honokiol could be sustained released from the system in vitro. In in vitro permeation studies, honokiol could be absorbed per cutem. The described drug delivery system might have great potential application for transdermal delivery of hydrophobic drugs such as honokiol.

Preparation of MPEG-PLA nanoparticle for honokiol delivery in vitro.

Honokiol (HK) shows potential application in cancer treatment, but its poor water solubility restricts clinical application greatly. In this paper, monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) was synthesized by ring-opening polymerization and processed into nanoparticle for honokiol delivery. Chemical structure of the synthesized polymer was confirmed by (1)H NMR, and its molecular weight was determined by gel permeation chromatography (GPC). Honokiol loaded MPEG-PLA nanoparticles were prepared by solvent extract method. And particle size distribution, morphology, drug loading, drug release profile and anticancer activity in vitro were studied in detail. The described honokiol loaded MPEG-PLA nanoparticles in this paper might be a novel formulation for honokiol delivery.

A novel composite drug delivery system: honokiol nanoparticles in thermosensitive hydrogel based on chitosan.

In this article, a novel composite drug delivery system, honokiol nanoparticles in biodegradable hydrogels based on chitosan (CS) and beta-glycerophosphate (beta-GP), was prepared. CS/beta-GP solution was liquid at room temperature and turned into gel as temperature increased. With increase in beta-GP concentration, the sol-gel transition temperature decreased accordingly. Honokiol nanoparticles with diameter of about 30 nm were prepared by emulsion solvent evaporation method. The sol-gel transition temperature of CS/beta-GP system decreased as F-127 presented in honokiol nanoparticles. In vitro release profiles were studied, the results showed that honokiol could be slowly released from CS/beta-GP gel over at least 2 weeks and the release rate was greatly influenced by initial drug loading. The described injectable hydrogels based on chitosan (CS) and beta-glycerophosphate (beta-GP) might have potential application as local drug delivery for honokiol.

Chitosan-alginate sponge: preparation and application in curcumin delivery for dermal wound healing in rat.

A biodegradable sponge, composed of chitosan (CS) and sodium alginate (SA), was successfully obtained in this work. The sponge was ethereal and pliable. The chemical structure and morphology of the sponges was characterized by FTIR and SEM. The swelling ability, in vitro drug release and degradation behaviors, and an in vivo animal test were employed to confirm the applicability of this sponge as a wound dressing material. As the chitosan content in the sponge decreased, the swelling ability decreased. All types of the sponges exhibited biodegradable properties. The release of curcumin from the sponges could be controlled by the crosslinking degree. Curcumin could be released from the sponges in an extended period for up to 20 days. An in vivo animal test using SD rat showed that sponge had better effect than cotton gauze, and adding curcumin into the sponge enhanced the therapeutic healing effect.

Preparation and characterization of vitamin-12 loaded biodegradable pH-sensitive microgels.

This paper prepared novel biodegradable and pH-sensitive microgels based on Poly(epsilon-caprolactone)-Pluronic-Poly(epsilon-caprolactone)-dimethacrylate (PCFC-DMA), Poly(ethylene glycol) dimethacrylate (PEG-DMA) and methylacrylic acid (MAA) cross-linked with N,N'-methylenebisacrylamide (BIS), initiated by NaHSO(3), K(2)S(2)O(8). The blank microgels were prepared by inversed-phase suspension polymerization method and pH sensitivity of microgels was characterized. Then the blank microgels were loaded with hydrophilic model drug vitamin-12 (VB-12) and in vitro drug release behaviour was also studied here.

Poly(epsilon-caprolactone)/poly(ethylene glycol)/poly(epsilon-caprolactone) nanoparticles: preparation, characterization, and application in doxorubicin delivery.

Biodegradable poly(epsilon-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer nanoparticles showed potential application in drug delivery systems. In this article, monodisperse poly(epsilon-caprolactone)/poly(ethylene glycol)/poly(epsilon-caprolactone) (PCL/PEG/PCL, PCEC) nanoparticles, approximately 40 nm, were prepared by solvent extraction method using acetone as the organic solvent. These PCL/PEG/PCL nanoparticles did not induce hemolysis in vitro and did not show toxicity in vitro or in vivo. The prepared PCL/PEG/PCL nanoparticles were employed to load doxorubicin by a pH-induced self-assembly method. In vitro release study indicated that doxorubicin release from nanoparticles at pH 5.5 was faster than that at pH 7.0. The encapsulation of doxorubicin in PCL/PEG/PCL nanoparticles enhanced the cytotoxicity of doxorubicin on a C-26 cell line in vitro. Meanwhile, compared with free doxorubicin, doxorubicin in nanoparticles could more efficiently treat mice bearing subcutaneous C-26 tumors. The doxorubicin-loaded PCL/PEG/PCL nanoparticles might be a novel doxorubicin formulation for cancer therapy.

Self-assembled hydrophobic honokiol loaded MPEG-PCL diblock copolymer micelles.

PURPOSE: Honokiol showed potential application in cancer treatment, but its poor water solubility restricts its clinical application greatly. So, we designed a self-assembled monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone) (MPEG-PCL) micelle to load honokiol to overcome its poor water solubility. METHODS: We synthesized MPEG-PCL diblock copolymer that could self-assemble into monodisperse micelles at the particle size of ca.18 nm in water. Honokiol was loaded into MPEG-PCL micelle by direct dissolution method assisted by ultrasound, without any surfactants, organic solvents, and vigorous stirring. RESULTS: The blank MPEG-PCL micelles (100 mg/mL) did not induce any hemolysis in vitro and showed very low toxicity ex vivo and in vivo. Honokiol could be molecularly incorporated into MPEG-PCL micelles at the drug loading of about 20% by direct dissolution method assisted by ultrasound. After loaded into MPEG-PCL micelles, honokiol maintained its molecular structure and anticancer activity in vitro. Honokiol could be sustained released from MPEG-PCL micelles in vitro. The honokiol loaded MPEG-PCL micelles could be lyophilized without any adjuvant. CONCLUSION: The prepared honokiol formulation based on self-assembled MPEG-PCL micelle was stable, safe, effective, easy to produce and scale up, and showed potential clinical application.

Preparation of honokiol-loaded chitosan microparticles via spray-drying method intended for pulmonary delivery.

It has been demonstrated that spray-drying is a powerful method to prepare dry powders for pulmonary delivery. This paper prepared dispersible dry powders based on chitosan and mannitol containing honokiol nanoparticles as model drug. The results showed that the prepared microparticles are almost spherical and have appropriate aerodynamic properties for pulmonary delivery (aerodynamic diameters was between 2.8-3.3 microm and tapped density ranging from 0.14-0. 18 g/cm(3)). Moreover, surface morphology and aerodynamic properties of the powders were strongly affected by the content of mannitol. Fourier transform infra-red (FTIR) spectrum of powders indicated that the honokiol nanoparticles were successfully incorporated into microparticles. In vitro drug release profile was also observed. The content of mannitol in powders significantly influenced the release rate of honokiol from matrices.

Poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) nanoparticles for honokiol delivery in vitro.

In this article, poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanoparticles were successfully prepared for honokiol delivery in vitro. Blank or honokiol loaded PCL-PEG-PCL nanoparticles were prepared in moderate condition by solvent diffusion method without using any surfactants. The prepared blank PCL-PEG-PCL nanoparticles are mono-dispersed and smaller than 200 nm. The particle size increased with increase in polymer concentration and oil-water (O/W) ratio. The prepared PCL-PEG-PCL nanoparticles (40 mg/mL, ca. 106 nm) did not induce hemolysis in vitro. And the 50% inhibiting concentration (IC50) of it (48 h) on HEK293 cells was higher than 5 mg/mL. Honokiol could be efficiently loaded into PCL-PEG-PCL nanoparticles and released from these nanoparticles in an extended period in vitro. After honokiol (HK) was entrapped into PCL-PEG-PCL nanoparticles, the particle size increased with the increase in HK/PCEC mass ratio in feed, and the encapsulated honokiol retained potent anticancer activity in vitro. The PCL-PEG-PCL nanoparticle was suitable for honokiol delivery, and such honokiol loaded PCL-PEG-PCL nanoparticle was a novel honokiol formulation.

Self-assembled honokiol-loaded micelles based on poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) copolymer.

Self-assembled polymeric micelles are widely applied in drug delivery system (DDS). In this study, honokiol (HK) loaded micelles were prepared from biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) copolymers. Micelles were prepared by self-assembly of triblock copolymer PCEC in distilled water triggered by its amphiphilic character without any organic solvent. Drug loading and encapsulation efficiency were determined by adjusting the weight ratio of HK and PCEC. The particle size and zeta potential distribution of obtained micelles were determined using Malvern laser particle sizer, and spherical geometry were observed on atomic force microscope (AFM). Otherwise, the thermo-sensitivity of honokiol-loaded micelles was monitored. And the cytotoxicity results of drug loaded micelles showed that the encapsulated honokiol remained potent antitumor effect. Moreover, in vitro release profile demonstrated a significant difference between rapid release of free honokiol and much slower and sustained release of HK-loaded micelles. These results suggested that we have successfully prepared honokiol-loaded micelles in an improved method which is safer and more efficient. The prepared micelles might be potential carriers for honokiol delivery in cancer chemotherapy.

Preparation of alginate coated chitosan microparticles for vaccine delivery.

BACKGROUND: Absorption of antigens onto chitosan microparticles via electrostatic interaction is a common and relatively mild process suitable for mucosal vaccine. In order to increase the stability of antigens and prevent an immediate desorption of antigens from chitosan carriers in gastrointestinal tract, coating onto BSA loaded chitosan microparticles with sodium alginate was performed by layer-by-layer technology to meet the requirement of mucosal vaccine. RESULTS: The prepared alginate coated BSA loaded chitosan microparticles had loading efficiency (LE) of 60% and loading capacity (LC) of 6% with mean diameter of about 1 mum. When the weight ratio of alginate/chitosan microparticles was greater than 2, the stable system could be obtained. The rapid charge inversion of BSA loaded chitosan microparticles (from +27 mv to -27.8 mv) was observed during the coating procedure which indicated the presence of alginate layer on the chitosan microparticles surfaces. According to the results obtained by scanning electron microscopy (SEM), the core-shell structure of BSA loaded chitosan microparticles was observed. Meanwhile, in vitro release study indicated that the initial burst release of BSA from alginate coated chitosan microparticles was lower than that observed from uncoated chitosan microparticles (40% in 8 h vs. about 84% in 0.5 h). SDS-polyacrylamide gel electrophoresis (SDS-PAGE) assay showed that alginate coating onto chitosan microparticles could effectively protect the BSA from degradation or hydrolysis in acidic condition for at least 2 h. The structural integrity of alginate modified chitosan microparticles incubated in PBS for 24 h was investigated by FTIR. CONCLUSION: The prepared alginate coated chitosan microparticles, with mean diameter of about 1 mum, was suitable for oral mucosal vaccine. Moreover, alginate coating onto the surface of chitosan microparticles could modulate the release behavior of BSA from alginate coated chitosan microparticles and could effectively protect model protein (BSA) from degradation in acidic medium in vitro for at least 2 h. In all, the prepared alginate coated chitosan microparticles might be an effective vehicle for oral administration of antigens.