Acceptable deviation of labial tubercle and anterior tooth midlines relative to facial midline in smile aesthetics: A retrospective observational study.

Smile aesthetics are mainly influenced by the relative position of facial midline (FC-line), anterior tooth midline (AT-line) and labial tubercle midline (LT-line). However, the acceptable deviation of LT-line and AT-line relative to FC-line is unknown. This study aims to fill the critical gap. We adopted the method of cross-sectional study, the frontal full-face smile photographs of 1 subject set (1 male) were enrolled. Taking the FC-line as the center line, twelve images with 1-mm increment relative to FC-line (right or left deviation, the maximum deviation distance was 3-mm) in LT-line deviation model or LT + AT-line deviation model (LT-line coincided with AT-line basing on LT-line deviation model) were produced. Basing on Q-sort assessment, the images were evaluated by 160 dentists, 165 orthodontic patients and 163 freshmen. And the collected Q-sort scores were subjected to nonparametric comparative analysis using SPSS 18.0. There were significant differences in Q-sort scores among different groups (P < .01). When the deviation distance was 1 mm in dentist and orthodontic patient or 2 mm in freshman group, there was no significant difference in smile attractiveness scores between the LT line deviation model and the LT + AT line deviation model (P > .05). We also found that the score of male dentist significantly higher than female dentist (P < .05). However, the scores of right deviation in dentists and orthodontic patients were significantly lower than those in left deviation (P < .05). The acceptable deviation of LT-line and AT-line relative to FC-line should be kept within 2 mm. Besides, raters' occupation and gender, and deviation direction of model may influence the smile aesthetics.

Preparation of core cross-linked PCL-PEG-PCL micelles for doxorubicin delivery in vitro.

Doxorubicin has been widely used in cancer treatment, but its severe side-effects restrict its clinical application greatly. So, we hope to design a novel delivery system to decrease its side-effects. In this paper, we prepared core cross-linked micelle based on poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (CCPCEC) at about 30 nm in diameter with a narrow distribution. The prepared core cross-linked PCL-PEG-PCL micelles were employed to load doxorubicin by pH-induced self-assembly method. Doxorubicin-loading did not obviously affect the micelle size or size distribution. Furthermore, these micelles exhibited a significantly enhanced thermodynamic stability against dilution with aqueous solvents and showed CMC in the range of 1 x 10(-3) to 2 x 10(-3) mg/mL. Cytotoxicity study confirmed great biocompatibility of the micelles and showed that the encapsulated doxorubicin in CCPCEC micelles enhanced the cytotoxicity of doxorubicin on C26 cell line in vitro. Moreover, in vitro release profile demonstrated a significant difference between rapid release of free doxorubicin and much slower and sustained release of doxorubicin-loaded core cross-linked micelles. In addition, a faster DOX-release from micelles at pH 5.5 than that at pH 7.4 was also observed. These results suggested that this new biodegradable Core Cross-linked PCL-PEG-PCL Micelles might be potential carriers for drug delivery in cancer chemotherapy.

Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic honokiol delivery: I. Preparation and characterization.

This study aims to develop self-assembled poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles to encapsulate hydrophobic honokiol (HK) in order to overcome its poor water solubility and to meet the requirement of intravenous administration. Honokiol loaded micelles (HK-micelles) were prepared by self-assembly of PECE copolymer in aqueous solution, triggered by its amphiphilic characteristic assisted by ultrasonication without any organic solvents, surfactants and vigorous stirring. The particle size of the prepared HK-micelles measured by Malvern laser particle size analyzer were 58 nm, which is small enough to be a candidate for an intravenous drug delivery system. Furthermore, the HK-micelles could be lyophilized into powder without any adjuvant, and the re-dissolved HK-micelles are stable and homogeneous with particle size about 61 nm. Furthermore, the in vitro release profile showed a significant difference between the rapid release of free HK and the much slower and sustained release of HK-micelles. Moreover, the cytotoxicity results of blank micelles and HK-micelles showed that the PECE micelle was a safe carrier and the encapsulated HK retained its potent antitumor effect. In short, the HK-micelles were successfully prepared by an improved method and might be promising carriers for intravenous delivery of HK in cancer chemotherapy, being effective, stable, safe (organic solvent and surfactant free), and easy to produce and scale up.

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 novel poly(epsilon-caprolactone)-pluronic-poly(epsilon-caprolactone) grafted polyethyleneimine(PCFC-g-PEI), Part 1, synthesis, cytotoxicity, and in vitro transfection study.

BACKGROUND: Polyethyleneimine (PEI), a cationic polymer, is one of the successful and widely used vectors for non-viral gene transfection in vitro. However, its in vivo application was greatly limited due to its high cytotoxicity and short duration of gene expression. To improve its biocompatibility and transfection efficiency, PEI has been modified with PEG, folic acid, and chloroquine in order to improve biocompatibility and enhance targeting. RESULTS: Poly(epsilon-caprolactone)-Pluronic-Poly(epsilon-caprolactone) (PCFC) was synthesized by ring-opening polymerization, and PCFC-g-PEI was obtained by Michael addition reaction with GMA-PCFC-GMA and polyethyleneimine (PEI, 25 kD). The prepared PCFC-g-PEI was characterized by 1H-NMR, SEC-MALLS. Meanwhile, DNA condensation, DNase I protection, the particle size and zeta potential of PCFC-g-PEI/DNA complexes were also determined. According to the results of flow cytometry and MTT assay, the synthesized PCFC-g-PEI, with considerable transfection efficiency, had obviously lower cytotoxicity against 293 T and A549 cell lines compared with that of PEI 25 kD. CONCLUSION: The cytotoxicity and in vitro transfection study indicated that PCFC-g-PEI copolymer prepared in this paper was a novel gene delivery system with lower cytotoxicity and considerable transfection efficiency compared with commercial PEI (25 kD).

Novel composite drug delivery system for honokiol delivery: self-assembled poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) micelles in thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) hydrogel.

This study aims to develop a novel composite drug delivery system (CDDS) for hydrophobic honokiol delivery: honokiol loaded micelles in thermosensitive hydrogel (honokiol micelles/hydrogel) based on biodegradable poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers. In our work, we found that PECE copolymers with different molecular weight and PEG/PCL ratios could be administered to form micelles or thermosensitive hydrogel, respectively. Honokiol loaded PECE micelles (honokiol micelles) were prepared by self-assembly of biodegradable PECE copolymer (PEG5000-PCL5000-PEG5000) triggered by its amphiphilic characteristic assisted by ultrasonication without using any organic solvents and surfactants. Meanwhile, biodegradable and injectable thermosensitive PECE hydrogel (PEG550-PCL2400-PEG550) with a lower sol-gel transition temperature at around physiological temperature was also prepared successfully. Furthermore, the obtained honokiol micelles/hydrogel CDDS was a free-flowing sol at ambient temperature and became a nonflowing gel at body temperature. The cytotoxicity results showed that the CDDS was a safe carrier and the encapsulated honokiol retained its potent antitumor effect. In addition, the in vitro release profile demonstrated a significant difference between rapid release of free honokiol and much slower and sustained release of honokiol micelles/hydrogel. The results suggested that the CDDS might have great potential applications in cancer chemotherapy.

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.

Synthesis and characterization of the paclitaxel/MPEG-PLA block copolymer conjugate.

A paclitaxel/MPEG-PLA block copolymer conjugate was prepared in three steps: (1) hydroxyl-terminated diblock copolymer of monomethoxy-poly(ethylene glycol)-b-poly(lactide) (MPEG-PLA) was synthesized by ring-opening polymerization of L-lactide using MPEG as a maroinitiator; (2) it was converted to carboxyl-terminated MPEG-PLA by reacting with mono-t-butyl ester of diglycolic acid and subsequent deprotecting the t-butyl group with TFA; (3) the latter was reacted with paclitaxel in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. Structures of the polymers synthesized were confirmed by (1)H NMR, and their molecular weights were determined by gel permeation chromatography. The antitumor activity of the conjugate against human liver cancer H7402 cells was evaluated by MTT method. The results showed that paclitaxel can be released from the conjugate without losing cytotoxicity.

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.

Polymeric matrix for drug delivery: honokiol-loaded PCL-PEG-PCL nanoparticles in PEG-PCL-PEG thermosensitive hydrogel.

In this article, we demonstrated a novel injectable polymer matrix: honokiol (HK) loaded poly (epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanoparticles in thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel for the drug local delivery. First, HK, as a model hydrophobic drug, was loaded into PCL-PEG-PCL nanoparticles by emulsion solvent evaporation method to overcome its poor water solubility. Then, the HK-loaded PCEC nanoparticles (HK-PCEC) were incorporated into thermosensitive PEG-PCL-PEG hydrogel, which was sol at low temperature and could gel as a depot for sustained release of drug in situ after topical injection. The HK-PCEC incorporated PECE hydrogel (HK-PCEC-PECE) was biodegradable and could be gradually eliminated from the injection site in about 2 weeks after subcutaneously injected into mice. The in vitro release studies indicated that HK could be released from HK-PCEC and HK-PCEC-PECE in a sustained manner. Such biodegradable smart drug-delivery system might have great potential application in injectable hydrophobic drug local delivery system.

Safety evaluation of amphiphilic three-armed star-shaped copolymer micelles.

In our previous work, we had prepared a biodegradable amphiphilic three-armed star-shaped copolymers (SPCE) based on poly(epsilon-caprolactone) (PCL) and poly(ethylene glycol) (PEG), which could form micelles by self-assembly method and it was a potential carrier for hydrophobic drug. For further application, the safety of SPCE micelles was evaluated in vitro and in vivo here. (13)C-NMR was used to confirm the formation of the micelles in aqueous solution, and the morphology was observed on transmission electron microscope (TEM). Also, thermostability of blank SPCE micelles was determined by Malvern Nano-ZS 90 laser particle size analyzer. In vitro toxicity evaluation included hemolytic test and cytotoxicity. In vivo acute toxicity tests and histopathological study of SPCE micelles were carried out on BALB/C mice which were administrated SPCE micelles (1 g/kg b.w.) intravenously. In acute toxicity test, the mice were observed continuously for 7 days, obtained their body weight every day, at last the mice was sacrificed for the following study: the blood of the mice was assigned for blood chemistry and routine analysis, the heart, liver, spleen, lung, and kidneys were used for histopathological study. All results indicated that the biodegradable self-assembled SPCE micelles were nontoxic; therefore, it might be used as a safe candidate for drug delivery system.

Enhanced gene delivery using biodegradable poly(ester amine)s (PEAs) based on low-molecular-weight polyethylenimine and poly(epsilon-caprolactone)-pluronic-poly(epsilon-caprolactone).

In this paper, the poly(ester amine)s (PEAs) were successfully prepared from low-molecular-weight PEI (Mn = 2000) and Poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCFC) copolymers using isophorone diisocyanate (IPDI) as cross-linker. The obtained PEAs copolymers are biodegradable and water-soluble. The PEAs/DNA complexes showed effective and stable DNA condensation with the particle size < or = 200 nm and zeta potential > or =10 mV, indicating its potential for intracellular delivery. Compared to the unmodified low-molecular-weight PEI, PEAs displayed similarly low cytotoxicity in all two cell lines (293T: Human kidney carcinoma, HUVEC: Human umbilical vein Endothelial cell) and revealed much higher transfection efficiency in 293T cell lines. Therefore these PEAs might be a novel safe and efficient polymeric gene delivery vectors.

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.

Synthesis of a novel biodegradable poly(ester amine) (PEAs) copolymer based on low-molecular-weight polyethyleneimine for gene delivery.

In this paper, a novel biodegradable poly(ester amine) (PEA) copolymer was successfully prepared from low-molecular-weight polyethyleneimine (PEI, Mn=1800) and poly(epsilon-caprolactone)-Pluronic-poly(epsilon-caprolactone) (PCFC) copolymers. According to the results of agarose gel electrophoresis, particle sizes and zeta potential measurement and transfection efficiency, these PEA copolymers showed great ability to condense plasmid DNA effectively into nano-complexes with small particle size (< or =200 nm) and moderate zeta potential (> or =12 mV) at proper polymeric carrier/DNA weight ratio. Compared with low-molecular-PEI (Mn=1800), the obtained PEAs exhibited higher transfection efficiency as well as lower cytotoxicity. These results indicated that such PEAs might have great potential application in gene delivery system.