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1.
J Zhejiang Univ Sci B ; 21(5): 394-399, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32425005

RESUMO

At the end of 2019, a new form of pneumonia disease known as the corona virus disease 2019 (COVID-19) rapidly spread throughout most provinces of China, and the total global number of COVID-19 cases has surpassed 500 000 by Mar. 27, 2020 (WHO, 2020). On Jan. 30, 2020, the World Health Organization (WHO) declared COVID-19 a global health emergency (WHO, 2020). COVID-19 causes most damage to the respiratory system, leading to pneumonia or breathing difficulties. The confirmed case fatality risk (cCFR) was estimated to be 5% to 8% (Jung et al., 2020). Besides physical pain, COVID-19 also induces psychological distress, with depression, anxiety, and stress affecting the general population, quarantined population, medical staff, and patients at different levels (Kang et al., 2020; Xiang et al., 2020). Previous research on patients in isolation wards highlighted the risk of depressed mood, fear, loneliness, frustration, excessive worries, and insomnia (Abad et al., 2010).


Assuntos
Infecções por Coronavirus/psicologia , Infecções por Coronavirus/terapia , Terapia do Comportamento Dialético , Pneumonia Viral/psicologia , Pneumonia Viral/terapia , Adulto , Ansiedade/terapia , Betacoronavirus , China , Depressão/terapia , Feminino , Humanos , Pandemias , Período Pós-Parto , Gravidez , Gestantes/psicologia
2.
J Zhejiang Univ Sci B ; 21(5): 416-422, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32425010

RESUMO

Severe cases infected with the coronavirus disease 2019 (COVID-19), named by the World Health Organization (WHO) on Feb. 11, 2020, tend to present a hypercatabolic state because of severe systemic consumption, and are susceptible to stress ulcers and even life-threatening gastrointestinal bleeding. Endoscopic diagnosis and treatment constitute an irreplaceable part in the handling of severe COVID-19 cases. Endoscopes, as reusable precision instruments with complicated structures, require more techniques than other medical devices in cleaning, disinfection, sterilization, and other reprocessing procedures. From 2016 to 2019, health care-acquired infection caused by improper endoscope reprocessing has always been among the top 5 on the list of top 10 health technology hazards issued by the Emergency Care Research Institute. Considering the highly infective nature of COVID-19 and the potential aerosol contamination therefrom, it is of pivotal significance to ensure that endoscopes are strictly reprocessed between uses. In accordance with the national standard "Regulation for Cleaning and Disinfection Technique of Flexible Endoscope (WS507-2016)," we improved the workflow of endoscope reprocessing including the selection of chemicals in an effort to ensure quality control throughout the clinical management towards COVID-19 patients. Based on the experience we attained from the 12 severe COVID-19 cases in our hospital who underwent endoscopy 23 times in total, the article provides an improved version of endoscopic reprocessing guidelines for bedside endoscopic diagnosis and treatment on COVID-19 patients for reference.


Assuntos
Infecções por Coronavirus/diagnóstico , Desinfecção/métodos , Endoscópios/virologia , Contaminação de Equipamentos/prevenção & controle , Pneumonia Viral/diagnóstico , Fluxo de Trabalho , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , China , Infecções por Coronavirus/terapia , Infecção Hospitalar/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Ácido Peracético , Equipamento de Proteção Individual , Pneumonia Viral/terapia , Esterilização/métodos
3.
Patient Prefer Adherence ; 9: 923-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26170642

RESUMO

BACKGROUND: Intravenous (IV), intramuscular (IM), and subcutaneous (SC) are the three most frequently used injection routes in medication administration. Comparative studies of SC versus IV, IM versus IV, or IM versus SC have been sporadically conducted, and some new findings are completely different from the dosage recommendation as described in prescribing information. However, clinicians may still be ignorant of such new evidence-based findings when choosing treatment methods. METHODS: A literature search was performed using PubMed, MEDLINE, and Web of Sciences™ Core Collection to analyze the advantages and disadvantages of SC, IV, and IM administration in head-to-head comparative studies. RESULTS: "SC better than IV" involves trastuzumab, rituximab, antitumor necrosis factor medications, bortezomib, amifostine, recombinant human granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor, recombinant interleukin-2, immunoglobulin, epoetin alfa, heparin, and opioids. "IV better than SC" involves ketamine, vitamin K1, and abatacept. With respect to insulin and ketamine, whether IV has advantages over SC is determined by specific clinical circumstances. "IM better than IV" involves epinephrine, hepatitis B immu-noglobulin, pegaspargase, and some antibiotics. "IV better than IM" involves ketamine, morphine, and antivenom. "IM better than SC" involves epinephrine. "SC better than IM" involves interferon-beta-1a, methotrexate, human chorionic gonadotropin, hepatitis B immunoglobulin, hydrocortisone, and morphine. Safety, efficacy, patient preference, and pharmacoeconomics are four principles governing the choice of injection route. Safety and efficacy must be the preferred principles to be considered (eg, epinephrine should be given intramuscularly during an episode of systemic anaphylaxis). If the safety and efficacy of two injection routes are equivalent, clinicians should consider more about patient preference and pharmacoeconomics because patient preference will ensure optimal treatment adherence and ultimately improve patient experience or satisfaction, while pharmacoeconomic concern will help alleviate nurse shortages and reduce overall health care costs. Besides the principles, the following detailed factors might affect the decision: patient characteristics-related factors (body mass index, age, sex, medical status [eg, renal impairment, comorbidities], personal attitudes toward safety and convenience, past experience, perception of current disease status, health literacy, and socioeconomic status), medication administration-related factors (anatomical site of injection, dose, frequency, formulation characteristics, administration time, indication, flexibility in the route of administration), and health care staff/institution-related factors (knowledge, human resources). CONCLUSION: This updated review of findings of comparative studies of different injection routes will enrich the knowledge of safe, efficacious, economic, and patient preference-oriented medication administration as well as catching research opportunities in clinical nursing practice.

4.
Ther Clin Risk Manag ; 11: 393-406, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25767393

RESUMO

BACKGROUND: Medication errors may occur during prescribing, transcribing, prescription auditing, preparing, dispensing, administration, and monitoring. Medication administration errors (MAEs) are those that actually reach patients and remain a threat to patient safety. The Joint Commission International (JCI) advocates medication error prevention, but experience in reducing MAEs during the period of before and after JCI accreditation has not been reported. METHODS: An intervention study, aimed at reducing MAEs in hospitalized patients, was performed in the Second Affiliated Hospital of Zhejiang University, Hangzhou, People's Republic of China, during the journey to JCI accreditation and in the post-JCI accreditation era (first half-year of 2011 to first half-year of 2014). Comprehensive interventions included organizational, information technology, educational, and process optimization-based measures. Data mining was performed on MAEs derived from a compulsory electronic reporting system. RESULTS: The number of MAEs continuously decreased from 143 (first half-year of 2012) to 64 (first half-year of 2014), with a decrease in occurrence rate by 60.9% (0.338% versus 0.132%, P<0.05). The number of MAEs related to high-alert medications decreased from 32 (the second half-year of 2011) to 16 (the first half-year of 2014), with a decrease in occurrence rate by 57.9% (0.0787% versus 0.0331%, P<0.05). Omission was the top type of MAE during the first half-year of 2011 to the first half-year of 2014, with a decrease by 50% (40 cases versus 20 cases). Intravenous administration error was the top type of error regarding administration route, but it continuously decreased from 64 (first half-year of 2012) to 27 (first half-year of 2014). More experienced registered nurses made fewer medication errors. The number of MAEs in surgical wards was twice that in medicinal wards. Compared with non-intensive care units, the intensive care units exhibited higher occurrence rates of MAEs (1.81% versus 0.24%, P<0.001). CONCLUSION: A 3-and-a-half-year intervention program on MAEs was confirmed to be effective. MAEs made by nursing staff can be reduced, but cannot be eliminated. The depth, breadth, and efficiency of multidiscipline collaboration among physicians, pharmacists, nurses, information engineers, and hospital administrators are pivotal to safety in medication administration. JCI accreditation may help health systems enhance the awareness and ability to prevent MAEs and achieve successful quality improvements.

5.
Macromol Biosci ; 14(4): 526-36, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24273081

RESUMO

This paper reports a drug nanovehicle self-assembled from an amine-functionalized block copolymer poly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione)-block-poly(1,3-dioxepan-2-one) (PADMC-b-PTeMC), which is prepared by controlable ring-opening block copolymerization attractively in a "one-shot feeding" pathway. The copolymers display high cell-biocompatibility with no apparent cytotoxicities detected in 293T and HeLa cells. Due to their amphiphilic nature, PADMC-b-PTeMC copolymers can self-assemble into nanosized micelles capable of loading anticancer drugs such as camptothecin (CPT) and doxorubicin (DOX). In particular, the outer PADMC shell endows the PADMC-b-PTeMC nanomicelles with pH-dependent control over the micellar morphology, cell uptake efficiency, and the drug release pattern. Confocal inspection reveals the remarkably enhanced cellular internalization of drug loaded micelles by cancerous HeLa cells at relatively lower pH 5.8 simulating the mildly acid microenvironment in tumors. Along with the acidity-triggered volume expansion of micelles, an accelerated CPT release in vitro occurs. The obtained results adumbrate the possibility of completely biodegradable PADMC-b-PTeMC as pH-sensitive drug carriers for tumor chemotherapy.


Assuntos
Di-Hidropiridinas/administração & dosagem , Liberação Controlada de Fármacos , Neoplasias/tratamento farmacológico , Polímeros/administração & dosagem , Aminas/administração & dosagem , Aminas/química , Camptotecina/administração & dosagem , Camptotecina/química , Di-Hidropiridinas/química , Doxorrubicina/administração & dosagem , Doxorrubicina/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Polímeros/química
6.
Ther Clin Risk Manag ; 8: 393-401, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23185120

RESUMO

A utilization study was performed in a 2200-bed tertiary care teaching hospital. Data mining was performed on all nasogastric medication prescriptions for patients hospitalized in 2011. Nurses were interviewed by questionnaire. A PDCA (Plan-Do-Check-Act) cycle was used for continuous quality improvement. The proportion of patients with nasogastric tubes (NGT) was 3.2%. A large number of medical orders (n = 6261) involved nasogastric medications with a package insert particularly noting that they should not be crushed or opened (group 1) or medications without a specific formulation recommendation in the package insert but having evidence discouraging NGT dosing (group 2). Of the nasogastrically administered sustained-release or controlled-release formulations, a sustained-release sodium valproate tablet formulation was the most prescribed drug and a sustained-release 2.5 mg felodipine tablet was prescribed with the highest proportion of NGT dosing [NGT/(NGT + oral) = 12.3%]. Among the nasogastrically administered enteric-coated formulations, a myrtol-standardized enteric-coated capsule formulation was the most prescribed drug and a pantoprazole tablet formulation was prescribed with the highest proportion of NGT dosing [NGT/(NGT + oral) = 19.3%]. Proportions of NGT dosing for amiodarone and carbamazepine (group 2) were 4.8% and 6.3%, respectively. The percentage of nurses with adequate knowledge about pharmaceutical dosage formulations was 60%. The rate of answering correctly as to whether medications in group 1 could be crushed or opened was only 30%. Awareness of evidence discouraging NGT dosing of medications in group 2 was zero. Most nurses (90%) left physicians and pharmacists with the entire responsibility for knowledge and decision-making concerning route of drug administration. After a 3-month preliminary intervention, irrational medical orders involving nasogastric administration of medications in group 1 were successfully abolished. The rate of answering correctly as to whether medications in group 1 could be crushed or opened increased to 100%. This utilization study indicates poor awareness concerning nasogastric administration of medication on the part of physicians and nurses, and preliminary intervention measures were efficient in improving knowledge through team cooperation and effort.

7.
Macromol Biosci ; 12(12): 1689-96, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23076737

RESUMO

This paper reports a novel amphoteric aliphatic polycarbonate bearing both amine and carboxyl groups. In the absence of protection-deprotection chemistry, the multi-functionalized copolymer is synthesized by one-step enzymatic copolymerization. The influences of the reaction conditions including monomer feed ratio and polymerization time are explored. The simultaneous incorporation of amine and carboxyl functionalities provides the copolymer with a pH-tunable self-aggregation feature, leading to various aggregation states including precipitated agglomerate, well-dispersed positively or negatively charged nanoparticles in a controlled manner. The copolymer displays minimal cytotoxicity to 293T and HeLa cells.


Assuntos
Materiais Biocompatíveis , Vias Biossintéticas/fisiologia , Carbonatos/química , Polímeros/química , Aminas/química , Tampões (Química) , Dióxido de Carbono/química , Sistemas de Liberação de Medicamentos/métodos , Células HEK293 , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Estrutura Molecular
8.
Pharm Res ; 29(6): 1582-94, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22271048

RESUMO

PURPOSE: To design functional drug carriers for fast pH-responsive drug release. METHODS: Functional diblock terpolymers of monomethoxy poly(ethylene glycol)-block- copoly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione-co-ε-caprolactone) [mPEG-b-poly(ADMC-co-CL)] were fabricated via biosynthetic pathway. The self-assembled nanosphere and drug-loaded micelles of the copolymers were further prepared by dialysis method. The pH-tunable morphology variation and drug release pattern were observed at different pH. RESULTS: A collection of three PEGylated terpolymers with varied compositions in poly(ADMC-co-CL) block was designed with high cell-biocompatibility. The copolymers could readily self-assemble into nanoscale micelles (~ 100 nm) in aqueous medium and exhibit high stability over 80-h incubation in different mediums including deionized water, neutral NaCl solution, and heparin sodium solution. Due to the protonation-deprotonation of tertiary amine groups in ADMC units, acid-induced structural deformation of micelles was disclosed in terms of the variation in CAC value and hydrodynamic size at different pH. Drug loading efficiency was comparable to that of reported PEG-polyester micelles with specifically designed structures purposed for drug-loading improvement. Remarkably accelerated drug release triggered by acidity was distinctly detected for ibuprofen-loaded mPEG-b-poly(ADMC-co-CL) micelle system, suggesting a fast pH-responsive characteristic. CONCLUSION: Functional PEG-stabilized micellar carriers with positively charged polyester core were successfully developed for fast pH-responsive drug release.


Assuntos
Anti-Inflamatórios não Esteroides/química , Materiais Biocompatíveis , Portadores de Fármacos , Ibuprofeno/química , Poliésteres/química , Polietilenoglicóis/química , Animais , Células COS , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Chlorocebus aethiops , Diálise , Composição de Medicamentos , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Micelas , Nanosferas , Tamanho da Partícula , Poliésteres/síntese química , Poliésteres/toxicidade , Polietilenoglicóis/síntese química , Polietilenoglicóis/toxicidade , Solubilidade , Propriedades de Superfície , Tecnologia Farmacêutica/métodos
9.
Acta Biomater ; 8(2): 589-98, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21925625

RESUMO

The present paper reports the design and preparation of an amphiphilic triblock co-polymer poly(ε-caprolactone) (PCL)-poly(6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione) (PADMC)-PCL and the use of micelles composed of them as carriers for pH-sensitive drug release. The triblock co-polymers were synthesized via two-step ring-opening polymerization with catalysis by Novozym-435 lipase. By adjusting the feed ratio, three co-polymers with different PCL lengths and the same PADMC length were produced. The block structure of the co-polymers obtained was confirmed by comparative studies on PCL-PADMC-PCLs and the corresponding random poly(ε-caprolactone-random-6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione) (poly(CL-r-ADMC)) by means of nuclear magnetic resonance and differential scanning calorimetry. Cell cytotoxicity tests showed that the co-polymer displayed no apparent cytotoxicity to 293T and HeLa cells. Transmissions electron microscopy indicates that the self-assembled micelles exhibited a well-defined spherical shape with a diameter between ∼30 and 50 nm. The critical aggregation concentration was dependent on the block composition. Due to the presence of ionizable tertiary amine groups in the PADMC block, acid-induced variation in the micellar morphology was evident with respect to micelle size and size distribution. The size-pH curve was characterized by a smooth sigmoid form, and had a dramatic upward shift with decreasing pH from 6.5 to 4.5, which correlated well with the buffer range of hydrophilic PADMC. As a demonstration of the potential of PCL-PADMC-PCL micelles to control drug delivery, acid induced drug release for prednisone acetate-loaded micelles was explored. PCL-PADMC-PCL micelles show good promise as smart drug carriers, sensing the local specific pH decrease around lesion sites.


Assuntos
Aminas/química , Micelas , Cimento de Policarboxilato/química , Varredura Diferencial de Calorimetria , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Epotilonas/síntese química , Epotilonas/química , Epotilonas/farmacologia , Fluorescência , Células HEK293 , Células HeLa , Humanos , Hidrodinâmica , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Luz , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Transmissão , Cimento de Policarboxilato/síntese química , Cimento de Policarboxilato/farmacologia , Poliésteres/síntese química , Poliésteres/química , Poliésteres/farmacologia , Polimerização/efeitos dos fármacos , Prednisona/farmacologia , Espalhamento de Radiação , Temperatura , Água/química
10.
Biomaterials ; 32(36): 9925-39, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21930297

RESUMO

The aim of this contribution is to develop a universal method to promote the serum-tolerant capability of polycation-based gene delivery system. A "hydroxylation camouflage" strategy was put forward by coating the polycation vectors with hydroxyl-enriched "skin". Branched polyethyleneimine (PEI) was herein used as the polycation model and modified via the catalyst-free aminolysis reaction with 5-ethyl-5-(hydroxymethyl)-1,3-dioxan-2-oxo (EHDO). PEI-g-EHDO, PEI and alkylated PEI derivative termed as PEI-g-DPA were comparatively explored with respect to the transfection efficiency in the serum-free and serum-conditioned medium. The resultant data indicate that the serum-tolerant capability largely depended on the surface composition and substitution degree. In addition to the reduced surface charge, the introduced function caused by hydroxyl coating is believed to play a crucial role for the improved properties of PEI-g-EHDOs. The EHDO modification can effectively inhibit the adsorption of BSA proteins onto polyplexes surface. And the polyplexes stability was remarkably enhanced in the presence of DNase and heparin after EHDO modification. Note that the transfection activity of PEI-g-EHDO(34.5%) in the serum-conditioned medium was even higher than that without serum addition. In contrast, serum addition led to appreciable reduction in the transfection efficiency mediated by PEI and PEI-g-DPAs. Specifically, as far as the transfection activity in the presence of serum is concerned, PEI-g-EHDO could be up to 30-fold higher than unmodified PEI25k. PEI-g-EHDO(34.5%) displayed little to no hemolytic effect and high cell-biocompatibility with nearly no cytotoxicity detected in 293T cells and HeLa cells. Taking into account the high biocompatibility and serum-tolerant transfection activity, PEI-g-EHDO(34.5%) holds great potential for the use as efficient gene vector. More importantly, it is expected that such "hydroxylation camouflage" strategy may be universally applicable for a majority of existing polycation vectors.


Assuntos
Vetores Genéticos/metabolismo , Poliaminas/metabolismo , Soro/metabolismo , Transfecção/métodos , Adsorção/efeitos dos fármacos , Animais , Bovinos , Morte Celular/efeitos dos fármacos , Desoxirribonucleases/metabolismo , Eletroforese em Gel de Ágar , Ensaio de Desvio de Mobilidade Eletroforética , Células HEK293 , Células HeLa , Hemólise/efeitos dos fármacos , Heparina/farmacologia , Humanos , Hidroxilação/efeitos dos fármacos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Espectroscopia de Ressonância Magnética , Microscopia Confocal , Tamanho da Partícula , Polietilenoimina/síntese química , Polietilenoimina/química , Coelhos , Soroalbumina Bovina/metabolismo , Espectrofotometria Infravermelho , Propriedades de Superfície/efeitos dos fármacos
11.
Macromol Rapid Commun ; 32(4): 390-6, 2011 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-21433189

RESUMO

We herein develop a facile catalyst-free method to prepare hyperbranched hydroxyl-enriched aliphatic polycarbonate according to SCROP strategy. PEG-attached multiarm hyperbranched copolymer HEHDO-star-mPEG was further designed. It was found that HEHDO-star-mPEG can self-assemble into supramolecular multimolecular micelles in water. HEHDO-star-mPEG micelle showed excellent stability with respect to micellar size upon dilution, and displayed good cell-biocompatibility. An anticancer drug of doxorubicin with hydrogen-bonding functionality was incorporated into obtained micelles to establish a drug delivery system model. A high drug-loading content as well as sustained release pattern for HEHDO-star-mPEG based delivery system was achieved.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/instrumentação , Cimento de Policarboxilato/química , Polímeros/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Estabilidade de Medicamentos , Humanos , Micelas , Estrutura Molecular
12.
Biomacromolecules ; 11(10): 2550-7, 2010 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-20836520

RESUMO

Degradable polymers with specifically designed functionality have wide applications in biomedical fields. We reported herein the synthesis and characterization of a water-soluble and fast-degradable polycarbonate, functionalized with tertiary amine groups in the backbone. A novel cyclic carbonate monomer, namely, 6,14-dimethyl-1,3,9,11-tetraoxa-6,14-diaza-cyclohexadecane-2,10-dione (ADMC)(2), was synthesized and polymerized to provide the title polycarbonate [poly(ADMC)] via Novozym-435 lipase or tin(II) 2-ethylheaxanoate [Sn(Oct)(2)] catalyzed ring-opening polymerization (ROP). Novozym-435 lipase exhibited high activity toward the ROP in terms of molecular weight (M(n)) and monomer conversion, whereas the attempt with Sn(Oct)(2) failed. In the presence of molecular sieves-4 Å, the highest M(n) value of 1.2 × 10(4) g/mol was obtained in toluene with an initial monomer concentration of 0.58 M at 75 °C in the presence of 10 wt % of Novozym-435 to the monomer. Parameters that influence the polymerization, including reaction temperature, enzyme concentration, monomer concentration, and solvent composition, were investigated systematically. The resultant data suggested "living" characteristics for this enzyme-catalyzed polymerization, and the "living" feature seemed independent of the lipase concentration. The polymerization conducted in mixed solvents (toluene/isooctane) showed that product M(n)s were heavily dependent on the solvent composition. Poly(ADMC) was demonstrated to be amorphous by DSC technique. The obtained poly(ADMC) was found to be soluble in most of the organic solvents and interestingly in H(2)O as well. In vitro hydrolytic degradation of poly(ADMC) as monitored by GPC indicated the degradation was a relatively fast process. HPLC-ESI/MS and (1)H NMR analyses demonstrated that N-methyl diethanolamine was the main product after degradation. Poly(ADMC) presented low cytotoxicity toward human cervix carcinoma (HeLa) cells and hepatoblastoma cells (Hep G2), as demonstrated by MTT assay.


Assuntos
Aminas/química , Materiais Biocompatíveis/síntese química , Compostos Heterocíclicos com 1 Anel/síntese química , Lactonas/síntese química , Poliésteres/síntese química , Materiais Biocompatíveis/efeitos adversos , Materiais Biocompatíveis/química , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Compostos Heterocíclicos com 1 Anel/efeitos adversos , Compostos Heterocíclicos com 1 Anel/química , Humanos , Lactonas/efeitos adversos , Lactonas/química , Lipase/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Poliésteres/efeitos adversos , Poliésteres/química , Polimerização , Solubilidade , Espectrometria de Massas por Ionização por Electrospray , Água/química
13.
Acta Biomater ; 6(11): 4285-95, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20601231

RESUMO

Novel functional biodegradable gene vectors, poly(L-succinimide)-g-polyethylenimines-g-poly(ethylene glycol) (PSI-g-PEI-g-PEGs) were synthesized by conjugating methoxy poly(ethylene glycol) (mPEG, M(w)=750 Da) to PEI segments (M(w)=800 Da) of PSI-g-PEI. The physicochemical properties of PSI-g-PEI-g-PEGs, including buffering capability, pDNA binding ability, cytotoxicity, zeta potential and the particle size of polymer/pDNA complexes, were explored. The influence of PEGylation was discussed based on a comparative study of PSI-g-PEI-g-PEGs, PSI-g-PEI and PEI25k (M(w)=25 kDa). SEM images revealed that PSI-g-PEI-g-PEG/pDNA particles have a regular shape with the diameter ranging from 70 to 170 nm. PEGylation could suppress the aggregation occurrence between complexes, resulting in a reduction of the polymer/pDNA complex size. PSI-g-PEI-g-PEGs exhibited remarkably lower cytotoxicity compared to PSI-g-PEI and PEI25k. In 293T and HeLa cells, the obtained PSI-g-PEI-g-PEGs showed very high transfection efficiency compared to PEI25k. Fluorescent confocal microscopy demonstrated that PSI-g-PEI-g-PEGs could effectively transport pGL-3 plasmids into the nuclei of HeLa cells. Taking into account the continued high transfection efficacy and decreased toxicity after PEG modification, PSI-g-PEI-g-PEGs show great potential as the non-viral vectors for gene transfection.


Assuntos
Materiais Biocompatíveis/metabolismo , Vetores Genéticos/genética , Polietilenoglicóis/metabolismo , Polietilenoimina/metabolismo , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/química , Tampões (Química) , Morte Celular/efeitos dos fármacos , Eletroforese em Gel de Ágar , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Células HeLa , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Luciferases/metabolismo , Espectroscopia de Ressonância Magnética , Microscopia Confocal , Microscopia Eletrônica de Varredura , Peso Molecular , Tamanho da Partícula , Polietilenoglicóis/síntese química , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Polietilenoimina/síntese química , Polietilenoimina/química , Polietilenoimina/toxicidade , Titulometria , Transfecção , Vírus/genética
14.
ACS Appl Mater Interfaces ; 1(12): 2729-37, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20356150

RESUMO

AB type diblock methoxy poly(ethylene glycol)-b-poly(tetramethylene carbonate) (mPEG-PTeMC) copolymers were designed for the first time and used as carriers for the sustained release of the hydrophobic drug ibuprofen. In this paper, we developed a facile ring-opening polymerization (ROP) method to prepare mPEG-PTeMC copolymers under the catalysis of Novozym-435 lipase. Attractively, the polymerization has been successfully performed at 30 degrees C, close to room temperature. The data show that the copolymer compositions agree well with the feed ratio of TeMC to mPEG, indicating the controllable feature of the polymerization. The copolymer structures were characterized by (1)H NMR, IR, SEC, and DSC measurements. mPEG-PTeMC exhibits no apparent in vitro cytotoxicity toward human embryonic kidney transformed 293T cells. Those amphiphilic copolymers can readily self-assemble into nanosized micelles (about 150 nm) in aqueous solution. Their critical micelle concentrations are in the range of (1.6-9.3) x 10(-7) mol/L, determined by fluorescence spectroscopy. The micelles present high stability in PBS solution, with no obvious change in micelle diameters over 5 days. Ibuprofen can be loaded effectively in mPEG-PTeMC micelles, and its sustained release behavior is observed. Transmission electron microscopy shows that the well-dispersed spherical micelles are around 25 nm in diameter, while the diameter is 30 nm after loading ibuprofen. The release rate increases when the chain length of the PTeMC block decreases. These properties show that the micelles self-assembled from mPEG-PTeMC copolymers would have great potential as carriers for the effective encapsulation as well as sustained release of hydrophobic drugs.


Assuntos
Portadores de Fármacos/síntese química , Ibuprofeno/farmacologia , Micelas , Polietilenoglicóis/síntese química , Biocatálise/efeitos dos fármacos , Varredura Diferencial de Calorimetria , Morte Celular/efeitos dos fármacos , Linhagem Celular , Cromatografia em Gel , Portadores de Fármacos/química , Fluorescência , Humanos , Lipase/metabolismo , Espectroscopia de Ressonância Magnética , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Polietilenoglicóis/química , Polietilenoglicóis/toxicidade , Espectrofotometria Infravermelho , Temperatura , Fatores de Tempo
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