Solvent-Free Processing of Drug-Loaded Poly(ε-Caprolactone) Scaffolds with Tunable Macroporosity by Combination of Supercritical Foaming and Thermal Porogen Leaching

Demand of scaffolds for hard tissue repair increases due to a higher incidence of fractures related to accidents and bone-diseases that are linked to the ageing of the population. Namely, scaffolds loaded with bioactive agents can facilitate the bone repair by favoring the bone integration and avoiding post-grafting complications. Supercritical (sc-)foaming technology emerges as a unique solvent-free approach for the processing of drug-loadenu7d scaffolds at high incorporation yields. In this work, medicated poly(ε-caprolactone) (PCL) scaffolds were prepared by sc-foaming coupled with a leaching process to overcome problems of pore size tuning of the sc-foaming technique. The removal of the solid porogen (BA, ammonium bicarbonate) was carried out by a thermal leaching taking place at 37 °C and in the absence of solvents for the first time. Macroporous scaffolds with dual porosity (50–100 µm and 200–400 µm ranges) were obtained and with a porous structure directly dependent on the porogen content used. The processing of ketoprofen-loaded scaffolds using BA porogen resulted in drug loading yields close to 100% and influenced its release profile from the PCL matrix to a relevant clinical scenario. A novel solvent-free strategy has been set to integrate the incorporation of solid porogens in the sc-foaming of medicated scaffolds.

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Smoothened agonist sterosome immobilized hybrid scaffold for bone regeneration

Science Advances ◽

10.1126/sciadv.aaz7822 ◽

2020 ◽

Vol 6 (17) ◽

pp. eaaz7822 ◽

Cited By ~ 2

Author(s):

Chung-Sung Lee ◽

Soyon Kim ◽

Jiabing Fan ◽

Hee Sook Hwang ◽

Tara Aghaloo ◽

...

Keyword(s):

Bone Regeneration ◽

Cell Fate ◽

Bone Repair ◽

Drug Loading ◽

Three Dimensional ◽

Hedgehog Pathway ◽

Hybrid Scaffold ◽

Synergistic Activation ◽

Bioactive Agents ◽

Osteoinductive Property

Biomaterial delivery of bioactive agents and manipulation of stem cell fate are an attractive approach to promote tissue regeneration. Here, smoothened agonist sterosome is developed using small-molecule activators [20S-hydroxycholesterol (OHC) and purmorphamine (PUR)] of the smoothened protein in the hedgehog pathway as carrier and cargo. Sterosome presents inherent osteoinductive property even without drug loading. Sterosome is covalently immobilized onto three-dimensional scaffolds via a bioinspired polydopamine intermediate to fabricate a hybrid scaffold for bone regeneration. Sterosome-immobilized hybrid scaffold not only provides a favorable substrate for cell adhesion and proliferation but also delivers bioactive agents in a sustained and spatially targeted manner. Furthermore, this scaffold significantly improves osteogenic differentiation of bone marrow stem cells through OHC/PUR-mediated synergistic activation of the hedgehog pathway and also enhances bone repair in a mouse calvarial defect model. This system serves as a versatile biomaterial platform for many applications, including therapeutic delivery and endogenous regenerative medicine.

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Temperature Dependent Green Synthesis of 3-Carboxycoumarins and 3,4-unsubstituted Coumarins

Current Organic Synthesis ◽

10.2174/1570179415666180924124134 ◽

2019 ◽

Vol 16 (1) ◽

pp. 130-135 ◽

Cited By ~ 3

Author(s):

Jack van Schijndel ◽

Dennis Molendijk ◽

Luiz Alberto Canalle ◽

Erik Theodorus Rump ◽

Jan Meuldijk

Keyword(s):

Knoevenagel Condensation ◽

Ammonium Bicarbonate ◽

Solvent Free ◽

Temperature Dependent ◽

Step Procedure ◽

Synthetic Routes ◽

High Yields ◽

Temperature Optima ◽

Solvent Free Synthesis ◽

Full Conversion

Aim and Objective: Because of the low abundance of 3,4-unsubstituted coumarins in plants combined with the complex purification process required, synthetic routes towards 3,4-unsubstituted coumarins are especially valuable. In the present work, we explore the possibilities of a solvent-free Green Knoevenagel condensation on various 2-hydroxybenzaldehyde derivatives and malonic acid without the use of toxic organocatalysts like pyridine and piperidine but only use ammonium bicarbonate as the catalyst. Materials and Methods: To investigate the scope of the Green Knoevenagel condensation for the synthesis of 3,4-unsubstituted coumarins, various 2-hydroxybenzaldehyde derivatives were screened as starting material in the optimized two-step procedure developed for 2-hydroxybenzaldehyde. </P><P> Results: This study shows that the intramolecular esterification and the decarboxylation are in competition, but show different temperature optima. In order to suppress premature decarboxylation and maximize the yield of coumarin, a two-step procedure was adopted. The reaction mixture containing ammonium bicarbonate is initially kept at 90ºC for 1 hour. After completion of the cyclization, the temperature of the reaction mixture is increased to 140ºC for 2 hours. Following this protocol, coumarin could be isolated with a yield of 95%. Conclusion: A two-step procedure for the solvent-free synthesis of several 3,4-unsubstituted coumarins was developed using ammonium bicarbonate, resulting in high yields of the desired products. Moreover, this procedure has a low E-factor and is, therefore an environmental friendly reaction in line with the principles of Green Chemistry. It was shown that by initially capping the temperature at 90ºC, premature decarboxylation can be suppressed. After full conversion to the intermediate 3-carboxycoumarin, the temperature can be increased to 140ºC finalizing the reaction. Ammonium bicarbonate was shown to catalyze both the Green Knoevenagel condensation and the decarboxylation step.

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Sustainable Passerini-tetrazole three component reaction (PT-3CR): selective synthesis of oxaborol-tetrazoles

Chemical Communications ◽

10.1039/d1cc03256a ◽

2021 ◽

Vol 57 (76) ◽

pp. 9708-9711

Author(s):

Akansha Singh ◽

Ravindra Kumar

Keyword(s):

Solvent Free ◽

Selective Synthesis ◽

Three Component Reaction ◽

First Time

A sustainable catalyst- and solvent-free Passerini-tetrazole three component reaction (PT-3CR) has been developed for the selective synthesis of benzoxaborol-tetrazoles for the first time.

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Low-temperature and purification-free stereocontrolled ring-opening polymerisation of lactide in supercritical carbon dioxide

Green Chemistry ◽

10.1039/d0gc00352b ◽

2020 ◽

Vol 22 (7) ◽

pp. 2197-2202 ◽

Cited By ~ 3

Author(s):

Simon P. Bassett ◽

Andrew D. Russell ◽

Paul McKeown ◽

Isabel Robinson ◽

Thomas R. Forder ◽

...

Keyword(s):

Carbon Dioxide ◽

Low Temperature ◽

Supercritical Carbon Dioxide ◽

Ring Opening ◽

Solvent Free ◽

Free Ring ◽

First Time ◽

Supercritical Carbon

A stereoselective, solvent-free ring-opening polymerisation (ROP) of lactide (LA) in supercritical carbon dioxide (scCO2) is reported for the first time.

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Comparative Evaluation of Commercial Concentration Procedures for Human Intestinal Parasite Detection

Laboratory Medicine ◽

10.1093/labmed/lmy072 ◽

2018 ◽

Vol 50 (3) ◽

pp. 243-248 ◽

Cited By ~ 1

Author(s):

Denis Leméteil ◽

Gilles Gargala ◽

Romy Razakandrainibe ◽

Jean Jacques Ballet ◽

Loic Favennec ◽

...

Keyword(s):

Organic Solvent ◽

Comparative Evaluation ◽

Intestinal Parasite ◽

Solvent Free ◽

Parasite Detection ◽

Parasite Infections ◽

Stool Specimens ◽

Concentration Factors ◽

Commercial Kits ◽

First Time

AbstractBackgroundEffective stool concentration is essential in microscopically based diagnosis of human intestinal parasite infections.ObjectiveTo compare the performances of 4 concentration commercial kits and 1 homemade procedure in 96 clinical stool specimens that tested positive for the detection of 9 helminth and 8 protozoa parasites.MethodsThe presence or absence of parasite forms was microscopically determined under conditions of standard practice. Also, we established the accuracies, concentration factors, and extraction yields.ResultsNo difference was observed between procedures for preconcentration specimens that tested positive. However, for preconcentration specimens that tested negative, we discovered that the homemade procedure was the most effective, and 2 of the 4 commercial kits were discovered to be satisfactory for routine applications.ConclusionsFor all parasites, procedures with biphasic solvents exhibited higher performances than organic solvent-free procedures. For the first time, the effectiveness of commercial concentration kits has been evaluated on several common stool parasites, and the results suggest that improvement of commercial procedures is possible.

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A study of the Willgerodt–Kindler reaction to obtain thioamides and α-ketothioamides under solvent-less conditions

Canadian Journal of Chemistry ◽

10.1139/v2012-030 ◽

2012 ◽

Vol 90 (7) ◽

pp. 567-573 ◽

Cited By ~ 21

Author(s):

José Ernesto Valdez-Rojas ◽

Hulme Ríos-Guerra ◽

Alma Leticia Ramírez-Sánchez ◽

Guadalupe García-González ◽

Cecilio Álvarez-Toledano ◽

...

Keyword(s):

Solvent Free ◽

First Time ◽

Better Than

In this paper, the results obtained in the synthesis of thioamides and α-ketothioamides by a modification of the Willgerodt–Kindler reaction, under solvent-free and noncatalyst conditions using IR energy as a source of activation, are presented. The use of IR energy in these reactions has been shown to lead to a mixture of thioamide and α-ketothioamide as the main products in most cases, with the latter predominating. The yields of α-ketothioamides from most of these reactions are better than those reported previously. To the best of our knowledge, this is the first time that IR energy has been applied to promote the Willgerodt–Kindler reaction.

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Body temperature polymerization and in situ drug encapsulation in supercritical carbon dioxide

Polymer Chemistry ◽

10.1039/d0py01131b ◽

2020 ◽

Vol 11 (42) ◽

pp. 6821-6831

Author(s):

Zi-Kun Rao ◽

Tian-Qiang Wang ◽

Yang Li ◽

Hong-Yu Zhu ◽

Yu Liu ◽

...

Keyword(s):

Carbon Dioxide ◽

Body Temperature ◽

Supercritical Carbon Dioxide ◽

Solvent Free ◽

Drug Encapsulation ◽

First Time ◽

Supercritical Carbon

Body-temperature and solvent-free polymerization and in situ fabrication of drug-loaded microparticles are reported for the first time.

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Rapid mechanochemical synthesis of metal–organic frameworks using exogenous organic base

Dalton Transactions ◽

10.1039/d0dt01240h ◽

2020 ◽

Vol 49 (45) ◽

pp. 16238-16244 ◽

Cited By ~ 1

Author(s):

Zihao Wang ◽

Zongzhe Li ◽

Marcus Ng ◽

Phillip J. Milner

Keyword(s):

Mechanochemical Synthesis ◽

Metal Organic Frameworks ◽

Solvent Free ◽

Organic Base ◽

Metal Organic ◽

First Time ◽

Solvent Free Synthesis

We describe the mechanochemical, solvent-free synthesis of metal–organic frameworks using liquid organic base for the first time.

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Fluorescence-based techniques to assess the miscibility and physical stability of a drug–lipid complex

Canadian Journal of Chemistry ◽

10.1139/cjc-2018-0404 ◽

2019 ◽

Vol 97 (6) ◽

pp. 496-503 ◽

Cited By ~ 1

Author(s):

Jiahao Huang ◽

Peter X. Chen ◽

Shawn Wettig

Keyword(s):

Infrared Spectroscopy ◽

Fluorescence Microscopy ◽

Drug Loading ◽

Physical Stability ◽

Solvent Free ◽

Lipid Complex ◽

Pharmaceutical Dosage Form ◽

Free Condition ◽

Solvent Free Condition ◽

Model Complex

The objective of this study was to evaluate the feasibility of using fluorescence-based techniques to assess the miscibility and physical stability of a drug–lipid complex pharmaceutical dosage form under a solvent-free condition. An indomethacin–phospholipid complex (IDM–DPC) was used as model complex for this study. The miscibility of indomethacin within the phospholipid was assessed by fluorescence spectroscopy, fluorescence microscopy, and infrared spectroscopy. The miscibility limit of the complex system was determined by fluorescence to be 20%–30% drug loading content, showing good correlation with infrared spectroscopy. The physical stability of the IDM–DPC stored at 40 °C was evaluated by fluorescence microscopy. Indomethacin formulated in the lipid complex with an indomethacin loading not more than 30% remained in an amorphous state within a period of 21 days, whereas the samples with a drug loading over 30% started to crystallize earlier with increasing drug content. IDM–DPC having higher miscibilities were found to be more resistant to recrystallization under heating, thus having better physical stability. Fluorescence-based techniques showed convenience and promise in characterizing drug–lipid miscibility and predicting storage stability under a solvent-free condition.

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Self-assembly of pifithrin-α-loaded layered double hydroxide/chitosan nanohybrid composites as a drug delivery system for bone repair materials

Journal of Materials Chemistry B ◽

10.1039/c6tb02730j ◽

2017 ◽

Vol 5 (12) ◽

pp. 2245-2253 ◽

Cited By ~ 11

Author(s):

Yi-Xuan Chen ◽

Rong Zhu ◽

Zheng-liang Xu ◽

Qin-Fei Ke ◽

Chang-Qing Zhang ◽

...

Keyword(s):

Drug Delivery ◽

Drug Delivery System ◽

Layered Double Hydroxide ◽

Delivery System ◽

Self Assembly ◽

Bone Repair ◽

Repair Materials ◽

Double Hydroxide ◽

First Time ◽

Bone Repair Materials

The self-assembly of pifithrin-α-loaded layered double hydroxide/chitosan nanohybrid composites as a drug delivery system was demonstrated for the first time to improve the cytocompatibility and enhance the osteoinductivity for the treatment of bone defects.

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