We prepared polypseudorotaxanes (PPRXs) composed of cyclodextrin (CyD) and polyethylene glycol (PEG) inside microspheres (MSs) by an emulsifying process using polypropylene glycol (PPG) that shows temperature-dependent hydrophilicity changes; PPG is hydrophobic at high temperatures but hydrophilic at low temperatures. An aqueous solution of CyD and PEG was dispersed as droplets in PPG at 60°C then cooled to 0°C to allow water of droplets to transfer into PPG. On removal of water in the droplets, CyD and PEG were left behind as a CyD/PEG PPRX inside the solid-state MSs. Examination of α-, β-, and γ-CyD revealed that α-CyD was suitable for the formation of PPRX containing PEG in this MS preparation procedure. Interestingly, a new PPRX composed of α-CyD and PPG was formed in the α-CyD MSs when they were prepared in the absence of PEG from the aqueous solution of α-CyD. This MS fabrication procedure can control the size and shape of PPRX particles, and will contribute to the production of new types of CyD inclusion complexes. Key words cyclodextrin (CyD); microsphere (MS); polyethylene glycol (PEG); polypropylene glycol (PPG); polypseudorotaxane (PPRX)Cyclodextrins (CyDs) are cyclic oligosaccharides composed of 6, 7, or 8 glucopyranoside units, which are named α-, β-, and γ-CyD, respectively. CyDs consist of a hydrophobic cavity in which hydrophobic molecules are enclosed to form an inclusion complex. CyDs are widely used as a pharmaceutical additive for their ability to improve the solubility and stability of drugs via CyD complexation.
Microspheres (MS) are useful as drug carriers to improve the performance of therapeutic systems. For example, stable release by a valve and guaranteed delivery to the lung by a metered dose inhaler or dry powder inhaler formulations can be achieved using size-controlled spherical MS, 1) and the therapeutic drugs entrapped in MS and, when injected vascularly, can distribute to specific organs or tissues depending on their size. 2,3) The choice of the matrix material and size control of the MS are the most important factors in designing any therapeutic system. Lipophilic polymer esters such as poly(lactic-co-glycolic acid) are popular materials and exhibit prolonged drug release. On the other hand, hydrophilic polymers can be used for controlled release over shorter periods and may be better at entrapping MS for water-soluble drugs compared with lipophilic polymers. 4)MS consisting of hydrophilic polymers, such as proteins and polysaccharides, can be prepared by emulsion-evaporation and spray-drying. [5][6][7] Water is a good solvent for such polymers during the preparation processes. In most cases, cross-linking agents are used to ensure particle generation. 8)However, heating to evaporate water and addition of crosslinking agents may not be good for the stability of therapeutic drugs in MS.9,10) Although gelatin MS can be prepared in cooling processes to promote gel formation, cross-linking agents such as glutaraldehyde are needed to control drug release from the resulting MS.11) A novel preparation method for MS consisting of water soluble polymers, which can be applied to various types of polymers and does not require heating and cross-linking reactions during the preparation process, will be useful for the preparation of MS containing sensitive materials, such as protein drugs.In the present study, polypropyleneglycol (PPG) was used as a dispersion medium for the preparation of MS consisting of water-soluble polymers. PPG is hydrophobic at high temperatures but hydrophilic and freely soluble in water at low temperatures. Therefore, the PPG-water system forms two liquid phases like an emulsion at a high temperature and the system changes to a liquid phase on cooling. This temperature-dependent property of PPG can be used to remove water from aqueous polymer solutions dispersed in PPG to form solid polymer particles. Soluble starch is used mainly as the model water-soluble polymer. Gelatin, whey protein and dextran have also been used for MS preparation. ExperimentalMaterials Polypropyleneglycol (diol type 700, PPG) and soluble starch were purchased from Wako Pure Chemical (Osaka). Whey protein isolate (WPI) was kindly supplied by Snow Brand Milk Products (Tokyo). Dextran T70 and gelatin were purchased from Pharmacia Biotech (Uppsala, Sweden) and Nitta Gelatin (Osaka), respectively. All other chemicals were of reagent grade and used as received.Procedure for Microsphere Preparation Water soluble polymers (starch, gelatin, WPI or dextran T70) were initially dissolved in water (5-10%) at 60°C for the aqueous phas...
In the administration of vancomycin (VCM) for emergency and critically ill patients, insuf cient VCM trough concentrations were occasionally observed. We performed this study to identify independent risk factors related to VCM low trough concentrations (< 10 µg/mL) for emergency and critically ill patients. Forty-six patients treated with VCM based on therapeutic drug monitoring guidelines between January 2013 and December 2015 were enrolled. Risk factors associated with VCM low trough concentrations were examined by comparing various factors of patients. Multiple regression analysis showed that the initial trough concentrations of VCM were related to age, body weight, estimated glomerular ltration ratio (eGFR (mL/min/1.73m 2 )), presence of trauma, average urine volume, and daily dose of VCM. Additionally logistic regression analysis identi ed eGFR (adjusted odds ratio = 1.044, 95 con dence interval = 1.005 -1.085, P = 0.028), average urine volume (adjusted odds ratio = 1.066, 95 con dence interval = 1.018 -1.116, P = 0.007), and daily dose of VCM (adjusted odds ratio = 0.873, 95 con dence interval = 0.764 -0.998, P = 0.046) as being an independent risk factor associated with VCM low trough concentrations. Therefore, determining the daily dose of VCM in consideration of the eGFR and the average urine volume may prevent VCM low trough concentrations. Also, it is important to actively monitor since two factors change over time.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.