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Macromolecular prodrugs (MPDs) of aspirin and salicylic acid were synthesized by covalent attachment to hydroxypropylcellulose (HPC) using p-toluenesulfonyl chloride in N, N-dimethylacetamide. The present synthesis strategy resulted in organo-soluble MPDs with 78-86 % yield and degree of drug substitution 0.53-1.96 and 0.68-2.10 for aspirin and salicylic acid, respectively. The size exclusion chromatography showed DP 192 and 214 for HPC-aspirin and HPC-salicylic acid conjugates, respectively. HPC-aspirin and HPC-salicylic acid conjugates were found thermally more stable than native drugs. The activation energy ( Ea) of thermal degradation of drugs, polymer and prodrugs was calculated with the help of Broido and Chang kinetic models. Order of reaction ( n) was calculated from thermal data using Chang model. Various thermodynamic parameters, i.e., enthalpy (Δ H), Gibbs free energy (Δ G) and entropy (Δ S) were also calculated. Doyle's method was employed on thermal data of MPDs to calculate integral procedural decomposition temperature and comprehensive index of intrinsic thermal stability. Amphiphilic HPC-aspirin conjugates showed formation of nanoparticles at water/DMSO interface with size distribution from ~500 to 750 nm by transmission electron microscopy. [ABSTRACT FROM AUTHOR]

This article presents synthesis of novel macromolecular prodrugs of aceclofenac (an anti-inflammatory drug) onto hydroxypropylcellulose (HPC). The HPC-aceclofenac conjugates were prepared using an acylating agent 1,1′-carbonyldiimidazole (CDI) under homogenous reaction conditions. Aceclofenac was first activated by using CDI to form its N-acylimidazole. The N-acylimidazole of aceclofenac was then reacted with HPC polymer at 80 °C for 24 h. Highly pure prodrugs of aceclofenac were synthesized with a wide range of moderate to high degree of substitution (DS 0.41-2.12) as calculated by H NMR spectroscopy. The UV spectroscopic analysis has also revealed that the active drug aceclofenac was found in different conjugates from 28 to 67 mg/100 mg of HPC-aceclofenac conjugates which are in good agreement with DS calculated by H NMR spectroscopy. The gel permeation chromatography showed unimodal absorption that indicates no significant degradation in polymer chains during the reaction. The macromolecular prodrugs of aceclofenac were characterized using different spectroscopic and chromatographic techniques. The thermal analysis has revealed that HPC-aceclofenac conjugates (prodrugs) are 92 and 96 °C more stable than pure aceclofenac regarding their initial (Tdi) and maximum degradation temperatures (Tdm), respectively. The activation energy ( Ea) and frequency factor ( Z) of the degradation reactions were evaluated using Friedman, Broido and Chang methods. Degradation followed first order ( n) kinetics. Transmission electron microscopy has revealed the formation of sponge like nano aggregates with population size distribution of around 80-150 nm. [ABSTRACT FROM AUTHOR]

This article presents the synthesis of novel hydroxypropylmethylcellulose (HPMC)-aspirin (ASP) conjugates, i.e. macromolecular prodrugs, through the reaction of HPMC with ASP after its in situ activation by 4-methylbenzenesulfonyl chloride. The highly pure ASP prodrugs obtained by this homogeneous and elegant esterification method were characterized using different spectroscopic and chromatographic techniques. Nanoparticulate drug design was successfully achieved by the conversion of free hydroxyls of the polymer into acetates. Transmission electron microscopy and scanning electron microscopy showed nanoparticle formation with the major population size distribution of around 450 nm. Nevertheless, the pharmacokinetics of the HPMC conjugates were studied using high performance liquid chromatography. The pharmacokinetic data indicated that a single dose of 132.6 mg of HPMC-ASP was well tolerated in animal studies without any adverse effects. The maximum plasma concentration ( C) of HPMC-ASP was found to be 14.6 μg·L with a t of 1 h. The plasma half-life and clearance and the volume of HPMC-ASP distribution were 4.6 h, 3.23 L·h, and 21.8 L·kg, respectively. The elimination of HPMC-ASP followed first-order kinetics with r of 0.9643. The results presented in this paper show the great potential of HPMCASP as a more effective, safe, and stable prodrug. [InlineMediaObject not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Characterizing the mechanical properties of materials and biological systems at the nanoscale requires accurate measurement of forces on the order of μN and less. Due to the scale of the measurements and size of the instrumentation, calibration of nanoscale devices presents a new challenge in metrology. In order to ensure accuracy of results, traceable calibrations must be performed on nanoscale instrumentation. Our group recently developed a novel MEMS-based high resolution load cell with force resolution on the order of μN. This paper reports on a simple method for traceably calibrating our device using dead weights that could be generalized to other MEMS-based load cells. In this article, fabrication of a MEMS load cell is detailed and we compare our calibrated force–displacement curves to a non-linear theoretical prediction, revealing errors as great as 29%. [ABSTRACT FROM AUTHOR]