Dataset Information

Monitoring the erosion of hydrolytically-degradable nanogels via multiangle light scattering coupled to asymmetrical flow field-flow fractionation.

ABSTRACT: We describe the synthesis and characterization of degradable nanogels that display bulk erosion under physiologic conditions (pH = 7.4, 37 degrees C). Erodible poly(N-isopropylmethacrylamide) nanogels were synthesized by copolymerization with N,O-(dimethacryloyl) hydroxylamine, a cross-linker previously used in the preparation of nontoxic and biodegradable bulk hydrogels. To monitor particle degradation, we employed multiangle light scattering and differential refractometry detection following asymmetrical flow field-flow fractionation. This approach allowed the detection of changes in nanogel molar mass and topology as a function of both temperature and pH. Particle erosion was evident from both an increase in nanogel swelling and a decrease in scattering intensity as a function of time. Following these analyses, the samples were recovered for subsequent characterization by direct particle tracking, which yields hydrodynamic size measurements and enables number density determination. Additionally, we confirmed the conservation of nanogel stimuli-responsivity through turbidity measurements. Thus, we have demonstrated the synthesis of degradable nanogels that erode under conditions and on time scales that are relevant for many drug delivery applications. The combined separation and light scattering detection method is demonstrated to be a versatile means to monitor erosion and should also find applicability in the characterization of other degradable particle constructs.

SUBMITTER: Smith MH

PROVIDER: S-EPMC2810709 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Monitoring the erosion of hydrolytically-degradable nanogels via multiangle light scattering coupled to asymmetrical flow field-flow fractionation.

Smith Michael H MH South Antoinette B AB Gaulding Jeffrey C JC Lyon L Andrew LA

Analytical chemistry 20100101 2

We describe the synthesis and characterization of degradable nanogels that display bulk erosion under physiologic conditions (pH = 7.4, 37 degrees C). Erodible poly(N-isopropylmethacrylamide) nanogels were synthesized by copolymerization with N,O-(dimethacryloyl) hydroxylamine, a cross-linker previously used in the preparation of nontoxic and biodegradable bulk hydrogels. To monitor particle degradation, we employed multiangle light scattering and differential refractometry detection following a ...[more]

PMID: 20000662

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Project description:Liposomal formulations for the treatment of cancer and other diseases are the most common form of nanotechnology enabled pharmaceuticals (NEPs) submitted for market approval and in clinical application today. The accurate characterization of their physical-chemical properties is a key requirement; in particular, size, size distribution, shape, and physical-chemical stability are key among properties that regulators identify as critical quality attributes. Here we develop and validate an optimized method, based on multi-detector asymmetrical-flow field flow fractionation (MD-AF4) to accurately and reproducibly separate liposomal drug formulations into their component populations and to characterize their associated size and size distribution, whether monomodal or polymodal in nature. In addition, the results show that the method is suitable to measure liposomes in the presence of serum proteins and can yield information on the shape and physical stability of the structures. The optimized MD-AF4 based method has been validated across different instrument platforms, three laboratories, and multiple drug formulations following a comprehensive analysis of factors that influence the fractionation process and subsequent physical characterization. Interlaboratory reproducibility and intra-laboratory precision were evaluated, identifying sources of bias and establishing criteria for the acceptance of results. This method meets a documented high priority need in regulatory science as applied to NEPs such as Doxil and can be adapted to the measurement of other NEP forms (such as lipid nanoparticle therapeutics) with some modifications. Overall, this method will help speed up development of NEPS, and facilitate their regulatory review, ultimately leading to faster translation of innovative concepts from the bench to the clinic. Additionally, the approach used in this work (based on international collaboration between leading non-regulatory institutions) can be replicated to address other identified gaps in the analytical characterization of various classes of NEPs. Finally, a plan exists to pursue more extended interlaboratory validation studies to advance this method to a consensus international standard.

Dataset Information

Monitoring the erosion of hydrolytically-degradable nanogels via multiangle light scattering coupled to asymmetrical flow field-flow fractionation.

Publications

Monitoring the erosion of hydrolytically-degradable nanogels via multiangle light scattering coupled to asymmetrical flow field-flow fractionation.

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