Tuning Size and Morphology of mPEG--p(HPMA-Bz) Copolymer Self-Assemblies Using Microfluidics.

The careful design of nanoparticles, in terms of size and morphology, is of great importance to developing effective drug delivery systems. The ability to precisely tailor nanoparticles in size and morphology during polymer self-assembly was therefore investigated. Four poly(ethylene glycol)--poly(-2-benzoyloxypropyl methacrylamide) mPEG--p(HPMA-Bz) block copolymers with a fixed hydrophilic block of mPEG 5 kDa and a varying molecular weight of the hydrophobic p(HPMA-Bz) block (A: 17.

Scale-Up of the Manufacturing Process To Produce Docetaxel-Loaded mPEG--p(HPMA-Bz) Block Copolymer Micelles for Pharmaceutical Applications.

An efficient, scalable, and good manufacturing practice (GMP) compatible process was developed for the production of docetaxel-loaded poly(ethylene glycol)--poly(-2-benzoyloxypropyl methacrylamide) (mPEG--p(HPMA-Bz)) micelles. First, the synthesis of the mPEG-p(HPMA-Bz) block copolymer was optimized through step-by-step investigation of the batch synthesis procedures. This resulted in the production of 1 kg of mPEG-p(HPMA-Bz) block copolymer with a 5 kDa PEG block and an overall molecular weight of 22.

Effect of Formulation and Processing Parameters on the Size of mPEG- b-p(HPMA-Bz) Polymeric Micelles.

Micelles composed of block copolymers of poly(ethylene glycol)- b-poly( N-2-benzoyloxypropyl methacrylamide) (mPEG- b-p(HPMA-Bz)) have shown great promise as drug-delivery carriers due to their excellent stability and high loading capacity. In the present study, parameters influencing micelle size were investigated to tailor sizes in the range of 25-100 nm. Micelles were prepared by a nanoprecipitation method, and their size was modulated by the block copolymer properties such as molecular weight, their hydrophilic-to-hydrophobic ratio, homopolymer content, as well as formulation and processing parameters.

Nanobody-functionalized polymersomes for tumor-vessel targeting.

Targeted carrier systems (e.g., liposomes or nanoparticles) are used to specifically deliver drugs to a site of interest.

Polymersome stomatocytes: controlled shape transformation in polymer vesicles.

We report here a controllable shape transformation of polymer vesicles (polymersomes) constructed from block copolymers of which the hydrophobic part is a high-molecular-weight glassy segment. Control over the shape transformation is obtained by kinetic manipulation of the phase behavior of this glassy hydrophobic segment. Kinetic manipulation of the phase behavior of polymer membranes allows for different shapes of polymersomes to be captured at specific times, which directly translates into physically robust nanostructures that are otherwise unobtainable.

Smart nanocontainers and nanoreactors.

We highlight recent advances in the synthesis of nanocarriers and nanoreactors from synthetic and biological building blocks with emphasis on the stimulus-responsive regulation of their function.

In-depth evaluation of the cycloaddition--retro-Diels--Alder reaction for in vivo targeting with [(111)In]-DTPA-RGD conjugates.

Introduction: The spontaneous copper-free tandem 1,3-dipolar cycloaddition-retro-Diels-Alder (tandem crDA) reaction between cyclic Arg-Gly-Asp-d-Phe-Orn(N(3)) [c(RGDfX)] and oxanorbornadiene-DTPA (o-DTPA) or methyloxanorbornadiene-DTPA (mo-DTPA) into two DTPA-c(RGDfX) regioisomers is characterized. Since there is no information on the stability and reaction rate of the tandem crDA reaction in biological media, we set out to characterize these reaction parameters.

Methods: The effects of concentration of the reactants, temperature, pH and reaction environment (serum, blood) on the kinetics of the reaction were determined using (111)In-labeled oxanorbornadiene-DTPA analogs.

"Clickable" elastins: elastin-like polypeptides functionalized with azide or alkyne groups.

Elastin-like polypeptides (ELPs) functionalized with azide or alkyne groups were produced biosynthetically and coupled via the Cu-catalyzed azide-alkyne cycloaddition to a variety of (bio)molecules.

Application of metal-free triazole formation in the synthesis of cyclic RGD-DTPA conjugates.

The tandem 1,3-dipolar cycloaddition-retro-Diels-Alder (tandem crDA) reaction is presented as a versatile method for metal-free chemoselective conjugation of a DTPA radiolabel to N-delta-azido-cyclo(-Arg-Gly-Asp-d-Phe-Orn-) via oxanorbornadiene derivatives. To this end, the behavior of several trifluoromethyl-substituted oxanorbornadiene derivatives in the 1,3-dipolar cycloaddition was studied and optimized to give a clean and efficient method for bio-orthogonal ligation in an aqueous environment. After radioisotope treatment, the resulting 111In-labeled c(RGD)-CF3-triazole-DTPA conjugate was subjected to preliminary biological evaluation and showed high affinity for alpha(v)beta(3) (IC(50)=192 nM) and favorable pharmacokinetics.