Microfluidic Assembly To Synthesize Dual Enzyme/Oxidation-Responsive Polyester-Based Nanoparticulates with Controlled Sizes for Drug Delivery.

Controlling the size and narrow size distribution of polymer-based nanocarriers for targeted drug delivery is an important parameter that significantly influences their colloidal stability, biodistribution, and targeting ability. Herein, we report a high-throughput microfluidic process to fabricate colloidally stable aqueous nanoparticulate colloids with tunable sizes at 50-150 nm and narrow size distribution. The nanoparticulates are designed with different molecular weight polyesters having both ester bonds (responsive to esterase) and sulfide linkages (to oxidative reaction) on the backbones, thus exhibiting dual esterase/oxidation responses, causing the destabilization of the nanoparticulates to lead to the controlled release of encapsulated therapeutics.

Traceable PEO-poly(ester) micelles for breast cancer targeting: The effect of core structure and targeting peptide on micellar tumor accumulation.

Traceable poly(ethylene oxide)-poly(ester) micelles were developed through chemical conjugation of a near-infrared (NIR) dye to the poly(ester) end by click chemistry. This strategy was tried for micelles with poly(ε-caprolactone) (PCL) or poly(α-benzyl carboxylate-ε-caprolactone) (PBCL) cores. The surface of both micelles was also modified with the breast cancer targeting peptide, P18-4.

Micellar nano-carriers for the delivery of STAT3 dimerization inhibitors to melanoma.

The objective of this research was to develop polymeric micellar formulations of inhibitors of signal transducer and activator of transcription 3 (STAT3) dimerization, i.e., S3I-1757 and S3I-201, and evaluate the activity of successful formulations in B16-F10 melanoma, a STAT3 hyperactive cancer model, in vitro and in vivo.

Self-Associating Poly(ethylene oxide)-block-poly(α-carboxyl-ε-caprolactone) Drug Conjugates for the Delivery of STAT3 Inhibitor JSI-124: Potential Application in Cancer Immunotherapy.

Constitutive activation of signal transducer and activator of transcription 3 (STAT3) in tumor cells and tumor associated dendritic cells (DCs) plays a major role in the progression of cancer. JSI-124 (cucurbitacin I) is a potent inhibitor of STAT3; however, its poor solubility and nonspecificity limit its effectiveness in cancer immunotherapy. In order to achieve a nanocarrier for solubilization and passive targeting of JSI-124 to tumor cells and tumor associated DCs, the drug was chemically conjugated to pendent COOH groups of self-associating poly(ethylene oxide)-block-poly(α-carboxylate-ε-caprolactone) (PEO-b-PCCL).

Polymeric micelles for MCL-1 gene silencing in breast tumors following systemic administration.

Aim: To develop delivery systems for efficient siRNA delivery to breast cancer.

Methods: Poly(ethylene oxide)-block-poly(ϵ-caprolactone-grafted-spermine) (PEO-b-P(CL-g-SP)) micelles were modified with cholesterol group in their core and with RGD4C peptide on their shell. Transfection efficiency of complexed MCL-1 siRNA in MDA-MB-435 was investigated, in vitro and in vivo following intratumoral and intravenous injection.

Microfluidics: a transformational tool for nanomedicine development and production.

Microfluidic devices are mircoscale fluidic circuits used to manipulate liquids at the nanoliter scale. The ability to control the mixing of fluids and the continuous nature of the process make it apt for solvent/antisolvent precipitation of drug-delivery nanoparticles. This review describes the use of numerous microfluidic designs for the formulation and production of lipid nanoparticles, liposomes and polymer nanoparticles to encapsulate and deliver small molecule or genetic payloads.

Polymeric micelles based on poly(ethylene oxide) and α-carbon substituted poly(ɛ-caprolactone): An in vitro study on the effect of core forming block on polymeric micellar stability, biocompatibility, and immunogenicity.

A series of block copolymers based on methoxy poly(ethylene oxide)-block-poly(ɛ-caprolactone) (PEO-b-PCL), PEO-b-PCL bearing side groups of benzyl carboxylate (PEO-b-PBCL), or free carboxyl (PEO-b-PCCL) on the PCL backbone with increasing degrees of polymerization of the PCL backbone were synthesized. Prepared block copolymers assembled to polymeric micelles by co-solvent evaporation. The physical stability of prepared micelles was assessed by measuring their tendency toward aggregation over time using dynamic light scattering (DLS).

Engineering of amphiphilic block copolymers for polymeric micellar drug and gene delivery.

The use of nano-delivery systems formed through assembly of synthetic amphiphilic block copolymers (ABCs) in experimental medicine and pharmaceutical sciences is experiencing rapid development. This rapid development is driven by a crucial need in improving the performance of existing therapeutic agents, as well as the necessity for the development of advanced delivery systems for complex new entities such as genes, proteins and other cellular components. The flexibility in the construction of appropriate carriers for the delivery requirements of these complex new "drugs" offered by versatile polymer chemistry provides an undeniable advantage for polymer based nano-delivery systems compared to other colloids in this regard.