Developability assessment for monoclonal antibody drug candidates: a case study.

Various screening approaches are used by industry to evaluate development risks associated with discovery candidates. This process has become more complicated with biological therapeutics, a class dominated by monoclonal antibodies (mAb), and, increasingly, their derivative constructs. Effective early assessment for drug-like properties (DLP) can save time and costs by allowing a more complete consideration of issues that could impact the desired end result of a stable drug product.

Investigation of Fragment Antibody Stability and Its Release Mechanism from Poly(Lactide-co-Glycolide)-Triacetin Depots for Sustained-Release Applications.

Achieving long-term drug release from polymer-based delivery systems continues to be a challenge particularly for the delivery of large hydrophilic molecules such as therapeutic antibodies and proteins. Here, we report on the utility of an in situ-forming and injectable polymer-solvent system for the long-term release of a model antibody fragment (Fab1). The delivery system was prepared by dispersing a spray-dried powder of Fab1 within poly(lactide-co-glycolide) (PLGA)-triacetin solution.

Drug release from a pH-sensitive multiblock co-polymer thermogel.

A Pluronic(®)-based pH-sensitive multiblock co-polymer thermogel has been proposed for sustained release of therapeutic agents. Hydrophobic small-molecule drugs (paclitaxel and camptothecin) and model hy-drophilic macromolecules (fluorescein-labeled dextrans of molecular mass 10, 20, 40, 150 and 250 kDa) were successfully loaded into and released from the thermogels. Drug-loaded polymer solutions were characterized for gelation behavior and micelle size.

Matrix metalloproteinase-sensitive thermogelling polymer for bioresponsive local drug delivery.

Development of a successful bioresponsive drug delivery system requires exquisite engineering of the materials so that they are able to respond to signals stemming from the physiological environment. In this study we propose a new Pluronic(®) based thermogelling system containing matrix metalloproteinase-2 (MMP2) responsive peptide sequences. A novel thermosensitive multiblock co-polymer comprising an MMP2-labile octapeptide (Gly-Pro-Val-Gly-Leu-Ile-Gly-Lys) was synthesized from a Pluronic(®) triblock co-polymer.

Novel pH-sensitive polyacetal-based block copolymers for controlled drug delivery.

The principal aim of this study was to synthesize and characterize pH-sensitive biodegradable triblock copolymers containing a hydrophobic polyacetal segment for controlled drug delivery. Poly(ethylene glycol)-poly(ethyl glyoxylate)-poly(ethylene glycol) (PEG-PEtG-PEG) triblock copolymers with PEG molecular weights 500 (PEtG-PEG(500)) and 750 (PEtG-PEG(750)) were synthesized by PEtG end-capping with methoxy PEG via a carbamate linkage. Synthesized amphiphilic PEG-PEtG-PEG was characterized by (1)H NMR spectroscopy.

A thermosensitive vaginal gel formulation with HPgammaCD for the pH-dependent release and solubilization of amphotericin B.

To achieve better therapeutic efficacy and patient compliance in the treatment for Candida vaginitis, the antifungal agent amphotericin B (AmB) was formulated in a vaginal gel using Pluronic-based multiblock copolymers (MBCP-2). To increase its aqueous solubility, the drug was incorporated as its inclusion complex with hydroxypropyl-gamma-cyclodextrin (HPgammaCD). The formation of the AmB inclusion complex was characterized using different techniques including XRD, FT-IR spectrophotometry, DSC, and SEM.