Nanomedicines: From Bench to Bedside and Beyond.

Advancing nanomedicines from concept to clinic requires integration of new science with traditional pharmaceutical development. The medical and commercial success of nanomedicines is greatly facilitated when those charged with developing nanomedicines are cognizant of the unique opportunities and technical challenges that these products present. These individuals must also be knowledgeable about the processes of clinical and product development, including regulatory considerations, to maximize the odds for successful product registration. This article outlines these topics with a goal to accelerate the combination of academic innovation with collaborative industrial scientists who understand pharmaceutical development and regulatory approval requirements-only together can they realize the full potential of nanomedicines for patients.

Nanomedicine drug development: a scientific symposium entitled "Charting a roadmap to commercialization".

The use of nanotechnology in medicine holds great promise for revolutionizing a variety of therapies. The past decade witnessed dramatic advancements in scientific research in nanomedicines, although significant challenges still exist in nanomedicine design, characterization, development, and manufacturing. In March 2013, a two-day symposium "Nanomedicines: Charting a Roadmap to Commercialization," sponsored and organized by the Nanomedicines Alliance, was held to facilitate better understanding of the current science and investigative approaches and to identify and discuss challenges and knowledge gaps in nanomedicine development programs. The symposium provided a forum for constructive dialogue among key stakeholders in five distinct areas: nanomedicine design, preclinical pharmacology, toxicology, CMC (chemistry, manufacturing, and control), and clinical development. In this meeting synopsis, we highlight key points from plenary presentations and focus on discussions and recommendations from breakout sessions of the symposium.

Preclinical to clinical development of the novel camptothecin nanopharmaceutical CRLX101.

Camptothecin (CPT) is a potent broad-spectrum anticancer agent that acts through inhibition of topoisomerase 1. Clinical development of CPT was unsuccessful due to poor drug solubility, insufficient in vivo stability of the active form, and toxicity. In order to address these issues, a polymeric nanoparticle comprised of cyclodextrin-poly(ethylene glycol) copolymer (CDP) conjugated to CPT (CRLX101) has been developed and Phase 2 clinical studies are ongoing. Camptothecin is conjugated to the polymer in its active form at 10-12 wt.% loading. CRLX101 self-assembles in solution into nanoparticles with an apparent solubility increase of >1000-fold as compared to the parent drug camptothecin. Preclinical studies exhibited CRLX101 pharmacokinetics superior to the parent drug. Drug concentration in tumor relative to plasma and other major organs is consistent with the enhanced permeation and retention (EPR) anticipated from a nanoparticle. Significant anti-tumor activity was observed that is superior when compared to irinotecan across a broad range of xenograft models. Pharmacokinetic data are consistent with the prolonged half-life and increased AUC. The CRLX101 preclinical and clinical data confirm that CDP can address not only solubility, formulation, toxicity, and pharmacokinetic challenges associated with administration of CPT, but more importantly, can impart unique biological properties, that enhance pharmacodynamics and efficacy of camptothecin.