Table 3.

Considerations for the translational development of nanomedicines.

NANOPHARMACEUTICAL DESIGN

Key Considerations ■ Route of administration ■ Reduce complexity in formulation design ■ Final dosage form for human use ■ Biocompatibility and biodegradability ■ Pharmaceutical stability (physical and chemical)

Current Obstacles

■ Large-scale production according to GMP standards ◦ E.g., Reproducibility, infrastructure, techniques, expertise and cost ■ Quality control assays for characterization ◦ E.g., Size and polydispersity, morphology, charge, encapsulation, surface modifications, purity and stability

PRECLINICAL EVALUATION

Key Considerations ■ Need for validated and standardized assays for early detection of toxicity ■ Evaluation in appropriate animal models of disease ■ Adequate understanding of in vivo behavior, incl. cellular and molecular interactions ◦ Pharmacokinetics (absorption, distribution, metabolism and excretion) ◦ Pharmacodynamics (intracellular trafficking, functionality, toxicity and degradation)

Current Obstacles

■ Development of more specialized toxicology studies for nanomedicines ■ Adequate understanding of the interaction of NNM with tissues and cells ■ Adequate structural stability of NNM following in vivo administration ■ Limited degree of accumulation of nanomedicines in target organs/tissues/cells

CLINICAL EVALUATION FOR COMMERCIALIZATION

Key Considerations ■ Simplification of development pathways from invention to commercialization to minimize time and expense ■ Evaluation of safety/toxicity in humans (acute and chronic) ■ Evaluation of therapeutic efficacy in patients ■ Optimal clinical trial design

Current Obstacles

■ Lack of clear regulatory guidelines specific for NNMs ■ Complexity of NNM patents and IP ■ Limited understanding of the biological interaction of NNM with the biological environment (incl. target site) in the body of patients