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Critical quality attributes in the development of therapeutic nanomedicines toward clinical translation

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Abstract

Nanomedicine is a rapidly emerging field with several breakthroughs in the therapeutic drug delivery application. The unique properties of the nanoscale delivery systems offer huge advantages to their payload such as solubilization, increased bioavailability, and improved pharmacokinetics with an overall goal of enhanced therapeutic index. Nanomedicine has the potential for integrating and enabling new therapeutic modalities. Several nanoparticle-based drug delivery systems have been granted approval for clinical use based on their outstanding clinical outcomes. Nanomedicine faces several challenges that hinder the realization of its full potential. In this review, we discuss the critical formulation- and biological-related quality features that significantly influence the performance of nanoparticulate systems in vivo. We also discuss the quality-by-design approach in the pharmaceutical manufacturing and its implementation in the nanomedicine. A deep understanding of these nanomedicine quality checkpoints and a systematic design that takes them into consideration will hopefully expedite the clinical translation process.

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Abbreviations

ADCs:

Antibody-drug conjugates

AuNPs:

Gold nanoparticles

BBB:

Blood-brain barrier

BxPC3:

Human pancreatic cancer cell line

cGMP:

Current good manufacturing practice

CNS:

Central nervous system

C26:

Colon adenocarcinoma

CMAs:

Critical material attributes

CPPs:

Critical process parameters

CQAs:

Critical quality attributes

CS:

Control strategy

DoE:

Design of experiment

DP:

Drug product

DS:

Design space

EPR:

Enhanced permeation and retention

FDA:

Food and Drug Administration

FMEA:

Failure mode and effect analysis

GSH:

Glutathione

HER-2:

Human epidermal growth factor receptor 2

ICH:

International Conference of Harmonization

MPS:

Mononuclear phagocytic system

PAT:

Process analytical technology

PEG:

Polyethylene glycol

PK:

Pharmacokinetics

PLGA:

Poly (lactic-co-glycolic acid)

QbD:

Quality-by-design

QTPP:

Quality target product profile

RES:

Reticuloendothelial system

siRNA:

Small interfering RNA

SNEDDS:

Self-nanoemulsifying drug delivery systems

TAMs:

Tumor-associated macrophages

TPP:

Target product profile

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, School of Pharmacy, Northeastern University, 360 Huntington Avenue, Boston, MA, 02115, USA

    Maie S. Taha, Smrithi Padmakumar & Mansoor M. Amiji

  2. Massachusetts Eye and Ear Infirmary, Harvard Medical School, 243 Charles Street, Boston, MA, 02114, USA

    Maie S. Taha

  3. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Maie S. Taha

  4. Puretech Health, 6 Tide Street, Boston, MA, 02210, USA

    Amit Singh

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Taha, M., Padmakumar, S., Singh, A. et al. Critical quality attributes in the development of therapeutic nanomedicines toward clinical translation. Drug Deliv. and Transl. Res. 10, 766–790 (2020). https://doi.org/10.1007/s13346-020-00744-1

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