Naturally derived excipients in injectable nanomedicines: a systematic review of pharmacokinetic performance, regulatory readiness, and future quality by design perspectives.
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Abstract
Introduction: Naturally derived excipients such as lecithin, chitosan, and hyaluronic acid offer biocompatibility for injectable nanomedicines, although material variability may limit clinical translation. This systematic review evaluated pharmacokinetic performance alongside regulatory and quality gaps.
Methods: PubMed, Scopus, Web of Science, and Embase (2002-2025) were searched for nanocarriers (≤500 nm) incorporating naturally derived excipients with pharmacokinetic or physicochemical data. Risk of bias was assessed using SYRCLE, Cochrane RoB 2.0, ROBINS-I, and an adapted Newcastle-Ottawa Scale. Descriptive synthesis was performed due to heterogeneity. The protocol was registered on OSF (10.17605/OSF.IO/6XA5M).
Results: Sixty-three studies met inclusion criteria (48 preclinical, 15 clinical). Among preclinical studies reporting pharmacokinetic parameters, median 2.4-fold plasma exposure (n = 15) and 2.9-fold tumor accumulation (n = 18) increases were observed versus free drug. No included studies reported ICH Q8-aligned quality by design (QbD), multivariate modeling, or artificial intelligence. Fewer than 10% reported detailed compositional characterization or impurity profiling relevant to parenteral development.
Conclusions: Naturally derived excipients were associated with pharmacokinetic enhancement, but inconsistent characterization and limited adoption of structured QbD approaches may hinder regulatory translation. Certainty of evidence across outcomes was low, and prospective validation of proposed QbD strategies remains necessary.
期刊介绍：
Delivering therapeutics in a way that is right for the patient - safe, painless, reliable, targeted, efficient and cost effective - is the fundamental aim of scientists working in this area. Correspondingly, this evolving field has already yielded a diversity of delivery methods, including injectors, controlled release formulations, drug eluting implants and transdermal patches. Rapid technological advances and the desire to improve the efficacy and safety profile of existing medications by specific targeting to the site of action, combined with the drive to improve patient compliance, continue to fuel rapid research progress. Furthermore, the emergence of cell-based therapeutics and biopharmaceuticals such as proteins, peptides and nucleotides presents scientists with new and exciting challenges for the application of therapeutic delivery science and technology. Successful delivery strategies increasingly rely upon collaboration across a diversity of fields, including biology, chemistry, pharmacology, nanotechnology, physiology, materials science and engineering. Therapeutic Delivery recognizes the importance of this diverse research platform and encourages the publication of articles that reflect the highly interdisciplinary nature of the field. In a highly competitive industry, Therapeutic Delivery provides the busy researcher with a forum for the rapid publication of original research and critical reviews of all the latest relevant and significant developments, and focuses on how the technological, pharmacological, clinical and physiological aspects come together to successfully deliver modern therapeutics to patients. The journal delivers this essential information in concise, at-a-glance article formats that are readily accessible to the full spectrum of therapeutic delivery researchers.
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