A new evidence-based design-of-experiments approach for optimizing drug delivery systems with exemplification by emulsion-derived Vancomycin-loaded PLGA capsules

Abstract

This paper introduces an evidence-based, design-of-experiments (DoE) approach to analyze and optimize drug delivery systems, ensuring that release aligns with the therapeutic window of the medication. First, the effective factors and release data of the system are extracted from the literature and meta-analytically undergo regression modeling. Then, the interaction and correlation of the factors to each other and the release amount are quantitatively assessed. Finally, the factors are numerically and graphically optimized via linking the meta-analyzed release data and the well-documented therapeutic window of the drug, followed by verification. For a more in-depth explanation, the introduced approach is exemplified by a drug delivery, consisting of emulsion-derived poly lactic-co-glycolic acid-vancomycin (PLGA-VAN) capsules for treating Staphylococcus Aureus-induced osteomyelitis. Novel and validated findings for the model system, along with the thorough architecture of the introduced approach, suggest its potential applicability for any delivery systems with sufficient reliable data in the literature.

Keywords: Burst and sustained release kinetics; Local controlled drug delivery systems; Pharmacokinetics.

Fig. 1

Flowchart of the evidence-based DoE optimization approach introduced in this study.

Fig. 2

Demonstrative interaction plots of LA/GA and P/D for BRY (a-d) and TRY (e-h) at MW of 20 (a, e), 30 (b, f), 51 (c, g), and 136 (d, h) kDa in the PLGA-VAN system.

Fig. 3

Demonstrative contours of P/D vs. LA in PLGA (LA/GA) for BRY (a-d) and TRY (e-h) of the model system at MW of 20 (a, e), 30 (b, f), 51 (c, g), and 136 (d, h) kDa. λ is used to show the design points and color-coded terms are in µg/ml.

Fig. 4

Demonstrative surfaces of the model desirability at MW of 20 (a), 51 (b), 120 (c), and 136 (d) kDa for the illustrative PLGA-VAN system. λ is used to show the design points.

Fig. 5

Demonstrative frameworks of the optimal settings at MW of 20 (a), 51 (b), 120 (c), and 136 (d) kDa for the PLGA-VAN system. λ is used to show the design points.