ENHANCING BIOAVAILABILITY THROUGH NANOTECHNOLOGY: A META-ANALYSIS OF LIPOSOMAL FORMULATIONS AND IN VITRO VALIDATION FRAMEWORKS

Oral administration remains a major challenge for numerous bioactive compounds because poor aqueous solubility, chemical instability, limited intestinal permeability, gastrointestinal degradation, and extensive presystemic metabolism can substantially restrict systemic exposure. Liposomal delivery systems have emerged as a promising strategy to address several of these limitations by incorporating active compounds within phospholipid-based vesicles that can improve gastrointestinal stability, dispersion, and absorption. However, the magnitude and consistency of pharmacokinetic enhancement across different liposomal formulations require systematic evaluation. This review and meta-analysis synthesized clinical evidence from 18 randomized controlled human trials involving 412 healthy adult participants to evaluate the effects of oral liposomal formulations on pharmacokinetic outcomes, particularly maximum plasma concentration (Cmax), area under the concentration–time curve (AUC), time to maximum concentration (Tmax), and terminal elimination half-life (t1/2). Across the included studies, liposomal formulations generally produced higher systemic exposure than corresponding non-liposomal controls. Reported increases in Cmax ranged from approximately 1.2- to 5.4-fold, while AUC improvements ranged from approximately 1.3- to 7.2-fold, although substantial variability was observed among active ingredients and formulations.[3,5,11,13,20] Hydrophobic compounds such as curcumin, CoQ10, and resveratrol generally demonstrated greater pharmacokinetic enhancement than hydrophilic nutrients, whereas liposomal mineral formulations showed moderate but measurable improvements in systemic or intracellular exposure.[4, 14, 21, 24, 26] In addition to clinical pharmacokinetic evidence, the review considers the relevance of physicochemical and in vitro characterization parameters, including particle size, polydispersity index, encapsulation efficiency, gastrointestinal stability, release behavior, and cellular viability. The Lipoedge™ framework provides an integrated approach for evaluating these formulation attributes and may support formulation development, quality assessment, and batch-to-batch consistency.[10,32,33] Importantly, in vitro characterization should be considered complementary to, rather than a replacement for, human pharmacokinetic evaluation. Overall, the available evidence supports oral liposomal delivery as a potentially effective strategy for improving systemic exposure to selected bioactive compounds, while emphasizing the importance of payload-specific formulation optimization, standardized characterization, and further clinical validation.

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