European Journal of Biomedical and Pharmaceutical Sciences

IN-VITRO STUDIES OF LIPOSOMAL ?-LIPOIC ACID: FORMULATION STRATEGIES, PHYSICOCHEMICAL CHARACTERIZATION, RELEASE BEHAVIOR, ANTIOXIDANT ACTIVITY, CELLULAR INTERACTIONS AND THERAPEUTIC POTENTIAL

Dr. Poulami Gupta Banerjee*, Ranita Roy, Dr. Priyanka Bhattacharyya, Dr. Sayoni Maitra Roy, Riya Halder

ABSTRACT

α-Lipoic acid (ALA), also known as thioctic acid, is a naturally occurring organosulfur compound that functions as a cofactor in mitochondrial oxidative metabolism and possesses broad antioxidant and redox-regulatory properties. Both ALA and its reduced metabolite, dihydrolipoic acid (DHLA), participate in the regulation of reactive oxygen species, regeneration of endogenous antioxidants and maintenance of cellular redox homeostasis. Despite these pharmacological advantages, the therapeutic and nutraceutical application of ALA is constrained by limited aqueous solubility, rapid systemic elimination, extensive first-pass metabolism and formulation-dependent bioavailability. Liposomal delivery represents a potentially attractive strategy for overcoming several of these limitations because phospholipid vesicles can incorporate amphiphilic molecules within or near the lipid bilayer, protect labile compounds from environmental degradation and facilitate interactions with biological membranes. The present review critically examines the available in-vitro evidence for liposomal ALA, with emphasis on formulation development, lipid composition, preparation techniques, physicochemical characterization, encapsulation efficiency, structural organization, stability, release kinetics, antioxidant activity, cellular uptake, cytocompatibility, membrane interactions and application-specific performance. Evidence from conventional liposomes, chitosan-coated liposomes, phosphatidylcholine-based nanoforms and functional hybrid liposomes is discussed, while solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions and lipid nanocapsules are considered primarily for comparison. Published studies demonstrate that liposomal incorporation can modify the physicochemical behavior of ALA, promote sustained release in selected systems, enhance antioxidant performance and facilitate cellular delivery. Particularly promising findings have been reported for chitosan-coated ALA/CoQ10 liposomes, which demonstrated sustained release and enhanced skin accumulation, and for phosphatidylcholine/gelatin-curcumin hybrid liposomes, which showed rapid cellular uptake and prolonged ALA retention. A 2025 liposomal formulation designed for ocular administration further demonstrated enhanced DPPH radical-scavenging activity and cytocompatibility in human conjunctival epithelial cells. However, the evidence base remains fragmented, with considerable heterogeneity in lipid composition, particle size, analytical methods, loading approaches, release media and biological models. Moreover, direct comparisons between free ALA and equivalent-dose liposomal ALA remain limited. Future research should therefore prioritize standardized characterization, mechanistic cellular studies, physiologically relevant release models, quantitative uptake studies, long-term stability, scalable manufacturing and comparative pharmacokinetic evaluation. Collectively, current in-vitro evidence supports liposomal ALA as a promising formulation platform, but additional systematic investigation is required before definitive conclusions regarding superior bioavailability or clinical efficacy can be established.

Keywords: ?-lipoic acid; thioctic acid; liposomes; lipid nanocarriers; antioxidant; oxidative stress; drug delivery; encapsulation; controlled release; cellular uptake; in-vitro studies; nanomedicine.