Coating Materials to Increase the Stability of Liposomes

**Background:** Liposomes are artificial spherical nanostructures composed of phospholipid bilayers, widely used as delivery systems for drugs, nutraceuticals, and food ingredients due to their biocompatibility and encapsulation capacity. However, their application is limited by poor physical and chemical stability—susceptibility to oxidation, hydrolysis, temperature, light, and pH changes—which leads to premature leakage and degradation of encapsulated compounds. Coating liposomes with various materials can protect the lipid membrane, extend circulation time, and enable targeted release. This narrative review summarizes current knowledge on coating materials for liposomes with applications in pharmaceuticals and food, focusing on their influence on stability and absorption.

**Methods:** The authors conducted a literature review of studies on liposome coating materials, including saccharides (chitosan, alginate, pectin, starch, gums, inulin, hyaluronic acid), polymers (PEG, poly(L-lysine), Eudragit EPO), proteins (whey protein, albumin, zein, silk fibroin, gelatin, collagen), and combinations thereof. They also reviewed physical and chemical factors affecting liposome stability (temperature, light, pH, lipid peroxidation) and discussed in vitro and in vivo digestion, absorption mechanisms, and clinical trials. Data were extracted from tables summarizing stability measurements, coating materials, and commercial products.

**Key Results:** Physical factors: Storage temperature significantly affects stability; for example, betacyanin-loaded liposomes showed retention rates of 75.54% at 4°C, 67.57% at 25°C, and 20.28% at 37°C over 21 days. UV irradiation caused degradation of 25.841% (UV-A), 32.881% (UV-B), and 35.678% (UV-C) for small unilamellar vesicles. Chemical factors: pH variations reduced stability; at pH 3, retention rate was 50% compared to 80% at pH 5–7 for betacyanin liposomes. Coating materials improved stability: chitosan-coated liposomes enhanced bioactivity, bioavailability, and delayed release in simulated gastrointestinal digestion. PEG coating increased circulation time and reduced RES clearance, but may cause immune responses. Pectin-coated liposomes improved long-term release and system stability. Whey protein coating improved thermal and light stability of astaxanthin liposomes. Inulin-coated liposomes showed better stability in surfactants and electrolytes. Clinical trials include liposomal bupivacaine (DepoFoam technology) with 96 h duration of action versus 8–9 h for normal bupivacaine, and PEG-coated doxorubicin (2B3-101) for meningeal carcinomatosis (Phase II). Commercial products: Doxil (doxorubicin), AmBisome (amphotericin B), and numerous liposomal supplements (vitamin C, D3, glutathione, curcumin) are on the market.

**Clinical Implications:** Coated liposomes offer a promising strategy to overcome stability limitations, enabling targeted and controlled release of active compounds. In pharmaceuticals, PEGylation remains common but alternatives (e.g., natural polysaccharides, proteins) are being explored to avoid immune reactions. In the food industry, saccharide and protein coatings improve stability during processing and digestion, though few commercial food products exist. Future research should focus on developing new coating materials, optimizing industrial production, and expanding applications to solid food products. The review highlights the need for economically efficient, non-toxic coating methods to enhance liposome shelf life and performance.