What are lipid nanovesicles and how are they utilized in skin‑care products?

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Lipid Nanovesicles in Skin Care Products

Lipid nanovesicles are nanoscale (1-1000 nm) biodegradable delivery systems composed of phospholipid bilayers that encapsulate both water-soluble and fat-soluble active ingredients, functioning in skin care products primarily as penetration enhancers and controlled-release carriers for cosmetic actives. 1

What Are Lipid Nanovesicles?

Core Structure and Composition

  • Lipid nanovesicles consist of phospholipid bilayers with amphiphilic properties (hydrophobic tails and hydrophilic heads) that spontaneously form closed vesicular structures in aqueous environments 1

  • The dual-compartment architecture allows simultaneous delivery of both hydrophilic actives (trapped in the aqueous core) and lipophilic actives (embedded within the lipid bilayer) 1

  • Primary phospholipids used include phosphatidylcholines (DMPC, DPPC, DSPC, DOPC), phosphatidylethanolamines, and phosphatidylglycerols, with cholesterol (0-25% w/w) added as a stabilizing agent 1

Classification by Structure

Unilamellar vesicles contain a single bilayer with one aqueous core and are subdivided into:

  • Small unilamellar vesicles (SUV): <100 nm diameter, spherical with limited hydrophilic drug capacity 1
  • Large unilamellar vesicles (LUV): 100-1000 nm, with larger aqueous cores for enhanced hydrophilic molecule encapsulation 1

Multilamellar vesicles (MLV) feature multiple concentric bilayers (nanometric to 1 μm), offering higher drug entrapment efficiency when bilayers number less than 4 (oligolamellar vesicles) 1

Classification by Surface Charge

  • Anionic lipid vesicles demonstrate superior penetration through the stratum corneum 1
  • Cationic liposomes provide improved storage stability by preventing aggregation through electrostatic repulsion 1
  • Neutral vesicles offer baseline delivery without charge-related interactions 1

How They Function in Skin Care Products

Mechanisms of Skin Interaction

Conventional liposomes do not penetrate intact through skin layers but remain on the stratum corneum surface, functioning through four distinct mechanisms 1:

  1. Depot formation with "collision complex transfer" where vesicles exchange contents with skin surface components 1
  2. Free drug release from disrupted vesicles that then penetrates independently 1
  3. Structural modification of stratum corneum lipids to facilitate absorption 1
  4. Insertion into outer lipid layers of the stratum corneum without intact vesicle penetration 1

Critical caveat: Imaging studies using stimulated emission depletion microscopy confirm that liposomes do not remain structurally intact beneath the skin surface, contradicting earlier assumptions about direct carrier transport 1

Advanced Formulations for Enhanced Skin Delivery

Transfersomes (Ultraflexible Vesicles)

  • Incorporate edge activators (surfactants like Tween®, Span®, bile salts) at 15% w/w for non-ionic surfactants or 25% w/w for sodium deoxycholate 1
  • Edge activators destabilize lipid bilayers, increasing fluidity and elasticity by lowering interfacial tension, enabling deformation through pores smaller than vesicle diameter 1, 2
  • Mechanism differs from conventional liposomes: elasticity rather than fluidity drives penetration 2

Ethosomes

  • Contain high ethanol concentrations (20-30% w/w optimal, up to 50% possible) combined with phospholipids 1
  • Ethanol fluidizes phospholipid bilayers, creating soft vesicles that penetrate deeper into skin layers 2
  • Size decreases with increasing ethanol concentration, affecting delivery characteristics 1

Glycerosomes and Propylene Glycol-Liposomes

  • Incorporate 10-30% glycerol or propylene glycol in the aqueous phase 1
  • Dual function: confer bilayer flexibility while simultaneously hydrating skin through glycerol's humectant properties 1
  • Glycerol intercalates into the lipid bilayer, as confirmed by differential scanning calorimetry and ATR-FTIR studies 3

Skin Penetration Enhancer-Incorporated Lipid Nanovesicles (SPE-LNV)

  • Ceramide and fatty acid incorporation enables transdermal delivery of highly water-soluble actives like niacinamide and adenosine 4
  • SPE-LNV interact with stratum corneum constituents, facilitating permeation of otherwise poorly penetrating hydrophilic molecules 4
  • Formulations containing both ceramide and fatty acids demonstrate deeper penetration depth and faster permeation rates compared to conventional lipid nanovesicles 4

Hyaluronosomes

  • Feature a gelled hyaluronic acid nucleus providing controlled release without the excessive retention or stability issues of polymeric matrices 1

Practical Applications in Skin Care

Delivery Advantages

  • Enhanced stability of photosensitive molecules during storage and application 1
  • Reduced degradation of active ingredients through protective encapsulation 1
  • Depot release mechanism for sustained delivery over time 1
  • Improved solubilization of poorly water-soluble cosmetic actives 1, 2

Clinical Evidence for Efficacy

  • In vivo clinical trials with ceramide-fatty acid lipid nanovesicles demonstrate substantial decreases in melanin index and skin wrinkle measurements compared to controls 4
  • Polyoliposomes (glycerol-modified vesicles) show significantly higher entrapment efficiency and deformability index than conventional liposomes, with confirmed enhanced ex vivo and in vivo skin permeation 3

Common Pitfalls to Avoid

  • Excessive cholesterol content (>25% w/w) reduces lipophilic drug entrapment by occupying bilayer space and increases vesicle size/polydispersity 1
  • Higher cholesterol increases bilayer rigidity, reducing flexibility and potentially limiting skin interaction 1
  • Surfactant concentrations exceeding critical micelle concentration lead to micelle formation rather than vesicle incorporation, negating penetration enhancement 1
  • Surface-decorated vesicles with targeting ligands hinder passive transdermal diffusion, making them unsuitable for topical applications despite advantages in parenteral delivery 1

Optimal Formulation Parameters

  • Phospholipid/cholesterol ratio: 0-25% w/w cholesterol depending on desired rigidity and drug type 1
  • Edge activator concentration: 15% w/w for non-ionic surfactants (Tween®, Span®) or 25% w/w for sodium deoxycholate 1
  • Ethanol concentration: 20-30% w/w for closed multilamellar ethosomes with optimal transdermal delivery 1
  • Glycerol/propylene glycol: 10-30% in aqueous phase for flexibility and hydration 1

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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