What are phospholipids, their clinical applications, recommended dosing, and contraindications?

Phospholipids: Structure, Clinical Applications, and Therapeutic Use

What Are Phospholipids?

Phospholipids are amphipathic molecules consisting of a hydrophilic headgroup and two hydrophobic acyl tails that serve as the fundamental structural components of all cell membranes, organized as lipid bilayers. 1, 2

• Phospholipids belong to the glycerol-derived lipid class, showing structural similarity to triglycerides but with distinct functional properties 3
• The amphiphilic character results from hydrophobic tails and hydrophilic heads, allowing spontaneous dispersion in aqueous media 1
• Common types include phosphatidylcholines (DMPC, DPPC, DSPC, DOPC), phosphatidylethanolamines (DMPE, DPPE, DSPE, DOPE), phosphatidylglycerols (DPPG, DSPG, POPG), and phosphatidic acids (DMPA, DPPA, DSPA) 1

Structural and Functional Roles

• Phospholipids maintain membrane integrity as hydrophobic barriers while simultaneously serving regulatory functions in signaling pathways 4
• They incorporate both hydrophilic and lipophilic compounds within their bilayer structure 1
• Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol are the main structural lipids in cell membranes 1
• Variations in polar head and nonpolar tail functional groups create diverse phospholipid types that condition membrane properties differently 1

Clinical Applications in Drug Delivery

Phospholipid-based vesicles (liposomes, transfersomes, ethosomes) are non-toxic and biodegradable drug carriers that enhance transdermal drug delivery, improve penetration of poorly soluble drugs, and provide controlled release. 1

• The lipophilic nature allows incorporation of poorly water-soluble drugs and improves skin penetration properties 1
• Additional benefits include increased stability of photosensitive molecules, lower drug degradation, and depot release 1
• Phospholipid/cholesterol ratios typically vary from 0 to 25% w/w depending on application purposes 1

Formulation Considerations

• Higher cholesterol content increases vesicle size and rigidity but decreases entrapment efficiency of lipophilic drugs 1
• Phosphatidylcholines form permeable but less stable bilayers, whereas acyl chain-based phospholipids form more stable but rigid structures 1
• Edge-activators (surfactants like tweens, spans, bile salts) at 15% w/w for non-ionic surfactants or 25% w/w for sodium deoxycholate optimize transdermal delivery 1

Therapeutic Benefits and Health Effects

Dietary phospholipids demonstrate positive impacts in multiple disease states by delivering fatty acid residues for incorporation into cell membranes, thereby altering membrane composition and affecting receptor activity. 3, 5

• Phospholipids show effectiveness in inflammatory processes, cancer, cardiovascular diseases, neurological disorders, and liver disease 3
• They exhibit better absorption and utilization than triglycerides for incorporating different fatty acids into cell membranes 3
• Phospholipids reduce side effects of certain drugs and appear to lack severe adverse effects themselves 5

Mechanism of Action

• Altered membrane composition affects activity of membrane proteins and receptors by modifying lipid raft microstructure 5
• Phospholipids influence biosynthesis of fatty acid-derived lipid second messengers 5
• The fatty acid composition of the phospholipid determines its therapeutic effect, making the phospholipid source (soy, egg yolk, milk, marine) crucial 5

Cardiovascular Applications

• Long-chain n-3 PUFA in phospholipids of erythrocyte membranes (omega-3 index >6.8%) inversely associate with total cardiovascular events (RR 0.61; 95% CI 0.37,0.99) 1
• Higher plasma phospholipid concentrations of EPA+DHA reduce myocardial infarction mortality (RR 0.23; 95% CI 0.12,0.76) 1
• The omega-3 index (sum of EPA+DHA/total fatty acids in phospholipids of erythrocyte membranes) in the highest tertile associates with lower CHD mortality (RR 0.78; 95% CI 0.64,0.95) 1

Dosing and Administration

For cardiovascular prevention, EPA plus DHA at 460 mg EPA + 380 mg DHA daily demonstrates significant reduction in CHD mortality (RR 0.81; 95% CI 0.67,0.99) in diabetic patients. 1

• In primary prevention trials, 460 mg EPA + 380 mg DHA daily reduces total myocardial infarction (RR 0.72; 95% CI 0.59,0.90) and fatal MI (RR 0.50; 95% CI 0.26,0.97) 1
• For transdermal drug delivery systems, phospholipid concentrations depend on the specific application and drug being delivered 1

Contraindications and Precautions

• Phospholipids in bile provide protective effects to intestinal cells, but high concentrations of bile salts (>15 mM sodium taurocholate) combined with low pH (5.0) cause cellular toxicity even with phospholipid presence 1
• Lecithin at 1.5 mM protects cells from permeability damage caused by 5 mM sodium taurocholate, but this protective effect has limits 1
• The fatty acid composition of supplemented phospholipids is crucial—inappropriate fatty acid profiles may not provide intended benefits 5

Clinical Monitoring in Specific Conditions

• In systemic lupus erythematosus, anti-phospholipid antibodies require baseline measurement and re-evaluation prior to pregnancy, surgery, transplant, or with new neurological/vascular events 1
• Anti-phospholipid antibodies should be monitored in lupus nephritis patients, especially those with nephrotic syndrome and serum albumin <20 g/L 1
• Testing for lupus anticoagulant (which detects phospholipid-dependent antibodies) should use double centrifugation and fresh venous blood in 0.109 M sodium citrate 1

Common Pitfalls

• Do not assume all phospholipid sources provide equivalent benefits—marine, soy, egg yolk, and milk phospholipids have different fatty acid compositions and thus different effects 5
• Avoid using phospholipid formulations with excessive cholesterol content when delivering lipophilic drugs, as they compete for the same bilayer space 1
• Most evidence for phospholipid supplementation benefits comes from in vitro or animal studies; human clinical evidence remains limited 5