The Liposome Advantage – ALIVE BY SCIENCE – Bioavailable NAD+ Boosters

The Liposome Advantage

 

Liposomes are a revolutionary way of encapsulating active ingredients to protect and deliver them directly to the cells of our tissues, which are reached via the bloodstream. 1

Liposomes stabilize therapeutic compounds—overcoming obstacles to cellular and tissue uptake—and improve the biodistribution of compounds to target sites.

 

Solves the Bioavailibility Problem

The aim of taking any supplement is to ensure its transport into the bloodstream via the mucosal and intestinal epithelial cells.

However, due to low absorption and bioavailability rates of traditional oral dietary capsules, active ingredients lose most of their potency while passing through the gastrointestinal tract or are simply not absorbed in the small intestine at all. The majority is excreted unused via the intestines or kidneys. 2

Liposomes are vesicles comprised of phospholipids—the primary building blocks of cell membranes. Because they are made of the same material our cell membranes are made of, as they bond to these membranes, they facilitate the delivery of nutrients that are difficult for your body to absorb.

 

Targeted Delivery

Liposomal delivery offers a targeted and complete absorption of active ingredients with a delayed‑release effect, unlike all other nutrient delivery methods. This increased circulation time of key nutrients in the bloodstream significantly bioavailability. The higher the bioavailability of an active substance, the more effect it has on the body. 3

 

Advanced Absorption

Liposomes are absorbed through the oral mucosal lining and through lymphatic mechanisms in the gut, bypassing first pass metabolism and breakdown in the liver ensuring the retention of liposome integrity. A synthesis takes place which allows vitamins, minerals or micronutrients to be transported more easily. This higher absorption, means greater efficacy and with smaller doses needed to achieve better results. 4

 

Biocompatibility

Phospholipids, which are found throughout the body in the membranes of body cells, are so naturally-occurring, that the body recognizes these as body-compatible and does not treat them as ‘toxic’ or ‘foreign’—and, so, does not mount an immune attack on the liposome. 5

 

Masking

Liposomes shield nutrients from detection by the body’s immune system, mimicking biological membranes and giving the active ingredients more time to reach their intended destination.  

Phospholipids mask the active ingredients so that larger amounts can be absorbed and escape the selective function of the small intestine. Osmotic (hydrophilic) side effects of some high-dose vitamins and minerals can thus be reduced. 6

 

Crosses the Blood Brain Barrier

Liposomes have demonstrated the ability to cross this barrier, giving the liposomes the ability to deposit the supplement directly into the cells and enhance circulation of nutrients by your lymphatic system. 7

 

Nanoscale Power

This profound effect of liposome size on complement recognition can also affect liver uptake. Generally, large unmodified liposomes are eliminated more rapidly than small liposomes, which is why our Fluidizing Liposomes™ are very small—less than 100 nm to prevent their uptake by macrophages of the liver and the spleen. 8

 

What are Liposomes made of?

The word liposome comes from the Greek words ‘lipo’ for fat and ‘soma’ for body.  Liposomes are spherical ‘sacs’ consisting of a double ring of fatty-acid molecules—phosphatidylcholine molecules (phospholipid attached to a choline particle).

The liposomal spherical ‘sac’ can be used to enclose and deliver contents of the ‘sac’ directly into the cells and body tissues.

The phospholipid molecule consists of a hydrophilic phosphate head and two hydrophobic fatty acid tails. This enables liposomes to be carriers of both hydrophobic and hydrophilic compounds. Liposomes are lipid vesicles made of phospholipids strung together, which form a double membrane, just like almost all cell membranes of our body.

The encapsulation of hydrophilic or hydrophobic nutrients within liposomes, such as NMN, allows the active ingredient to bypass the destructive elements of the gastric system. improved its oral bioavailability and increase peak plasma concentration. 9

 

What does phosphatidylcholine do?

Phosphatidyl­choline is required for many vital functions in the cardiovascular, reproductive, immune, and nervous systems. PC and its components are needed for the synthesis of important messenger molecules called prostaglandins which, among other functions, regulate the contraction and relaxation of muscles. Choline is required for the synthesis of intracellular messenger molecules including the neurotransmitters that allow nerve cells to communicate with muscles and each other, and are essential for proper heart and brain function.

At birth up to 90% of cellular membranes are made up of PC. As you age, the percentage of PC in your cellular membranes can decrease to about 10%. This fact leads many to recommend consistent supplementation with this essential phospholipid. 10

 

How do Liposomes work?

Liposomes release bioactive nutrients by membrane fusion. They delay the clearance and increase the intravascular circulation time of encapsulated nutrients and prolonging retention time.

At the first stage of liposome-cell interaction, liposomes adhere to the cell surface. Following such binding, the liposome is internalized into the cell by the mechanism of endocytosis (or phagocytosis). This is followed by the enzymatic digestion of the liposome in the intracellular compartment, accompanied by the intracellular distribution.

The active nutrient encapsulated in the liposome is protected from metabolism and the molecule becomes active only after release from liposome.

These encapsulating phospholipids bond with cell membranes to facilitate intracellular delivery. They are successful in this because they are able to bypass the digestive processes that normally degrade foreign substances.

Liposomes ensure safe delivery of encapsulated cargo retain it in tissues and cells.

 

References

1.  Potential of Liposomes for Enhancement of Oral Drug Absorption

2.  Nanocarriers for oral drug delivery

3.  Composition design and medical application of liposomes

4.  Liposomal Delivery Systems: Design Optimization and Current Applications

5.  Oral Bioavailability: Issues and Solutions via Nanoformulations

6.  Spontaneous In Situ Formation of Liposomes from Inert Porous Microparticles for Oral Drug Delivery

7.  Stabilization of liposomes during drying

8.  Powdered lipid nano and microparticles: production and applications. Lipid nanoparticles as vehicles for macromolecules: nucleic acids and peptides

9.  Scalable solvent-free production of liposomes

10.  Membrane lipids: where they are and how they behave

Key Advantages of Liposomal Delivery:

  • Protects against the harsh environment of the GI tract and increases transmucosal (oral) uptake and absorption.
  • Optimizes both hydrophilic and hydrophobic, unstable compounds.
  • Timing of the dose does not require accompaniment or exclusion of food as the absorption via the liposome avoids the digestive processes.
  • Provides a larger nutrient payload per particle.
  • Offers higher bioavailability and absorption compared to conventional capsules.
  • Increases increase peak plasma concentration.
 

Research on Lipsomes for increased bioavailability

Liposomes protect products from digestion in the GI tract, but that is only the first step. The improved bioavailability varies greatly, depending on the molecule itself and the quality of the liposome. Water solubility. Molecules with very poor water solubility usually have the worst bioavailability and can benefit the most from liposomal delivery. Fisetin is one example shown below up to 27x more bioavailable. Liposome Stability. Liposomes need modification to increase stability so they do not break apart and release their payload when exposed to the GI tract and bloodstream. Recent advances in Liposomal technology enables skilled manufacturers to adjust the stability so the payload is protected for several hours. Different manufacturing techniques result in significant variation in stability and bioavailability. Liposome size. As noted above, size of the liposome is crucial. Larger Lipsomes are quickly filtered out by the liver and other parts of the RES. Smaller liposomes (below 50 nanometers) can circulate much longer. The study on B-12 below shows the larger size liposome formula increased bioavailability of 3xvs 5x for the smaller sized liposomal formula.

Liposomal Fisetin 1.6 to 27x more bioavailable

This study in mice found a 2.7-fold increase (in Cmax) with Liposomal Fisetin, with a dose 10 times lower than that of the free fisetin when given by IP.   With IV, the Cmax of liposomal fisetin was 10, vs 6 for free fisetin.  

Liposomal Vitamin B-12 formulas 3-5x more bioavailable than tablet.

Route and Type of Formulation Administered Influences the Absorption and Disposition of Vitamin B12 Levels in Serum This study compared five formulations for bioavailabilty in humans over 6 hours.A standard table (iii) was compared against an emulsion (ii), a chewabletablet (iv), an oral spray comprised of larger liposomes (v) and an oral spray comprised of very small (20 nanometer) liposomes.
(i)Nanocelle 1000ug -28% - A nano liposomal formulation of B12sublingual spray with an average particle size of about 20 nm
(ii) Emulsion 1000ug - 10% -An emulsion formulation of B12 sublingual (iii) Tablet 1000ug - 5% - A standard tablet formulation of B12 that is absorbed through the gastrointestinal tract. (iv) Chewable 5000ug - 27% - A dissolvabletablet of B12 that is absorbed through the sublingual mucosa (v) Liposome1000ug - 14% - A liposome oral spray of B12 with particle sizes of approximately 100 nm. The chewable showed similar increase as nano liposomal, but a 5x higher dosage was used. The standard liposomal product was 3x more bioavailable than tablet. The nano liposomal spray exhibitedsustained release with more than 5x increased bioavailability over standard tablets. Read more

Liposomal Berberine increases circulation time 23-46x

Preparation, Pharmacokinetics and Tumour-Suppressive Activity of Berberine Liposomes (Zheng, 2017) Administration of standard Liposomal Berberine  increased retention time in circulation from .42 to 10 hours. Use of PEG modified Liposomes further increased retention to to 14 hours. Administration of Berberine solution injection is hindered by unsatisfactory pharmacokinetics and, more importantly, the risk of lethal cardiovascular adverse reactions due to rapid uptake into heart and lung. This study validated common and long-circulating liposomes as safe and effective method for sustained release of Berberine. Read more

Liposomal Curcumin & Resveratrol capsules 10-20x more bioavailable in circulation and prostate tissue vs standard capsules

Liposome encapsulation of curcumin and resveratrol in combination reduces prostate incidence in PTEN knockout mice Liposome capsules of resveratrol and curcumin may inhibit prostate problems by increasing their bioavailability synergistically. In this study, we determined the bioavailability of liposome encapsulated curcumin and resveratrol, individually and in combination and evaluated the inhibitory effects of these agents against prostate  growth and progression. Serum and prostate tissue samples harvested at different time points of 30 min to12 hr with plain liposome (0.1%), curcumin (50 mg/kg/bw), lipo-curcumin (50 mg/kg/bw),lipo-resveratrol (50 mg/kg/bw) and lipo-curcumin co administered with lipo-resveratrol (25 mg/kg/bw for each) figure a - Levels of curcumin and resveratrol recorded in the serum figure b - Levels of curcumin and resveratrol recorded in the prostate figure d - Quantification of tumor growth inhibition. Total number of adenocarcinomas observed under 10 high-power fields of control vs. treatment groups. Read more