RESEARCH ON LIPOSOMES FOR INCREASED BIOAVAILABILITY

Liposomes, vesicles enclosed by phospholipid bilayers, can solubilize water-insoluble drugs into the lipid domain of the liposomal membrane. In addition to their solubilizing capacity and biocompatibility, the structural and compositional similarity of liposomes with bio-membranes has also encouraged their application for non-invasive oral delivery of poorly-permeable nutrients. 2

Liposomes are non-toxic, biocompatible, biodegradable, and have the following advantages as carriers in drug delivery: first, liposomes can reduce toxicity; second, hydrophilic and lipophilic agents can be incorporated into liposomes; third, liposomes control the drug release; and fourth, the liposome delivery system increases bioavailability. 3

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.

Liposomal Fisetin up to 47x more Bioavailable

This study in mice found a 47-fold increase (in Cmax) with Liposomal Fisetin. The chart at left shows blood plasma levels are much higher with Liposomal Fisetin vs free Fisetin at 10x higher dosage

In vivo, liposomal fisetin allowed a 47-fold increase in relative bioavailability compared to 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 chewable tablet (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) Liposome 1000ug - 14% - A liposome oral spray of B12 with particle sizes of approximately 100 nm.

The chewable showed similar increase as nanoliposomal, but a 5x higher dosage was used.

The standard liposomal product was 3x more bioavailable than a tablet.

The nano liposomal spray exhibited sustained release with more than 5x increased bioavailability over standard tablets.

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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.

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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 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.

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Quercetin Loaded Liposomes Reduce ROS by 35%

 

New study shows liposomal quercetin offers optimal protection against oxidative stress in human intestinal cells by reducing reactive oxygen species (ROS) production.

These results highlight its capability of regulating inflammatory and oxidative conditions that can cause DNA damage.

In vitro results in human intestinal cells highlight the ability of quercetin liposomes to reduce high ROS levels, prolonging the effect of quercetin up to 6 hours inside the cell.

“The objective of this study was to develop, optimize and characterize a vesicular formulation that enhances quercetin local bioavailability, bypasses the stomach, and allows its release in the intestines for the treatment of disorders in which oxidative stress and inflammation are involved.”

Daily Liposomal Glutathione (GSH) Elevated Blood GSH Levels in Humans by 40%

Results from two recent studies showed that liposomal nanoformulation absorption is more effective for raising blood glutathione levels in humans than non-liposomal glutathione. 1

GSH levels were elevated after 1 week with maximum increases of 40% in whole blood, 25% in erythrocytes, 28% in plasma and 100% in PBMCs occurring after 2 weeks (P<0.05).

GSH increases were accompanied by reductions in oxidative stress biomarkers including decreases of 35% in plasma 8-isoprostane and 20% in oxidized:reduced GSH ratios (P<0.05).

Enhancements in immune function markers were observed with liposomal GSH administration including NK cell cytotoxicity, which was elevated by up to 400% by 2 weeks (P<0.05), and lymphocyte proliferation, which was elevated up to 60% after 2 weeks (P<0.05).

Overall, there were no differences observed between dose groups, but statistical power was limited due to the small sample size in this study.

Collectively, these preliminary findings support the effectiveness of daily liposomal GSH administration at elevating stores of GSH and impacting immune function and levels of oxidative stress.

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Enhanced Efficacy of Apigenin Liposomes

A recent study focusing on establishing apigenin as a potential chemotherapeutic agent for alleviating colorectal cancer reports the development of a stable liposomal nanocarrier with high encapsulation of the hydrophobic flavone apigenin for enhanced chemotherapeutic effects.

Research demonstrates the chemo-preventive properties of apigenin against colorectal cancer and the enhanced efficacy of its liposomal formulation both at the in vitro and in vivo level.

"Apigenin liposomes bypass the hurdles posed by apigenin as a chemotherapeutic due to its high hydrophobicity. The enhanced pharmacological activity of apigenin has been assigned to its ability to interact and subsequently influence membrane properties which also resulted in optimal yield of a stable, rigidified, non-leaky nano-carrier with ideal release kinetics."