About Liposomes for Transdermal Delivery
Liposomes have emerged as an important tool for the specific and efficient delivery of various chemical and macromolecular species into the system. Liposomes were discovered in 1965 and designated as swollen phospholipid systems, specifically Banghasomes, by Alec Bangham and his colleagues, and with that paper the liposome “industry” was launched. (https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)60950-6.pdf)
They were initially used as models to study biological membranes, and as versatile delivery systems of both hydrophilic and lipophilic molecules (https://www.ncbi.nlm.nih.gov/pubmed/18217339).
What are Liposomes
A Liposome (LY-poh-SOH-m) is a nutrient formulation that contains the active nutrient inside very tiny, fat-like particles. This form is easier for the body to absorb and delivers more nutrients to target areas of the body.
Liposomes are spherical-shaped phospholipid pods filled with aqueous nutrients and indeed represent the most extensively studied and advanced drug and now supplement delivery vehicles.
After extensive research and development efforts, liposome-formulated drugs are now used routinely at clinics to treat everything from cancer to systemic or local fungal infections, mainly because they are biologically inert and biocompatible and do not cause unwanted toxic or immune reactions.
“Since liposomes are made of the same material as most cells, your body recognizes them as a friendly substance”
How are they Absorbed?
Liposomes can be designed to deliver nutrients in multiple ways. Some liposomes work to deliver nutrients by diffusion rather than by ‘direct’ cell fusion.
Other liposomes release nutrient molecules by membrane fusion with the cellular plasma membrane. The nutrient encapsulated in the liposome is protected from metabolism and the molecule becomes active only after release from the liposome sheath, and without degradation. (https://sci-hub.tw/10.1080/01635581.2018.1557212)
They are easily absorbed into the bloodstream through the skin, mucous membranes in your mouth and digestive tract. (https://www.nature.com/articles/s41598-018-31693-y)
Nutraceutical liposomes can act as both curative as well as preventive medicines and so
the nutritional industry’s use of liposomes is expected to grow rapidly in the next 5–10 years. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818067/#b13-33-36)
The transdermal route is considered a promising path for delivery of molecules into the systemic circulation. Delivery of NAD+ using this route overcomes the limitations of oral therapy and provides a steady state nutrient delivery.
Possible mechanisms of action of liposomes as skin molecule delivery systems.
- Free drug mechanism
- Penetration enhancing process of liposome components
- Vesicle absorption to and/or fusion with the stratum corneum (SC)
- Intact vesicle penetration into or into and through the intact skin (not to scale)
- Penetration of the vesicles through a hair follicle.
Adapted from EL Maghraby et al., 2008
Topical nutrient delivery across the skin can offer many advantages, such as provide sustained product release, lower oscillations in plasma drug levels, circumvent first-pass metabolism, improve user consistency, and provide local (dermal), or systemic (transdermal) effects (Schäfer-Korting et al., 2007; El Maghraby et al., 2008).
“the transdermal route overcomes the limitations of oral therapy and provides a steady state nutrient delivery”
Dermal and transdermal delivery vehicles in the form of ultra-flexible liposomes, or transferosomes, are increasingly considered the vehicle of choice, mainly because of their high performance as transdermal penetration enhancers and their good stability in suspension. (https://www.nature.com/articles/s41598-018-31693-y#article-info)
Once applied on the skin, liposomes rupture and diffuse as a lipidic mixture that acts as a penetration enhancer. Liposomal topicals and transdermals can optimize cellular uptake and effectiveness and can be easily adjusted to a lower or higher dose to meet each individual’s needs.
“Liposome delivery in lotions overcomes the limitations of oral therapy and provides a steady state nutrient delivery”
The inclusion of lipid vesicles into lotions can enhance their stability, prolong active product release, enhance transdermal permeability, and increase localization of the active within the skin (https://www.intechopen.com/books/liposomes/hydrogels-and-their-combination-with-liposomes-niosomes-or-transfersomes-for-dermal-and-transdermal-).
Absorption and Bioavailability
The advancement of liposomal formulations has led to enhanced transdermal absorption and efficacy, and research has found dermal permeability to be the highest for liposomal formulations. (https://www.sciencedirect.com/science/article/pii/S0753332218352375)
Strong barrier properties of the stratum corneum often limits the efficiency of nutrient delivery through skin. Several approaches have improved permeation of product through the skin for local as well as systemic nutrient delivery.
Incorporation of the drug within flexible liposomal vesicles, or transferosomes, has been one of the popular and well-studied approaches for delivering active product to deeper layers of the skin or even systemic circulation.
“Liposome-formulated compounds are biologically inert and biocompatible and do not cause unwanted toxic or immune reactions”
Recent research has also confirmed that small-sized liposomes greatly increase the kinetics of absorption and lengthen circulation time (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818067/).
These lipid carriers offer the capability of controlling product release, enhancing transdermal absorption and increasing bioavailability of active compounds. Carriers can also target actives to skin appendages and enhance transdermal delivery (https://www.intechopen.com/books/liposomes/hydrogels-and-their-combination-with-liposomes-niosomes-or-transfersomes-for-dermal-and-transdermal-).
Clearance is inversely related to size, with the small unilamellar liposomes and micronized emulsions circulating the blood the longest, leading to longer half-life of the biologically active substance.
“Liposomes seem to be an almost ideal drug-carrier system”
Micro-vesicle technology can act as a platform for the transdermal delivery of various micronutrients such as NAD+ through the skin using fluidizing liposomes incorporated within standard cosmetic bases (https://www.nature.com/articles/s41598-018-34205-0)
Are Transdermal Liposomes Safe
Liposomes seem to be an almost ideal drug-carrier system, since their morphology is similar to that of cellular membranes and because of their ability to incorporate various substances.
They are valued for their biological and technological advantages as optimal delivery systems for biologically active substances, both in vitro and in vivo, and are considered to be the most successful and safe substance-carrier system known to date.
“Nutraceutical liposomes could act as both curative as well as preventive medicines”
Transdermal liposomes are biologically inert and biocompatible and do not cause unwanted toxic or immune reactions (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324542/).
Additional Advantages of Transdermal Delivery of NAD+
Increasing utilization of lotions and hydrogels in transdermal delivery is largely due to their inherent properties, for example – sustained substance release for NAD+ transdermal transport, higher stability, greater percutaneous absorption, desired functionality, and nontoxic nature.
Additional advantages include ease of application, better skin compliance, skin hydration, improved product effectiveness, and convenience.
Liposomes are widely used as carriers due to the small size, both hydrophobic and hydrophilic properties, biodegradability, and high safety.
Several studies, some listed here, have demonstrated the great potential of liposomes as lipid vehicles for NAD+, which are able to enhance drug permeation through he skin and also can act as local depot for the drug to sustain and control its delivery (https://www.intechopen.com/books/liposomes/hydrogels-and-their-combination-with-liposomes-niosomes-or-transfersomes-for-dermal-and-transdermal-).