Questions and Answers

Many delivery technologies have been explored and developed for active molecules (API, bioactive and others) for the health industry.
Most delivery technologies are based on solid particles (such as powders, capsules and spheres), or on liquid formulations (such as emulsions, mini-emulsions, microemulsion, nanoemulsions) and other delivery technologies (including Liposomes, Ethosomes, Cubosomes, Hexosomes).
LDS offers a novel approach based on molecular architectures, designed and engineered using unique computer mathematical simulation programs, taking into consideration the interfacial phenomena, optimum surface area, the release pattern of the active molecule, as well as additional parameters, in order to compose LDS’ liquid structures.
LDS systems are self-formed “complex associated colloids” that provide ‘delivery solutions’ for enhanced performance of various bioactive molecules for different applications such as oral, dermal, nasal, parenteral, ocular and more.

The LDS model considers compositions based on geometrical aspects (‘Effective Critical Packing Parameters’ (ECPP), ‘Spontaneous Curvature’, ‘High Interfacial Elasticity’, ‘Micro Viscosity’, ‘Polarity’, ‘Rheology’, ‘Degree of Order Parameters’ and more) in the design of the delivery systems.
LDS structures are composed of multiple components that self-assemble to form liquid lipid-based domains, different from nanoemulsions, traditional microemulsions, liposomes and/or other dispersed droplets or particles.
The domains are ‘tailor-made’ by customizing the structure and the location of each bioactive for each application and route of administration (oral, topical, ophthalmic, parenteral, dermal and more).
The structures are sophisticate domains (“Bonbons like”) vehicles solubilizing the active compound at their interface. LDS’ structures can solubilize insoluble active molecules with relatively high loading capacity.

All the inactive ingredients composing LDS’ domains are known, safe, regulated based on the FDA IIG list for pharmaceutical requirements, and comply with the regulatory guidelines. LDS liquid structures meet also the health requirements for cosmeceutical and nutraceutical compositions.

The bioactive compounds are assembled in the novel domains and are solubilized at the interface (evidence from advanced analytical tools such SD-NMR), and not in the core of the structures.
Therefore, the solubilization capacity is always much higher than the dissolution of the bioactive in the classical delivery vehicles (for example in emulsions). LDS systems can solubilize relatively high contents of bioactive molecules while still keeping the structure stable.

LDS ‘assembled concentrates’ (water-free / oily phase) have very high solubilization capacity, many folds more than the dissolution quantities in traditional delivery systems, because of the existence of ‘interfacial molecules’ attached to the structure interface by spacing it, and the geometrical structure accommodating the bioactive molecules.
The nanodomains consist of several excipients each of them has a specific role in the domains. Some are ‘building blocks’ needed for the construction of the interface of the liquid droplets, while others are helping the system to be fully dilutable, others are assisting to increase the loading capacity of the droplets interface, and others assist to adhere the domains to the membrane surface, and to permeate it.
The systems are composed of excipients for optimal bioavailability in the body when mixed with aqueous system such as the GI-fluids”.

LDS domains size is smaller than 100nms, depending on their inactive ingredients (excipients), size and amount of the loaded active molecules. The droplets sizes and contraction are determined by several very advanced analytical tools such as SAXS, EPR, PGSE-NMR, Cryo-TEM and DLS.

Formulations are self-assembled, prepared without applying shear or temperature and are almost mono-dispersed (almost all the domains are of the same size) in the concentrate (water-free) and in any aqueous dilution form. Therefore, LDS products are  very easy to manufacture and do not require any sophisticated equipment.

Yes, LDS delivery systems are a platform technology that can be designed for a range of active molecules and bioactives. Each active molecule is chemically and physically carefully studied. Mathematical simulations are carried-out to design specific systems compositions with characteristics to best suit the active molecule, while taking into consideration the required parameters and constrains (such as pH range, osmolality, viscosity and more).

Yes, LDS domains are designed and built to be applied as ‘liquid oily concentrates’, softgels, powders, or gels and are capable of being fully dilutable in aqueous systems without any destruction of the droplets upon dilution (unlike some structures that disintegrate when diluted and lose their permeation capabilities).

The unique domains are assembled in an oily-phases that are termed “assembled concatenates”, or “Bonbons”. The systems external appearance is of transparent fluid, physically stable for extremely long periods of time in wide range of temperatures (from subzero to 40℃). Similarly, their diluted form, in any aqueous systems (such as bile salts, tear film, blood and more) remains physically stable, transparent, and Newtonian (not affected by shear). This enables formation of products with a very long shelf-life (>2 years), without phase separation, creaming, fluctuation and other phenomena that appear in commercial products. In addition, the robustness of LDS’ systems enable their transport and storage, at a range of temperatures, without the risk of damaging the product.

The nanodomains are stable and not affected from pH fluctuations, and are resistant also to considerable high levels of electrolytes.

LDS vehicles offer high performing vehicles in various files, including pharmaceuticals, nutraceuticals and cosmeceuticals. LDS platform delivery systems can be applied in a number of delivery routes including oral, topical, parenteral, ophthalmic, nasal, dermal and more. LDS systems are suitable for various insoluble and soluble drug molecules.

Yes, LDS has a line of specific nutraceutical and cosmetoceutical product for a more efficient way of delivery than in traditional types of delivery (such as simple suspensions in oil). Some examples include: curcumin, astaxanthin, lutein, beta carotene, lycopene, CoQ10, omega fatty acids, cannabinoids, phospholipids,  such as phosphatidyl serine (PS) etc.

LDS had developed delivery vehicles to help permeate drugs across the eye epithelium to deliver insoluble molecules, as well as biopolymers, to the front and the back of the eye. In pre-clinical studies we showed that LDS’ delivery system its superiority by demonstrating that the active molecule had reached the target tissue in a much higher concentration compared to the commercial product with the same dose.

It is known that fatty acid, and glycerol esters of fatty acids are transported across the gut’s membranes with or without the help of a transporter.
However oils and fats (triglycerides) must be embedded into emulsions bond on bille salts and thereafter are solubilized into giant micelles prior of being transported to the guts membrane where they are hydrolyzed into fatty acids and mono glycerol esters of fatty acids.
Nanoparticles, unlike droplets, loaded with drugs, do not have a mechanism in the body, and the body does not have a mechanism to disaggregate, or dissolve them, and therefore, cannot be easily ‘transported’.
LDS technology is mimicking the human fats adsorption process i.e., formulation of structures similar to bile- salts giant micelles that can act as an alternative pathway of adsorption.
LDS is designing domains with characteristics similar to the ‘bile salts giant micelles’ but with high bioactive loading capacity and strong affinity to the GI membrane.
The customized LDS’ ‘oily nanodomains’ are constructed, so that the active molecules will be loaded at the interface of the domains. The structures are ‘coroneted’ with excipients (‘permeating agents’) enabling improved adherence to membranes and facilitates the permeation of the active molecules.
Only once the domains “recognize” the delivery sites, will they adhere to the surface and allow the active molecule to be released and transported by passive diffusion to the blood stream. LDS’ had showed in pre-clinical studies, as well as in human clinical studies, the fast and efficient absorption of the active molecule compared to traditional commercial formulation.

LDS developed advanced analytical tools to characterize the nanodomains. Some of these techniques include organization on the interface, interactions at the interface, degree of order, micro viscosity and more. Some of these techniques include, Pulse Gradient Spin Eco NMR (PGSE NMR), DOSY NMR, Cryo-TEM, Subzero Differential Scanting Calorimetry (Subzero-DSC), Dynamic Light Scattering (DLS), Electron Paramagnetic Resonance (EPR), Unique Raman Spectroscopy, Environmental-SEM, Small Angle Neutron scattering (SANS), LUMiFuge and more.

LDS collaborators are pharmaceutical, nutraceuticals and cosmetic companies, searching for effective and novel delivery carriers to increase chemical stability of the bioactive, to solubilize the active molecule in higher contents (high loading capacity) and to deliver the bioactive molecules in a more efficient way (increase bioavailability).

LDS has a diverse patent portfolio composed of more than 9 patent application families, some of which are already approved, in several countries around the globe, and some are pending patent-applications under review. For additional information please search the company website.