The novel and patented technology allows controlled, enhanced, and on-demand release and delivery of active molecules (Bioactives / API).

The self-formed “complex-associated and structured liquid colloidal nano-dispersions” provide optimal delivery solutions for a variety of molecule types.

The technology is fully dilutable by almost any aqueous system and enhances the transport of active molecules to their target tissue. It can also enable higher pharmaceutical loading capacity in each dosage, with a long shelf-life due to its physical and chemical stability.

LDS formulations are solely based on safe and permitted excipients approved by the FDA and other health authorities for specific applications. These applications include oral, dermal, nasal, parenteral, and ocular routes.

LDS structures are carefully adapted and tailor-made for each active molecules (generic or innovative, small or large) and its application and required dose.

LDS uses a proprietary mathematical model (Monte Carlo Dynamic simulation) that examines and links the bioactive chemical structure and cheractertics to the excipient compositing the  delivery system, and suggests optimal alternatives to maximize the bioactive loading on the domain interface, forming a unique API-loaded drug product.

The dynamic model explores geometrical aspects, including ‘Effective Critical Packing Parameters’ (ECPP), ‘Spontaneous Curvature,’ ‘High Interfacial Elasticity,’ ‘Micro Viscosity,’ ‘Polarity,’ ‘Rheology,’ ‘Degree of Order Parameters,’ and more.

The laboratory experimental work relies on the outcomes of the model to optimize its success in designing effective delivery systems all linked and based on the platform technology.

LDS structures are composed of multiple components that self-assemble to form sophisticated and unique liquid lipid-based domains, distinct from nano-emulsions, traditional microemulsions, liposomes, and other dispersed droplets or particles.

The structured liquid domains are ‘tailor-made’ by customizing the interfacial location of each bioactive, based on its unique chemical structure, for each application and route of administration, including oral, topical, ophthalmic, parenteral, dermal, and more.

All the inactive ingredients (excipients) composing LDS’ domains are known, safe, and comply with the FDA Inactive Ingredient Guideline (IIG), as well as other regulatory guidelines for pharmaceutical, cosmeceutical and nutraceutical compositions.

The bioactive compounds are assembled at the interface (solubilized). The exact location of the API is determined and regulated. Evidence for each solubilization mode and the location of the bioactive in the liquid structure is obtained from advanced analytical tools such as PGSE-NMR (SD-NMR), Cryo-TEM, EPR, and other state-of-the-art analytical techniques.

Therefore, the interfacial solubilization capacity consistently achieves much higher loadings than the classical dissolution of bioactives in the core of classical delivery systems (e.g., emulsions). Such solubilization facilitates the delivery of the bioactive through regulated, intimate, and direct contact with the membrane.

LDS systems can solubilize significantly higher amounts of bioactive molecules while maintaining structural stability.

LDS ‘self-assembled concentrates’ (water-free/oily phase) have a very high solubilization capacity, many folds more than the dissolution quantities in traditional delivery systems. This is due to the small droplet sizes and specially designed ‘interfacial agents’ attached to the structure interface. These agents space the interface and strengthen interfacial attraction forces (e.g., interfacial elasticity and interfacial rheology) while geometrical structure builders (‘cosmotropic agents’) accommodate bioactive molecules and optimize the interface for easy ‘on-demand’ release.

The domains consist of several excipients, each having a specific role within the domains:

• Some act as ‘building blocks’ needed for the construction of the liquid droplet interface.
• Others help the system become fully dilutable.
• Some increase the loading capacity of the droplet interface.
• Others assist in adhering the domains to membrane surfaces and enhancing permeability.

The systems are composed of excipients optimized for bioavailability in the body when mixed with aqueous systems such as GI fluids.

LDS domain sizes are smaller than 100 nm, depending on their inactive ingredients (excipients), as well as the size and amount of the loaded active molecules.

The droplet sizes and contraction are determined by several 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 (with almost all domains being of the same size), both in the concentrate (water-free) and in any aqueous dilution form.

LDS products are very easy and cost-effective to manufacture and do not require sophisticated equipment. In many cases, there is no need for preservatives or antioxidants.

Yes, LDS delivery systems are a platform technology that can be designed for a range of active molecules. Each active molecule is carefully studied, both chemically and physically.

Mathematical simulations are carried out to design specific system compositions with characteristics best suited to the active molecule, while considering the required parameters and constraints of the application route and regulatory requirements (such as pH range, osmolality, viscosity, and more) .

Yes, LDS domains are designed and built to be applied as ‘liquid oily concentrates,’ soft-gels, powders, or gels and are capable of being fully dilutable in aqueous systems without any destruction of the droplets upon dilution. This is unlike many technologies where structures swell, coalesce, and disintegrate when diluted. Those common technologies do not demonstrate significant advantages beyond the solubility of the drug, and they do not exhibit significant permeation capabilities.

The unique liquid domains are assembled in an oily (lipophilic) environment, termed “assembled concatenates.”

The systems are transparent fluids, physically stable for extremely long periods of time across a wide range of temperatures (from subzero to 40℃).

Similarly, their diluted form, in any aqueous system (such as bile salts, tear film, blood, and more) remains physically stable, transparent, and Newtonian (not affected by shear).

These properties enable the formation of products with a very long shelf-life (>3 years), without phase separation, creaming, fluctuation, or other undesirable phenomena that often appear in commercial products.

In addition, the robustness of LDS systems enables their transport and storage across a range of temperatures, without the risk of damaging the product.

LDS vehicles offer high-performing solutions in various applications and fields, including pharmaceuticals, nutraceuticals, and cosmeceuticals.LDS platform delivery systems can be applied across multiple delivery routes, including oral, topical, parenteral, ophthalmic, nasal, dermal, and more.LDS systems are suitable for a variety of insoluble and soluble drug molecules.The developed formulations have already been tested in multiple pre-clinical and clinical studies, demonstrating their safety (no adverse events) and superiority over commercial products.

Yes, LDS has a line of specialized nutraceutical and cosmeceutical products designed for more efficient delivery compared to traditional methods (such as simple suspensions in oil).

Some examples of LDS products include curcumin, astaxanthin, lutein, beta-carotene, lycopene, CoQ10, omega fatty acids, cannabinoids, vitamin D3, and phospholipids such as phosphatidylserine (PS).

Oils and fats (triglycerides) must be embedded into emulsions and bonded with bile salts, and are thereafter solubilized into giant micelles before being transported to the gut membrane, where they are hydrolyzed into fatty acids and mono-glycerol esters of fatty acids.

Nanoparticles, unlike droplets loaded with drugs, can adhere irreversibly to membranes, and the body does not have a mechanism to detach, disaggregate, or dissolve them. As a result, the delivery mechanism is not clear, and the bioactives cannot be easily transported and are very difficult to remove from the body.

LDS technology mimics the human fat adsorption process, formulating structures similar to bile salt giant micelles, which can act as an alternative pathway of adsorption.

The customized LDS ‘oily nanodomains’ are constructed to load active molecules at the interface of the domains. These structures are ‘coroneted’ with excipients (‘permeating agents’), enabling improved adherence to membranes and facilitating the permeation of active molecules. Only once the domains ‘recognize’ the delivery sites will they intimately adhere to the surface, allowing the active molecule to be released and transported by passive diffusion into the bloodstream.

LDS has demonstrated in pre-clinical and human clinical studies the fast and efficient absorption of active molecules, compared to traditional commercial formulations.

LDS has developed over the years advanced analytical tools to characterize the systems.

These techniques include the study of organization on the interface, interactions at the interface, degree of order, micro-viscosity, micro-rheology, and more.

Some of these techniques include:

• Pulse Gradient Spin Echo NMR (PGSE-NMR)
• DOSY NMR
• Cryo-TEM
• Subzero Differential Scanning Calorimetry (Subzero-DSC)
• Dynamic Light Scattering (DLS)
• Electron Paramagnetic Resonance (EPR)
• Unique Raman Spectroscopy
• Environmental-SEM
• Small Angle Neutron Scattering (SANS)
• LUMiFuge

…and more.

.

With vast experience, we have successfully transferred our technology to multiple collaborators. The LDS technology is very easy to manufacture and does not require sophisticated equipment.

The products developed and transferred to our collaborators have been successfully manufactured on a very large scale, reaching hundreds and thousands of kilograms with consistent quality and efficiency.

LDS technology has been thoroughly tested in multiple pre-clinical and clinical studies. The pipeline includes several products (most under confidentiality agreements) that originated from R&D processes and are now in the late stages of clinical trials.

The developed products underwent rigorous stability studies and successfully passed with outstanding results. The technology was efficiently transferred and scaled up to produce hundreds and thousands of kilograms with ease.

Additionally, several products in the fields of cosmeceuticals and nutraceuticals are already being sold globally.

LDS holds a diverse patent portfolio with more than 40 patent applications, of which 37 are already approved in several countries around the globe. Additionally, several patent applications are currently under review.

For more information, please visit the company website.

LDS collaborators include pharmaceutical, nutraceutical, and health-driven cosmetic companies searching for effective and novel delivery carriers to:

• Increase the chemical stability of bioactives
• Solubilize insoluble active molecules
• Enhance the solubility of active molecules to higher concentrations (high loading capacity)
• Deliver bioactive molecules more efficiently (increased bioavailability)
• Address additional goals that cannot be solved by traditional delivery systems
•  

LDS has currently out-licensed its technology to both small and large national and international companies across the fields of cosmeceuticals, nutraceuticals, and pharmaceuticals. Each collaboration focuses on specific active molecule(s), indications, and routes of administration.