Ascendia Pharmaceutical Solutions developed LipidSol® as an enabling lipid nanoparticle (LNP) technology. It can improve encapsulation and delivery of therapeutics across all modalities. Pharma and biopharma companies are using LipidSol as part of formulations in which drug molecules are entrapped in lipid structures comprised of different fatty acid compositions and headgroups.
LipidSol can adopt different shapes and sizes and can be recognized by different assemblies as shown in the figure below.1 The technology encompasses all the lipid nanoparticles to address a variety of therapeutic modalities that can’t be solubilized and delivered to diseased tissues by traditional oral, injectable, or topical routes of administration. LipidSol enables the encapsulation of drugs in the LNP by utilization of fatty acids and polar headgroup entities that are commercially available and listed in FDA inactive ingredient database (IID).
Those assemblies include:
LipidSol (liposomes) − The first generation of LNPs comprised of bilayer layers derived by spontaneous dispersion of phospholipids in water. They are good carriers of drugs encapsulated in membrane for small and large molecules.
LipidSol (solid lipid nanoparticle) are stable and comprised of solid lipids with higher drug-loading capacity and controlled release properties. They have a strong probability of releasing drugs relatively faster due to solidified lipids in the interior core.
LipidSol (nanostructured lipid carrier) are stable and comprised of liquid crystalline lipids. They have higher drug loading capacity and controlled release properties, with longer retention of drugs due to liquid crystalline drugs in the interior core.
LipidSol (immunogenic liposome) is designed with antibodies that target specific diseased tissues. They reduce the eminent toxicity to healthier cells and can be safely administered for enhanced drug efficacy.
With options to design with PEG-lated phospholipids, LipidSol (stealth liposome) can trigger longer circulation time without being taken up by RES. The result is continued delivery of molecules for an extended period, especially those applicable to controlled release and long acting injectables (LIAs).
LipidSol (lipoplex) are designed with ionizable/cationic phospholipids and can effectively protect and transport DNA and mRNA to targeted cells.
Comprised of non-lamellar structured nanocarriers, LipidSol (Cubosome) is stabilized with polymeric outer corona surface and possesses a significantly higher surface than a typical liposome. This allows for a larger area for loading small molecules and proteins.
Liposomes have been used extensively in formulation of many drug molecules.3 A handful of liposome-based drugs have been marketed commercially, as shown in Table 1.4 Because of their unique structures with inner aqueous cavity and a lipophilic bilayer interior, the drug molecules - amphiphilic and/or hydrophobic in nature - are preferentially partitioned into these assemblies. Thus, such lipid assemblies can act as effective carriers in transporting the molecules to target tissues.5
The phospholipids with varied in chain length and fatty acid compositions and headgroups, like PC, PE, PG, PS among others, spontaneously aggregate in aqueous solutions to form lipid particles ranging between 20-1000 nm. The insoluble molecules can partition into lipid interior if hydrophobic or they can partition in the aqueous interior of liposomes. These liposomes can be prepared by simple agitation to sonication to small vesicles (SUVs) with particle size ranging 20-100 nm in diameters, large unilamellar vesicles (LUVs), with particle size ranging in 100-1000 nm diameters, or multilamellar vesicles (MLVs), with particle size diameters of >500 nm.
Liposome particle size is a critical attribute for drug encapsulation and circulation half-life. Smaller liposomes circulate longer as larger sizes without being engulfed by the phagocytes.6 Several drugs approved in liposomes typically have the particle size range of 100 nm or less.7 Liposome particle size is controlled by extrusion, sonication and homogenization and is measured by dynamic light scattering, size exclusion chromatography, nuclear magnetic resonance spectroscopy and light microscopy.
Lipid headgroup plays an important role in drug delivery to the cellular level.8 The surface charges created by positive, negative and/or zwitterionic moieties contribute to potential membrane bilayers, allow partitioning and migration of drugs from outer to inner membranes and the stability of liposomes, in general. For instance, the liposomes with higher charges around the membrane and contributed by PG or PE may provide much better stability due to charge repulsions than those with neutral lipid membranes. A zeta potential -30 mV or >30 mV can lead to stronger charge repulsion and particle segregation in the suspensions than with lower zeta potential.9
Ascendia Pharmaceutical Solutions has a strong scientific team that can effectively transfer formulations they develop using LipidSol to its in-house manufacturing group. The result is an efficient and fast process to stay on schedule.
The manufacturing suite in the heart of the New Jersey Bioscience Center is state-of-the-art. It includes three NanoAssmblr (Cytiva) instrument for generation of LNPs. Ignite assembly provides “power to advance” to maximize time for generation of nanoparticles. The Blaze assembly creates the “power to scale” by serving as a direct path to nanoparticle scale up. GMP assembly creates the power to commercialize, creating a continuous flow microfluidic platform for scale up manufacturing of nanoparticles under cGMP.
Ascendia Pharmaceutical Solution’s footprint in innovative platform technology, like LipidSol, complements its expert and cGMP manufacturing capabilities to tackle the challenges in injectable formulations requiring controlled delivery of small molecules, biologics and genes.
Contact us today to learn more about how we can be your Fast, Flexible, and First Time Right CDMO partner.
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