Soft- and hard-lipid nanoparticles: a novel approach to lymphatic drug delivery

Abstract

With the current advance in nanotechnology, the development has accelerated of a number of nanoparticle-type drugs such as nano-emulsions, lipid emulsions, liposomes, and cell therapeutics. With these developments, attempts are being made to apply these new drugs to healing many intractable diseases related to antibody production, autoimmune disorders, cancer, and organ transplantation in both clinical and nonclinical trials. Drug delivery to the lymphatic system is indispensable for treating these diseases, but the core technologies related to the in vivo distribution characteristics and lymphatic delivery evaluation of these particle-type drugs have not yet been established. Additionally, the core technologies for setting up the pharmacotherapeutic aspects such as their usage and dosages in the development of new drugs do not meet the needs of the market. Therefore, it is necessary to consider dividing these particle-type drugs into soft-lipid nanoparticles that can change size in the process of body distribution and hard-lipid nanoparticles whose surfaces are hardened and whose sizes do not easily change in vivo; these soft- and hard-lipid nanoparticles likely possess different biodistribution characteristics including delivery to the lymphatic system. In this review, we summarize the different types, advantages, limitations, possible remedies, and body distribution characteristics of soft- and hard-lipid nanoparticles based on their administration routes. We also emphasize that it will be necessary to fully understand the differences in distribution between these soft- and hard-lipid nanoparticle-type drugs and to establish pharmacokinetic models for their more ideal lymphatic delivery.

Enhanced Lymphatic Delivery of Methotrexate Using W/O/W Nanoemulsion: In Vitro Characterization and Pharmacokinetic Study

“…That study’s findings are further strong evidence that the lymphatic system is a major pathway for cancer metastasis. These findings also suggest that studies on lymphatic targeting and migration of anticancer drugs are crucial, and, in fact, researchers have studied a number of targeting strategies and benefits based on the structural and physiological characteristics of the lymphatic system related to drug delivery [ 6 , 7 , 8 , 9 ]. Researchers have also reported on improving bioavailability and efficacy through formulations of conventional drugs [ 10 , 11 , 12 , 13 ].…”

“…Formulations using polymers have mechanical stability because of a hardened surface and a solid core, but their structural rigidity makes these formulations less flexible, which may limit penetration into the vascular wall [ 8 , 26 ]. In addition, these hard particles may trigger more phagocytosis by phagocytic elements, and they may cause pain or allergic reactions when administered [ 27 ].…”

“…In addition, these hard particles may trigger more phagocytosis by phagocytic elements, and they may cause pain or allergic reactions when administered [ 27 ]. In contrast, formulations with a fluid surface, including emulsions, flow more easily through the blood vessels and into the lymph nodes [ 8 ]. Nano-sized emulsions are at a sufficiently small scale to penetrate into the lymph, and they have a larger surface area that provides greater absorption [ 28 ].…”

Preparation and In Vitro/In Vivo Characterization of Polymeric Nanoparticles Containing Methotrexate to Improve Lymphatic Delivery

“…The delivery of MTX to lymphatic system is closely related to the immune system. Nano-sized drugs can be transferred to the lymphatic system through diffusion into the intercellular space of porous lymphatic walls [29,30,31]. Improved target delivery of MTX with nanoscale drug carriers can reduce the dose of MTX needed for the patient and maximize its therapeutic effect, thus reducing side effects.…”

Incorporation of Antibiotics into Solid Lipid Nanoparticles: A Promising Approach to Reduce Antibiotic Resistance Emergence

“…For instance, in systemic administration, it seems that 50–200 nm-sized nanoparticles are optimal to obtain a long circulatory condition, but this range can vary depending on nanoparticle composition and shape [ 41 , 43 , 44 ]. Moreover, SLNs larger than 500 nm present reduced access to de lymphatic system [ 45 ] and nanoparticle size also seems relevant to treat central nervous system infections, as only SLNs smaller than 200 nm seem to efficiently overpass the blood–brain barrier [ 41 , 44 ]. Additionally, to treat intracellular infections, it must be taken in mind that nanoparticle size can influence nanoparticle uptake mechanism by infected eukaryotic cells, and the internalization pathway can be relevant for the improvement of drug efficiency [ 46 , 47 ].…”