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Pharma Tech Outlook | Friday, April 28, 2023
Developing nanoparticle-based drug delivery technologies, such as lipid and polymeric nanoparticles, to achieve therapeutic concentration and minimise side effects.
FREMONT, CA: New therapies are not like the usual small or large molecules that target cell surfaces or are delivered without a specific molecular-targeting approach. Therefore, more advanced drug delivery systems release innovative molecules in tissues and cells in a targeted and controlled manner to maximise their potential advantages for patients. Researchers are dedicated to overcoming obstacles in drug development by creating various nanoparticles that can deliver new drug candidates to previously unreachable targets in tissues and cells. These nanoparticles are designed to release the drugs in formulations that are user-friendly and convenient for patients. Additionally, scientists are exploring new methods for administering biological drugs orally by finding ways to cross the intestinal wall, which has been a long-standing challenge for drug designers.
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Cell-Targeted Delivery of Therapies with Lipid Nanoparticles (LNPs)
Accessing up to 80 per cent of the targets inside cells is difficult for large-charged molecules, including nucleotide-based therapies. To overcome this challenge, there is a balanced approach of using internally developed technologies and external collaborations to develop therapies and delivery agents that can reach intracellular targets.
Research is focused on utilising lipid nanoparticles (LNPs) as a viable option for delivering nucleotide-based therapies to intracellular targets for protein production in cells. LNPs have a proven history of effectively delivering nucleic acids and are currently the most advanced method for mRNA. The ability of LNPs to deliver mRNA into cells and trigger protein production through various forms of administration, such as intravenous, subcutaneous, and pulmonary methods.
Tissue-Targeted Delivery to Expand Druggable Targets
The goal is to deliver medicine to the specific tissue requiring treatment, achieving the desired therapeutic concentration while reducing the likelihood of side effects from off-target activity at other sites.
Nanoparticles are extremely small particles with dimensions less than 100 nm. They can be utilised to transport drug candidates to their intended location, potentially enhancing the therapeutic index of traditional small molecules and new modalities. By incorporating targeting ligands and carefully selecting nanoparticles, their distribution can be altered, allowing for controlled release and an increased concentration of the drug in diseased tissue while minimising exposure to healthy tissue.
Preclinical and clinical programs involve the study of various nanoplatforms, including polymeric nanoparticles, polymer conjugates and inorganic nanoparticles. For polymeric nanoparticles, drug compounds are enclosed in a polymer matrix, whereas for polymer conjugates, they are linked chemically to branched polymers. The effective loading of these nanoparticles with drugs and regulating their release rate are critical challenges that our teams are addressing. The aim is to gain a comprehensive understanding of the effects of the combination of these particles and drugs in the body.
Ultra-small (<8 nm) silica particles, which are inorganic nanoparticles with unique biodistribution, can be attached to a drug molecule, imaging labels, and an antibody to actively target specific tissues. These particles were found to penetrate tumours and accumulate significantly in tumour tissues when linked with engineered antibody fragments for imaging and detection of HER2-overexpressing breast cancer.
The pharmaceutical industry is actively working on creating new methods for delivering drugs that can enhance the effectiveness of small molecules and new types of therapies. Through a balanced approach of internal development and external collaborations, the industries are exploring a range of nanoparticle platforms, including lipid nanoparticles, polymeric nanoparticles, polymer conjugates, and ultra-small silica particles, to deliver drug candidates to their target tissues. The foremost goal is to understand the impact of these particles and drugs on the body and achieve therapeutic concentration while minimising the potential for side effects.
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