Nanoparticles: Revolutionizing Drug Delivery

Drug delivery entails administering a drug molecule to the desired location. The objective is to minimize side effects while improving therapeutic efficacy. Nanoparticles have proven to be promising drug delivery platform, and a lot of research is being done focused on leveraging them for benefits such as targeted delivery, sustained/modified release, delivery to hard-to-access physiological systems (blood-brain-barrier), etc.

Scope
Nanotherapeutics represent the latest leap in medicine, with nanotechnology being widely adopted across the board courtesy of an ever-growing body of evidence for remarkably improved drug delivery, drug release, and therapeutic efficacy. A newly developed drug and its process of delivery into the body hold equal value in the success of a treatment. Drugs with excellent pharmacokinetic profiles can show high efficacy only when targeted at the diseased region of the organ without interacting with other parts of the body. They should be able to easily cross the cell membrane, and only target the affected tissue. This would not just decrease the dosage, but also ensure fewer side effects — the process is known as active targeting. Drugs that actively target typically consist of surface modified nanoparticles functionalized by attaching ligands, such as antibodies and proteins, to enhance their uptake by the targeted site.

Lipid-based particles, such as liposomes, and other materials, for instance, polymers, metallic nanoparticles, carbon/titanium nanotubes, peptide-based nanostructures, and quantum dots, are some examples of nanoparticles that have been tested as potential drug delivery systems. Specific drug delivery vehicles are being developed to treat a wide range of diseases such as cancer, pulmonary tuberculosis, diabetes, Parkinson’s, and Alzheimer’s. These are particles that typically vary between 1nm to 100nm in size, and drugs can either be attached to the particle surface or encapsulated in the nanoparticle. Nanoparticle-based drug formulations are activated, once they reach the target site, by a specific physiological condition unique to the target site, for instance, pH, temperature, and osmolality. Apart from small molecule therapeutics, biomolecules such as peptides, nucleic acids (DNA and RNA), and genes can also be conjugated to the nanoparticles for improving treatment of chronic diseases.

Market ecosystem
Various nanodrugs have been developed and successfully commercialized. As per Pharmacy and Therapeutics 2017, around 50 nanopharmaceutical products have been approved by FDA since 1995. Doxil (doxorubicin hydrochloride, developed by Janssen Pharmaceuticals) was the first nanoformulation that received the FDA’s approval for the treatment of Kaposi’s sarcoma in people with human immunodeficiency virus (HIV). A few nanoformulated biopharmaceuticals have also been approved by the FDA. For instance, in August 2018, Alnylam Pharmaceuticals, Inc. received the FDA’s approval for its RNAi therapy‐delivering nanoparticle, Patisiran/ONPATTRO, to treat polyneuropathy.

Numerous players have developed nanoparticle-based platform technologies. Canada-based Precision NanoSystems, Inc. developed NanoAssemblr™, a cartridge-based microfluidic mixing system used for the development of a variety of nanoparticles to deliver therapeutics. StaniPharm, a contract development and manufacturing organization (CDMO), has developed StaniTab®, a unique supercritical fluid technology platform to produce dry powders comprising nanoparticles.

Cristal Therapeutics has developed CriPec^®, a nanotechnology platform which enables the design of nanomedicines with high efficacy. To achieve this, tuneable polymers with biodegradable drug linkers are combined with the therapeutic. A nanotechnology platform offered by Advanced NanoTherapies, Inc. leverages patented biodegradable functionalized nanoparticles (f-NPs); the company also has its own coating process, created at its Cleveland clinic, to enhance drug uptake and retention into a cell.

Many nanoparticle-based drug delivery systems comprising lipid- and polymer-based nanocarriers have been developed and marketed to treat oncological diseases. UK-based N4 Pharma offers Nuvec^®, a non-viral adjuvant delivery system for the development of vaccines and cancer treatments. It has an irregular (spiky) surface with polyethyleneimine (PEI) that encloses and safeguards nucleic acids (such as mRNA/pDNA) while the nucleic acid travels to the target site.

Astrazeneca, a major pharma player, is working on next-generation drug delivery technologies. Its team is working on developing a broad range of nanoparticles that can deliver new therapeutics to previously undruggable targets and control their release in easy-to-use formulations. Astrazeneca is also exploring new ways to transport oral formulations of biologic drugs through the intestinal wall, and assessing lipid nanoparticles (LNPs) as a medium for intracellular delivery of mRNA to produce protein therapeutics in cells.

Several universities are actively engaged in developing nanoparticle-based drug delivery systems. Researchers at Massachusetts Institute of Technology presented a theory that nanostructures coated with the right-handed form of cysteine (D- cysteine) can avoid its destruction by enzymes present in the body, and hence, ensure a more effective drug delivery. Wyss Institute has developed NanoRx, a novel drug targeting nanotechnology, which helps accumulate drugs at the sites of vascular occlusions; it can also be targeted with the help of ultrasound.

Hospitals and research centers are exploring this field to help improve treatment. Researchers at Brigham and Women's Hospital and Boston Children's Hospital collaborated to develop a nanoparticle platform for the effective delivery of therapeutic agents to the brain. The team demonstrated that siRNA-loaded nanoparticles led to three-fold higher accumulation of the agent in mice brain compared to the conventional delivery system.

Partnerships
The domain is witnessing active collaborations and partnerships. Dolomite Microfluidics, a developer of innovative microfluidic products, and Phosphorex, a CDMO specializing in sustained release formulation, nanomedicine, and nucleic acid delivery, partnered to develop nanoparticle formulations to treat different indications.

GenEdit, Inc., a developer of novel non-viral, non-lipid nanoparticle technology platform, and Editas Medicine, Inc. successfully collaborated for nanoparticle-based gene delivery. Acuitas Therapeutics, which is currently investigating delivery systems for nucleic acid therapeutics based on LNPs, collaborated with CureVac to develop LNP-formulated mRNA product candidates.

Nanotechnology has also proven to be a promising approach for vaccine production, especially for treating COVID-19. Merck and BioNTech extended their partnership to speed up the supply of lipids used in the production of Pfizer-BioNTech COVID-19 vaccine (BNT162b2). CanSino Biologics and Precision NanoSystems joined forces to develop an mRNA-LNP vaccine against COVID-19.

Outlook
Despite the several benefits of nanotherapeutics, only a few related innovations have been approved owing to the challenges at different stages of development. A key concern is nanotoxicity, which results from the accumulation of nanoparticles at the target site. According to Characterization and Biology of Nanomaterials for Drug Delivery, the utilization of nanomaterials, such as nanopolymers and metallic nanoparticles, has been reported to result in site-specific toxicity, blood/tissue-related toxicity, and nephrotoxicity.

These challenges can be overcome by:

• Introducing specific regulatory protocols to characterize and standardize nanotherapeutics
• Using natural and plant-based polymers, such as chitosan, to improve the safety profile of nanomedicines

Given the capability of nanoparticle-based drug delivery systems for improving treatment, the domain is attracting researchers across segments indicating bright prospects going forward.