Nanomaterial Platforms for API Delivery

Despite the challenges associated with bringing new nanotherapeutics to market, many companies are in active Phase I and Phase II trials with nanoparticle-based drugs. The role of lipid nanoparticles, particularly as mRNA delivery vehicles for combating COVID-19, had a tremendous global impact on the use of nanoparticle therapeutics. As of 2021, over 30 nanoparticles have been used in clinical applications, 20 of which are still in development with increasing activity in clinical trials. Of the 60 unapproved nanoparticle technologies (including silica, gold, iron, polymer, and lipid-based nanoparticles) being investigated in clinical trials, over 100 active trials exist.¹

Liposomal/Lipid Nanoparticles

Liposomal and lipid nanoparticles (LNPs) are among the most extensively studied and regulatory-approved nanocarriers, with established applications in vaccines, cancer therapeutics, and gene transfection. These highly biocompatible systems exhibit excellent encapsulation efficiency for a range of payloads, including messenger RNA (mRNA), small hydrophilic molecules, and hydrophobic drugs.² Encapsulation within lipid bilayers offers protection and stabilization of sensitive cargo during systemic circulation, helping to preserve the cargo until it reaches its destination. While surface modification of LNPs is comparatively limited, functional tuning is typically achieved by incorporating lipids with varying charge characteristics to tune targeting efficiency and circulation profiles. Additionally, the surfaces of alternative nanomaterials can be coated with lipids to improve biocompatibility and enhance circulation time. Lipid nanoparticle uptake mechanisms include endocytosis, passive and active targeting, and membrane fusion. However, compared to other nanocarrier platforms, LNPs are relatively prone to degradation and may exhibit burst release behavior. Despite these limitations, several lipid nanoparticle formulations—encapsulating chemotherapeutic agents and mRNA—have received approval from the FDA and EMA.³

Polymeric Nanoparticles

Over the last few decades, polymeric particles, specifically polylactic acid (PLA) and poly (D,L-lactide-co-glycolic) acid (PLGA) particles, have been a popular choice for drug delivery due to their FDA and EMA approval for therapeutic uses, biocompatibility, and biodegradability.⁴ These particles can be fine-tuned to specific diameters, and the material properties can be adjusted to allow for the control of degradation and release rate of encapsulated materials. Additionally, PLGA nanoparticles can be modified at the molecular level to target specific tissues. The polymeric terminal ends can be customized for a great deal of versatility in surface functionalization and the attachment of ligands, antigens and antibodies for targeted applications. Compounds and APIs such as hydrophobic or hydrophilic small molecules, peptides, proteins, and genetic material (e.g. RNA) can be loaded or encapsulated inside the particles, protecting them from degradation before being released at a desired rate and location.

Silica Nanoparticles

Solid silica (amorphous SiO₂) nanoparticles can be reproducibly fabricated to specific diameters, have easily modified surfaces, and are biocompatible. Due to these factors, silica is a popular choice for the delivery of a wide range of APIs. The nanopores of solid silica nanoparticles allow for the incorporation of low molecular weight species. Alternatively, the surface can be made highly positive, which allows for the adsorption and delivery of genetic materials, such as silencing RNA (siRNA), to specific cells.

Mesoporous silica nanoparticles (MSN) are a material of choice for targeted delivery of APIs for cancer therapy and other treatments due to their large surface area, large pores, versatile surface modification, and biocompatibility.⁵ By varying pore size, pore morphology, and surface chemistry, a variety of APIs can be accommodated with a large increase in encapsulation efficiency when compared to conventional nanoparticle drug carriers such as lipid-based and polymeric nanoparticles. The surface functionalization allows for the potential targeting of specific tissues or cells, or to increase the retention rate and circulation time. Although mesoporous silica is generally stable, MSN can also be designed to be degradable to facilitate controlled release of its contents.⁶ The pore sizes and structures can be tailored to include loading of smaller drugs such as doxorubicin, ibuprofen, and cisplatin or small genetic material and proteins such as siRNA and albumin. For larger APIs such as antibodies, mRNA/plasmid DNA, and CRISPR/CAS9, MSN can be synthesized with extra-large pores. The loading capability of MSN is up to 30% by weight for small molecules and 10% by weight for mRNA in large pore MSN, enabling enhanced delivery.

Gold Nanoparticles

Gold nanoparticles are chemically inert, biocompatible, and most notably have unique optical properties that can be tuned from visible to near infrared (NIR) wavelengths by changing the particle size or shape. Because of these characteristics, gold nanoparticles are the most widely used metal for nanoparticle drug delivery and therapeutic applications. Gold nanoparticles can be synthesized in a variety of morphologies including spherical, nanorods, and nanoshells to target specific wavelengths of light for photoinduced drug release or photothermal effects. Additionally, gold nanoparticles can be fabricated at ultrasmall sizes at which they are able to penetrate nuclear envelopes and deliver genetic material. The surface of gold nanoparticles can be functionalized with several different ligands that allow for the binding of compounds and APIs such as doxorubicin, hyaluronic acid, folate, polymers (polyethylene glycol, poly(N-isopropylacrylamide)), proteins (ovalbumin, biotin, antibodies), DNA and RNA (siRNA and shRNA) to aid in targeting and drug delivery. Once the gold nanoparticles have reached the target location, their payload can be released through irradiation by NIR light and plasmonic heat generation.^7–12

Iron Oxide Nanoparticles

Iron oxide nanoparticles (IONPs) have emerged as promising candidates for a range of nanomedicine applications due to their inherent biocompatibility, relatively low toxicity, and distinctive magnetic properties. These features make them particularly well-suited for targeted drug delivery systems. IONPs can be synthesized with precise control over diameter, morphology, and surface chemistry. This allows for the conjugation of APIs and targeting ligands, including nucleic acids (e.g., siRNA, plasmid DNA), chemotherapeutic agents, polymers, peptides, and antibodies. Targeted delivery can be achieved through passive accumulation, active targeting, or with the guidance of an externally applied magnetic field.¹³ Ultrasmall IONPs can be engineered to penetrate nuclear membranes, expanding their potential for intracellular and nuclear delivery. Furthermore, iron oxide can serve as a superparamagnetic core in gold nanoshell composites, offering a multifunctional platform that integrates magnetic responsiveness with the optical properties of gold.

Advancing Nanomedicine Technologies at nanoComposix

Nanomedicine development and manufacturing can pose significant challenges, including attaining consistent particle size and quality, customizing physical and bio-functional properties, scaling up production while maintaining quality, and traversing the intricacies of regulatory requirements such as cGMP compliance. These formulations are technically demanding, requiring optimization to ensure effective targeting and controlled release. Nanoparticle formulation is our key focus, setting us apart from traditional formulation development service providers.

At nanoComposix, our contract development and manufacturing services are rooted in deep expertise in nanoparticle fabrication, characterization, and development. We specialize in developing tailored nanoparticle formulations for the delivery of your active pharmaceutical ingredient (API). We offer personalized support throughout your project, ensuring consistent nanoparticle reproducibility, confirmation of particle specifications, and successful scale-up for commercialization. Our comprehensive CDMO services expedite the commercialization of your nanomedicine innovations while minimizing risk.

References

1. Anselmo AC, Mitragotri S. Nanoparticles in the clinic: An update post COVID-19 vaccines. Bioeng Transl Med. 2021;6(1):e10246. doi:10.1002/btm2.10246
2. Tenchov R, Bird R, Curtze AE, Zhou Q. Lipid nanoparticles: From liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano. 2021;15(11):16982-17015. doi:10.1021/acsnano.1c04996
3. Hou X, Zaks T, Langer R, Dong Y. Lipid nanoparticles for mRNA delivery. Nat Rev Mater. 2021;6:1078-1094. doi:10.1038/s41578-021-00358-0
4. Danhier F, Ansorena E, Silva JM, et al. PLGA-based nanoparticles: An overview of biomedical applications. J Control Release. 2012;161(2):505-522. doi:10.1016/j.jconrel.2012.01.043
5. Li Z, Barnes JC, Bosoy A, Stoddart JF, Zink JI. Mesoporous silica nanoparticles in biomedical applications. Chem Soc Rev. 2012;41(7):2590-2605. doi:10.1039/C1CS15246G
6. Hao X, Hu X, Zhang C, et al. Hybrid mesoporous silica-based drug carrier nanostructures with improved degradability by hydroxyapatite. ACS Nano. 2015;9(10):9614-9625. doi:10.1021/nn507485j
7. Tao Y, Lin Y, Wang H, Liu S. Light: A magical tool for controlled drug delivery. Adv Funct Mater. 2020;30(49):2005029. doi:10.1002/adfm.202005029
8. Moorcroft SC, Roach LG, Jayne DG, Ong ZY, Evans SD. Nanoparticle-loaded hydrogel for the light-activated release and photothermal enhancement of antimicrobial peptides. ACS Appl Mater Interfaces. 2020;12(22):24544-24554. doi:10.1021/acsami.9b22587
9. Vines JB, Yoon JH, Ryu NE, Lim DJ, Park H. Gold nanoparticles for photothermal cancer therapy. Front Chem. 2019;7:167. doi:10.3389/fchem.2019.00167
10. Gao Q, Chen C, Cheng J, Guo X. Gold nanoparticles in cancer theranostics. Front Bioeng Biotechnol. 2021;9:647905. doi:10.3389/fbioe.2021.647905
11. Kennedy LC, Bickford LR, Lewinski NA, et al. A new era for cancer treatment: Gold‐nanoparticle‐mediated thermal therapies. Small. 2010;7(2):169-183. doi:10.1002/smll.201000134
12. Liu J, Liang H, Li M, et al. Gold nanorods coated with mesoporous silica shell as drug delivery system for remote near infrared light‐activated release and potential phototherapy. Small. 2015;11(19):2323-2332. doi:10.1002/smll.201402145
13. Alphandéry E. Iron oxide nanoparticles for therapeutic applications. Drug Discov Today. 2020;25(1):141-149. doi:10.1016/j.drudis.2019.09.020