Nanoparticle-Based Drug Delivery Systems in CDMO R&D Programs
Maryam Daneshpour, PhD, MBA, Biotech & Pharma Market Researcher
Philipp Beck, PhD, Formulation Development Manager, Ascend Advanced Therapies
Martin Rabel, PhD, Global Sales Specialist - Biopharma Services, Cytiva
I’m Maryam Daneshpour, PhD, MBA, a Biotech and Pharma Market Researcher, and I’m pleased to be the moderator for today’s discussion on the Topic Nanoparticle-Based Drug Delivery Systems in CDMO R&D.
Nanoparticle-based drug delivery systems are redefining how therapeutics are formulated, protected, and delivered, from nucleic acid medicines to complex biologics. As drug modalities diversify, the demand for precise, scalable, and reproducible delivery technologies has surged, placing Contract Development and Manufacturing Organisations (CDMOs) at the center of innovation and translation between discovery and commercial manufacturing.
To explore this rapidly evolving landscape, we’re joined by two experts whose work spans formulation science, manufacturing strategy, and technology innovation.
1. Nanoparticle-based drug delivery has become central to biopharma innovation. In your view, what makes nanoparticles uniquely valuable for therapeutic delivery compared to other platforms?
Philipp: Nanoparticles bridge chemistry and biology. They encapsulate fragile or poorly soluble molecules, enable controlled release, and fine-tune biodistribution through their composition and size. They also form a foundation for entirely new modalities such as mRNA–LNP vaccines while improving established therapies, as seen with liposomal doxorubicin compared to conventional formulations.
Martin: Nanoparticles stand out for their ability to protect and precisely deliver fragile or insoluble therapeutics like RNA or hydrophobic molecules. They enhance potency by enabling targeted delivery to specific tissues, minimising side effects. Being fully synthetic, they’re reproducible and scalable, offering biological precision with chemical control, making them invaluable for modern therapeutics.
2. What are the biggest scientific bottlenecks today in non-viral nanoparticle systems like LNPs and liposomes, and how do they compare to the challenges faced in viral delivery systems such as AAVs or lentiviruses?
Philipp: The main bottleneck is our limited understanding of where systemic delivery truly leads us. Ethical library screening in NHPs that are euthanised for unrelated reasons, as done by James Dahlman’s group, and Jude Samulski’s detailed mapping after intravenous AAV dosing, both help reveal biodistribution, but true human predictability remains elusive.
Martin: Great question! The main hurdles for non-viral systems are biological targeting and technological/manufacturing challenges. LNPs excel in RNA delivery but struggle beyond the liver. We’re exploring ligand-based targeting and computational tools for smarter design. Manufacturing still needs tailored equipment and flexible workflows, especially for personalised therapies. Both viral and non-viral systems share challenges; precision and scalability remain key.
3. Philipp, you’ve done mRNA-LNP and AAV. What are the most non-obvious formulation differences teams only discover at scale?
Philipp: LNPs scale more predictably, while AAV production depends on the variability of cell lines. For both, freezing large bulk volumes can become a major challenge that’s hard to address early. In-use studies often reveal that formulation adjustments are needed only shortly before critical milestones such as toxicology studies.
4. Stability and shelf-life remain recurring challenges for nanoparticle formulations. Which strategies show the most promise in overcoming them?
Philipp: Many stability challenges can be mitigated by storing at –20 °C after an intentional –60 °C freezing step to ensure complete solidification. The common practice of long-term –60 °C storage often persists more from dogma than data. Combining smart freezing protocols with tailored buffers and surfactants remains the most effective approach.
Martin: Stability is indeed a critical factor for the success of LNP formulations, especially when delivering RNA-based therapeutics. Interestingly, the core stability of the LNPs themselves is quite robust, the real challenge lies in the stability of the RNA payload. RNA-LNP stability largely depends on the RNA, not the particles. Lyophilisation helps extend shelf-life, though rehydration must preserve integrity. Advances in lipid design reduce degradation, while circular and chemically modified RNAs improve durability. Together, formulation science, nanoparticle engineering, and RNA chemistry are making RNA-LNPs more stable and accessible for global therapeutic use.
5. How do you see the role of CDMOs in advancing the adoption and scaling of nanoparticle delivery systems across the industry?
Philipp: CDMOs sit at the intersection of creativity and reproducibility. They translate exploratory formulations into robust, manufacturable processes and preserve know-how across programs. Their value lies less in capacity than in continuity, where knowledge and data are converted into wisdom, the real asset if turnover rates remain low.
Martin: CDMOs enable the scalability and accessibility of LNP manufacturing, especially for smaller biotech firms lacking infrastructure. They provide flexible capacity, regulatory guidance, and technical expertise from early development to commercial production. As nanoparticle manufacturing remains unstandardized, CDMOs are evolving from service providers into innovation partners, advancing new processes, materials, and quality frameworks for emerging modalities.
6. Martin, what is the most underestimated challenge biotech companies face when approaching CDMOs for RNA-LNP projects?
Martin: A major challenge is translating lab-scale LNP formulations into GMP manufacturing. Some designs that perform well preclinically can’t scale efficiently. Early de-risking with scalable formulations saves time and cost. Another pitfall is underestimating material needs for testing and stability studies, especially in RNA-LNP projects. Open dialogue with the CDMO helps align technical, regulatory, and production strategies early.
7. How well are regulatory frameworks (FDA, EMA) keeping pace with the complexity of these advanced drug delivery systems? Where are the biggest gaps?
Philipp: Regulation still trails complexity. Fyodor Urnov highlighted this when discussing the CRISPR–LNP therapy for baby KJ. Each guide RNA is still treated as a new product, which slows innovation. His proposal for platform-based regulation, focusing on shared delivery behaviour instead of sequence-level changes, captures what the field urgently needs.
Martin: Regulators have made strong progress adapting to RNA-LNP technologies, accelerated by the pandemic. Yet definitions for key components like ionizable lipids remain unclear, and current testing frameworks often don’t fit personalised therapies. Collaboration is improving, but clearer classifications and scalable release models are needed. Early engagement with agencies helps developers navigate this evolving landscape.
8. Comparability between preclinical formulations and clinical-grade material is always a challenge. How do CDMOs build confidence in these transitions?
Philipp: Confidence comes from analytical continuity and transparent data flow across development stages. CDMOs should share their experience more actively through white papers, conference posters, and short videos. The topic may be dry, but creative communication is essential to anchor comparability thinking early in every developer’s process.
Martin: Transitioning from preclinical to GMP manufacturing often disrupts comparability. Early-stage mixing methods like microfluidics don’t always scale well. Starting with scalable processes, including representative TFF systems, reduces surprises later. CDMOs build confidence by engaging early, aligning on technology choices, and leveraging experience across programs, turning scale-up from a risk into a collaborative advantage.
9. Martin, do you see the CDMO landscape moving toward specialisation (niche nanoparticle expertise) or consolidation (large players covering everything end-to-end)?
Martin: I believe we’re seeing both dynamics play out, but at different stages of the innovative lifecycle. Early development needs specialised partners with deep nanoparticle expertise, while late-stage programs benefit from large-scale infrastructure and global reach. The most effective model combines both, a hybrid partnership where focused CDMOs innovate early and collaborate with larger organisations to ensure seamless progression from concept to market.
10. How do you see AI and machine learning influencing nanoparticle formulation and process optimisation in the near future?
Philipp: AI currently helps us work more efficiently, but true effectiveness still depends on human communication and interpretation. For formulation and process optimisation, it remains mostly smoke for now. The real challenge lies in understanding biodistribution and biological variability, which no model can yet capture or meaningfully predict.
Martin: That’s a fascinating and timely question, and also a complex one, because the AI space is evolving even faster than the nanoparticle field itself. AI’s real value lies in decoding complex, data-heavy systems. It helps identify patterns in high-throughput LNP screening and predicts structure–activity relationships for lipid components. Beyond science, it streamlines operations by automating analysis and reporting. The future isn’t AI replacing scientists but enhancing their decisions, merging data-driven insight with human intuition for faster progress.
11. Philipp, you’ve been in the field since 2015. How has the “hype vs. reality” balance shifted in nanoparticle drug delivery?
Philipp: The hype has faded, and our understanding of biodistribution remains limited. After years of chasing systemic delivery, one clear winner has emerged across nanoparticle platforms: local delivery. It offers control, predictability, and efficacy where systemic approaches still rely too much on luck and incomplete biological insight.
12. Finally, what’s the next translational breakthrough most likely to change trial success rates for advanced drug delivery systems, whether nanoparticle-based or viral?
Philipp: Real progress will come from technologies that reveal in vivo biodistribution with single-cell precision. Understanding where particles actually go, rather than assuming, will reshape formulation design and dosing. Better analytical access to living systems, not new chemistries, will likely drive the next major jump in clinical success.
Martin: There are many exciting developments on the horizon, but if I had to choose one, I’d say the next breakthrough will come from precise, personalised delivery. Reaching the right cells with minimal toxicity could transform success rates and patient outcomes. Combining targeted nanoparticles or hybrid vectors with individualised therapies, RNA, DNA, or cells, brings true precision medicine closer. Achieving this will hinge on better targeting ligands, computational tools, and adaptable manufacturing.
Author Bio
Maryam Daneshpour holds a Ph.D. in biotechnology and an MBA, combining scientific and business training. She has worked across R&D, quality control, and business development in the pharmaceutical and biotech industries, contributing to diverse projects across multiple companies with a focus on biopharmaceuticals, biosimilars, and strategic collaboration.
Philipp has 10 years of experience in nanoparticle delivery. Trained in medicinal chemistry, moved from small molecules & protein crystals to nanoparticles: started in 2015 with mRNA/LNP, moved to AAV in 2020. From crystals to capsids, always the nanoparticle nerd at heart.
Martin leads Cytiva’s BioPharma Services in EMEA, specialising in RNA-LNP technologies and CDMO solutions. With a background in Pharmacy and Nanomedicine, he supports nucleic acid therapy development and drives innovation in nanoparticle manufacturing, delivering scientific and commercial excellence across the biopharma landscape.
