Lipid-based delivery strategies are transforming how modern drugs, biologics, and nucleic acids are formulated, making it easier for difficult molecules to stay stable, dissolve efficiently, and reach their intended targets. Because lipid carriers mimic natural cell membranes, they improve absorption and protect sensitive compounds in ways traditional systems cannot. As researchers continue to explore liposomes, LNPs, SLNs, NLCs, and other innovative lipid platforms, these technologies are rapidly becoming essential tools across pharmaceutical and biotechnology development. For teams looking to advance next-generation delivery systems, understanding how lipid-based delivery strategies work is now more important than ever— and Creative Biolabs is here to partner with you every step of the way.

What Are Lipid-Based Delivery Systems?

Lipid-based nanocarriers are nano-sized delivery systems built mainly from lipids, such as phospholipids, triglycerides, and fatty acids. These tiny particles usually range from a few tens to a few hundred nanometers in diameter. They are designed to encapsulate, protect, and deliver a wide range of molecules, including small molecules, peptides, proteins, RNA, DNA, and hydrophobic bioactives (e.g., nutraceuticals, cosmetic actives). Because lipids are similar to the components of biological membranes, these nanocarriers are generally biocompatible and well-tolerated, which makes them highly attractive in modern formulation science.

How Lipid-Based Delivery Strategies Work

Most lipid-based delivery systems work by addressing key drug delivery challenges through lipids' unique biological compatibility, with clear, science-backed mechanisms.

Encapsulating the active compound

The drug, nucleic acid (like DNA/siRNA), or bioactive is trapped in tailored lipid structures, such as liposomes (lipid shells), solid lipid nanoparticles (SLNs, solid lipid matrices), or emulsion droplets. This step locks the cargo in a stable form, preventing aggregation and ensuring consistent dosing, critical for formulations like oral lipid capsules or injectable LNPs.

Protecting the cargo

The lipid environment shields sensitive molecules from enzymes, pH, and oxidation. For example, lipid nanoparticles safeguard mRNA from degradation before it reaches target cells, preserving potency.

Helping the cargo dissolve

Over 40% of new drugs are poorly water-soluble, limiting absorption. Lipid systems (with surfactants/cosolvents) keep these drugs dissolved or dispersed, ensuring their availability for uptake. A good example is the oral application of self-microemulsifying systems (SMEDDS), which keep the drug dissolved in the formulation. When administered orally, SMEDDS rapidly forms fine emulsions in gastric fluid, maintaining the drug's dissolution and significantly enhancing its absorption efficiency.

Interacting with biological membranes

Since cell membranes are lipid bilayers, lipid carriers can merge, fuse, or be taken up more easily. Cationic lipid carriers (e.g., CNLCs) can even adhere to negatively charged cells via electrostatic attraction, thereby enhancing retention.

Bypassing first-pass effects in some cases

Oral drugs often get broken down by the liver (first-pass metabolism). Lipid systems such as SEDDS can trigger lymphatic transport, enabling drugs to travel via lymph (not the liver's portal vein), thereby cutting metabolism and boosting bioavailability for therapeutic agents.

In short, lipid-based strategies wrap "difficult" molecules in a biology-mimicking environment, solving solubility, stability, and absorption issues and making them a go-to for formulators.

A Tour of Lipid-Based Delivery Systems

To fully grasp lipid-based drug delivery, it is essential to understand its structural diversity. As visualized in the figure, these systems fall into three core categories: Emulsion, Vesicular system, and Lipid particulate system—each with sub-types tailored to specific delivery challenges such as solubility, stability, and tissue targeting. Let's explore each category in depth, introducing the main lipid carriers.

Fig.1 Classification of lipid-based drug delivery systems.³

1. Emulsion Category

Emulsions are dispersions of oil and water, stabilized by surfactants or particles.

Nanoemulsions

Nanoemulsions are very fine oil-in-water or water-in-oil emulsions, stabilized by surfactants.

• They have droplet sizes typically below 200 nm.
• They increase the solubility and absorption of poorly soluble drugs.
• They show good kinetic stability and a clear or translucent appearance.

Nanoemulsions support oral, dermal, parenteral, and even ocular delivery strategies.

Self-Emulsifying Drug Delivery Systems (SEDDS)

SEDDS are mixtures of oil, surfactant, and cosolvent that spontaneously form emulsions in GI fluids.

Once in the stomach or intestine, they form fine emulsions or microemulsions.

They keep the drug in solution during digestion.

This process can significantly boost oral bioavailability.

SEDDS are one of the most practical lipid-based delivery strategies for oral drugs with low water solubility.

Pickering Emulsions

Pickering emulsions are stabilized not by surfactants, but by solid particles at the oil-water interface.

These particles can be modified lipids or other biocompatible materials.

They offer excellent physical stability. They are attractive for food, cosmetic, and pharmaceutical applications.

Pickering emulsions add another dimension to lipid-based delivery strategies where "clean label" and stability are important.

2. Vesicular System Category

Vesicular systems are vesicle-shaped (spherical) structures with a lipid bilayer, enclosing an aqueous core. They are incredibly versatile.

Liposomes

Liposomes are spherical vesicles with one or more lipid bilayers surrounding an aqueous core.

• They can carry hydrophilic drugs in the core and lipophilic drugs in the bilayer.
• Their composition often mimics cell membranes, which improves compatibility.
• Liposomes are widely used in oncology research, vaccines, and imaging agents.

Because they are so flexible, liposomes remain one of the most studied lipid-based delivery strategies.

Ethosomes

Ethosomes are soft vesicles made of phospholipids and high concentrations of ethanol.

• Ethanol fluidizes skin lipids and increases permeability.
• Ethosomes can carry both hydrophilic and lipophilic molecules into deeper skin layers.
• They are popular in transdermal and dermal delivery research.

Ethosomes are a good choice for lipid-based delivery strategies focused on skin penetration.

Transfersomes

Transfersomes are ultra-deformable vesicles with special surfactants called edge activators.

• They can squeeze through tiny pores in the skin that normal vesicles cannot pass.
• This high elasticity makes transfersomes ideal for deep dermal and transdermal delivery.
• They can deliver macromolecules that usually struggle to cross the skin barrier.

For programs focusing on non-invasive delivery, transfersomes are a powerful option.

Niosomes

Niosomes resemble liposomes, but they use non-ionic surfactants instead of phospholipids.

• They are often more chemically stable and cost-effective than classic liposomes.
• They can also encapsulate both hydrophilic and lipophilic drugs.
• Researchers apply niosomes in dermal, ocular, and parenteral systems.

Niosomes are a practical lipid-based delivery strategy where cost, flexibility, and stability are key.

Proliposomes

Proliposomes are dry, free-flowing particles that form liposomes upon hydration.

• They improve the stability and handling of liposomal formulations.
• They are easier to store and transport.
• They are especially useful for oral and inhalation routes.

By converting to liposomes in situ, proliposomes merge manufacturing convenience with the benefits of liposomal delivery.

Transethosomes

Transethosomes are hybrid vesicles that combine features of ethosomes and transfersomes.

• They contain high ethanol content plus edge activators.
• This combination improves both penetration and flexibility.
• They are designed to overcome multiple skin barriers at once.

Transethosomes are an advanced tool among lipid-based delivery strategies for difficult dermal indications and large molecules.

Exosomes

Exosomes are natural extracellular vesicles released by cells.

• They carry proteins, lipids, and nucleic acids as part of normal cell communication.
• Because they are "native" carriers, they offer interesting biocompatibility.
• They are being explored for RNA, protein, and small molecule delivery.

Although still under intensive research, exosomes represent a biologically inspired lipid delivery platform.

Emulsomes

Emulsomes are vesicular systems with a solid or semi-solid lipid core and a phospholipid shell.

They combine features of emulsions and liposomes.

They can improve the stability and loading of lipophilic drugs.

Emulsomes are investigated for systemic and targeted delivery.

They are especially useful when a classic emulsion is not stable enough or cannot carry enough payload.

3. Lipid Particulate System Category

This category includes solid or semi-solid lipid particles, offering controlled release and high stability.

Lipid Nanoparticles (LNPs)

LNPs are solid or semi-solid lipid particles, usually in the nanometer range.

• They often contain ionizable lipids, helper lipids, cholesterol, and PEGylated lipids.
• LNPs are now a leading platform for mRNA and siRNA delivery.
• They protect fragile nucleic acids and help them cross biological barriers.

After the success of mRNA vaccines, LNPs became a key focus for many pharmaceutical and biotech R&D teams.

Lipoplexes

Lipoplexes are complexes formed between cationic lipids and negatively charged nucleic acids.

• They rely on electrostatic interactions to condense DNA or RNA.
• They facilitate cell uptake and endosomal escape.
• However, they require careful optimization to balance efficiency and toxicity.

Lipoplexes are an important class of lipid-based delivery strategies for gene delivery research.

Solid Lipid Nanoparticles (SLNs)

SLNs are nanoparticles made from lipids that are solid at room and body temperature.

• They provide a solid matrix that can hold lipophilic drugs.
• They offer controlled or sustained release profiles.
• They show good physical stability and are suitable for various routes (oral, dermal, parenteral).

SLNs allow formulators to combine the advantages of liposomes and polymeric nanoparticles while using physiologically acceptable lipids.

Nanostructured Lipid Carriers (NLCs)

NLCs are second-generation systems that mix solid lipids with liquid lipids.

• This mix creates a less ordered matrix with more space for the drug.
• As a result, NLCs can show higher loading capacity and reduced drug expulsion.
• They are widely explored for dermal, oral, and parenteral delivery.

When SLNs are limited by low loading or drug leakage, NLCs offer a more flexible alternative.

Core Advantages of Lipid-Based Delivery Strategies

Across all these systems, some common advantages stand out. Table 1 outlines the key benefits that make lipid-based delivery strategies a cornerstone of modern drug formulation, highlighting how they address critical challenges like solubility, stability, and bioavailability.

Table 1 Advantages of lipid-based delivery strategies.

Key Limitations and Challenges

However, these systems are not perfect. R&D teams must consider several issues. Table 2 details the hurdles that R&D teams must navigate when developing lipid-based delivery systems, from manufacturing complexities to regulatory and compatibility issues.

Table 2 Limitations of lipid-based delivery strategies.

Want to leverage lipid-based delivery's advantages while mitigating limitations?

Share your API properties, target route, and scalability needs with our Formulation Experts. We'll deliver a tailored assessment of key benefits for your molecule, risk mitigation strategies for challenges, and a roadmap to balance efficacy and manufacturability.

Where Lipid-Based Delivery Strategies Are Used

By leveraging its versatility in solubility enhancement, stability, and targeted delivery, lipid-based delivery is now used across many sectors.

Pharmaceuticals and Biotech

Small molecules with poor solubility: Over 40-70% of new drug candidates fall into this category. Lipid systems like SEDDS, nanoemulsions, and SLNs keep them dissolved or dispersed. For example, a SEDDS formulation of the anti-fungal drug griseofulvin improved its oral bioavailability by 3x.

Peptides and proteins: Fragile molecules like insulin, growth factors, and monoclonal antibodies are protected from enzymatic degradation and pH changes by lipid carriers. Liposomal insulin, for instance, avoids breakdown in the stomach, thereby enabling oral delivery research.

mRNA, siRNA, and DNA constructs: LNPs emerged as the gold standard for nucleic acid delivery. They shield RNA from nucleases, facilitate cellular uptake, and enable endosomal escape.

Vaccine antigens and adjuvant systems: Liposomes and lipid nanoparticles can act as carriers for vaccine antigens (e.g., influenza, HPV) and adjuvants, boosting immune responses by targeting antigen-presenting cells and prolonging antigen release.

Cosmetics and Personal Care

Active ingredients for anti-aging, moisturizing, and barrier repair: Transfersomes, ethosomes, and liposomes can deliver retinol, hyaluronic acid, and ceramides deep into skin layers. For example, retinol-loaded ethosomes can reduce wrinkles by 25% compared to conventional creams, as they penetrate the stratum corneum more effectively.

UV filters and antioxidants in sunscreens and creams: Lipid encapsulation of UV filters (e.g., avobenzone) and antioxidants (e.g., vitamin E) improves their photostability and reduces skin irritation. Nanoemulsion-based sunscreens also offer better spreadability and a lighter texture.

Food, Nutrition, and Supplements

Lipid-based encapsulation of vitamins, flavors, and nutraceuticals: Fat-soluble vitamins (A, D, E, K), omega-3 fatty acids, and plant extracts (e.g., curcumin) can be encapsulated in SLNs, nanoemulsions, or SEDDS to improve their solubility and absorption. For example, vitamin D-loaded nanoemulsions show 2x higher bioavailability than unencapsulated vitamin D.

Improved stability and controlled release in functional foods: Lipid carriers protect sensitive nutrients from heat, pH, and oxidation during food processing and digestion. Encapsulated probiotics in lipid matrices, for instance, survive stomach acid better and release slowly in the intestines. Flavor molecules (e.g., mint, citrus) are also encapsulated to mask bitterness or control release in functional beverages and snacks.

Want to boost your product's bioavailability with lipid-based delivery?

Share your active ingredient (drug, nutrient, or cosmetic compound) and target route (oral, dermal, ocular, etc.) with our Formulation Experts. We will craft a customized plan, including carrier selection, solubility testing, and bioavailability validation according to your product's unique needs.

What Formulation Scientists Track: Performance Metrics

To compare lipid-based delivery strategies, R&D teams usually monitor:

• Particle size and polydispersity index (PDI)
• Zeta potential for stability and interaction with membranes
• Encapsulation efficiency (EE%)
• Drug loading capacity
• In vitro release profiles
• Stability under stress conditions (temperature, light, agitation)
• Biological performance, such as permeability or uptake in relevant cell models

For partners like Creative Biolabs, these metrics guide optimization and platform selection for each project.

Why Creative Biolabs Cares About Lipid-Based Delivery Strategies

At Creative Biolabs, lipid-based delivery is closely connected to many advanced platforms, including targeted delivery, nanoformulation, and biologics research.

By combining:

• deep understanding of lipid systems such as liposomes, LNPs, SLNs, NLCs, nanoemulsions, and transethosomes,
• modern analytical and characterization tools, and
• flexible design of custom delivery platforms,

teams can explore more robust and data-driven formulation options for complex molecules.

Related Services You May Be Interested in

FAQs

Conclusion

Lipid-based delivery strategies have moved from niche academic ideas to core technologies in global drug development and advanced formulation. As molecules become more complex and routes more demanding, researchers need carriers that can protect, solubilize, and precisely deliver their actives.

From liposomes and LNPs to transethosomes, SEDDS, and Pickering emulsions, the landscape is rich and continues to expand. With the right partners and platforms, such as those offered by companies like Creative Biolabs, lipid-based systems will continue to shape the next generation of innovative delivery solutions worldwide.

For Research Use Only. Not for Clinical Use.

References

1. Baig, M. S. et al. "Lipid-based nanoparticles: innovations in ocular drug delivery." Front. Mol. Biosci. 11, 1421959 (2024). https://www.frontiersin.org/articles/10.3389/fmolb.2024.1421959/full.
2. Mohite, P., Singh, S., Pawar, A., Sangale, A. & Prajapati, B. G. "Lipid-based oral formulation in capsules to improve the delivery of poorly water-soluble drugs." Front. Drug Deliv. 3, 1232012 (2023). https://www.frontiersin.org/articles/10.3389/fddev.2023.1232012/full.
3. Shrestha, H., Bala, R. & Arora, S. "Lipid-Based Drug Delivery Systems." Journal of Pharmaceutics 2014, 1–10 (2014). https://www.hindawi.com/journals/jphar/2014/801820/. Distributed under Open Access license CC BY 4.0, without modification.

Our services are For Research Use Only. We do not provide services to individuals.