Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery

Lipid-polymer hybrid nanoparticles (LPHNPs) represent an advanced core–shell nanocarrier system combining the structural stability of a polymeric core with the biocompatibility and surface functionality of a lipid shell. The polymeric matrix, often formed from biodegradable polyesters such as poly(lactic-co-glycolic acid) (PLGA), ensures sustained drug release and mechanical integrity, while the lipid envelope facilitates high drug loading, reduced opsonisation and prolonged circulation. Surface modification via polyethylene glycol (PEG) conjugation or targeting ligands such as peptides and antibodies confers active targeting to specific cell types and tissues. Stimuli-responsive moieties incorporated into the shell can trigger on-demand release in response to pH, temperature or enzymatic activity. Collectively, these design principles enable the delivery of chemotherapeutics, anti-inflammatory agents and natural products with improved therapeutic index, reduced off-target toxicity and the potential to overcome biological barriers including the blood–brain barrier and hepatic clearance. LPHNPs have been applied across oncology, immunotherapy, central nervous system disorders and regenerative medicine, demonstrating global significance in precision medicine and paving the way for translation into clinical settings.

Research from Nature Portfolio

Core–shell LPHNPs combining a PLGA core with a lipid layer encapsulating docetaxel and a sphingosine kinase inhibitor have been shown to re-sensitise resistant prostate cancer cells. Nanoparticle encapsulation enabled a fourfold reduction in drug dose while maintaining antitumour efficacy, enhanced tumour accumulation and markedly reduced systemic toxicity in murine models. The steady cellular uptake and sustained intracellular release profile underpinned superior in vitro and in vivo performance compared with free drug combinations.
Another study formulated β-sitosterol into LPHNPs using PLGA and DSPE-PEG lipids at optimised ratios, achieving high entrapment efficiency and sub-200 nm particle size. In a rat model of carbon tetrachloride-induced hepatotoxicity, these nanoparticles restored biochemical markers of liver function, preserved histological architecture and suppressed apoptotic signalling, thereby demonstrating potent hepatoprotective effects of a naturally derived compound when delivered via an LPHNP platform.

Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery publication trend

The graph below shows the total number of articles in lipid-polymer hybrid nanoparticles for targeted drug delivery across all publications each year (not limited to Nature Index journals).

Technical terms

Lipid-polymer hybrid nanoparticle (LPHNP): A nanocarrier with a polymeric core enclosed by a lipid shell, combining the advantages of both materials for drug delivery.

Core–shell architecture: A structural design in which an inner core (often polymeric) is surrounded by an outer shell (lipid or lipid–PEG), enabling compartmentalised drug loading and release.

PEGylation: Surface modification of nanoparticles with polyethylene glycol chains to enhance aqueous stability, reduce immune recognition and prolong systemic circulation.

Targeting ligand: A molecule (e.g. peptide, antibody fragment) attached to the nanoparticle surface that binds selectively to receptors on target cells, facilitating active targeting.

Stimuli-responsive moiety: A functional group within the nanoparticle shell that undergoes structural change or degradation in response to specific triggers (pH, enzymes, temperature), enabling controlled drug release.

References

1. Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer. Scientific Reports (2017).
2. Assessment of the hepatoprotective effect of developed lipid-polymer hybrid nanoparticles (LPHNPs) encapsulating naturally extracted β-Sitosterol against CCl4 induced hepatotoxicity in rats. Scientific Reports (2019).
3. Lipid polymer hybrid nanoparticles: a custom-tailored next-generation approach for cancer therapeutics. Molecular Cancer (2023).
4. PEG–Lipid–PLGA Hybrid Particles for Targeted Delivery of Anti-Inflammatory Drugs. Pharmaceutics (2024).
5. Hesperidin-Loaded Lipid Polymer Hybrid Nanoparticles for Topical Delivery of Bioactive Drugs. Pharmaceuticals (2022).