Palm Oil and Myristic Acid Nanoparticles Could Smooth Out Parkinson’s Drug Delivery

Parkinson’s disease is one of the fastest-growing neurodegenerative disorders in the world, and its frontline treatment has barely changed in half a century. Levodopa, or L-DOPA, remains the gold-standard drug for controlling the tremors, rigidity, and slowness of movement that define the condition, yet the molecule itself is a notoriously difficult passenger inside the body. It is rapidly metabolized in the periphery before much of it reaches the brain, and the plasma concentrations that result swing wildly between doses, leaving patients to oscillate between mobility and immobility in a phenomenon known as wearing-off. A team of researchers from Universitas Pendidikan Indonesia and collaborating institutions now reports a formulation strategy that could help tame this erratic behavior, using two of the most abundant and inexpensive natural lipids available: solid myristic acid and liquid palm oil.

The study, published in the journal Results in Chemistry, describes the design and characterization of a lipid nano-emulsion, abbreviated LNE-MP, in which L-DOPA is encapsulated within a blended lipid matrix. Lipid nano-emulsions belong to a broader family of lipid-based nanocarriers that have attracted intense interest in pharmaceutical science because they are biocompatible, biodegradable, and capable of hosting both water-loving and fat-loving drugs. What distinguishes the new work is its deliberate use of natural, sustainable lipid sources rather than synthetic excipients, and its systematic screening of the formulation variables that determine whether the resulting particles are small enough, uniform enough, and stable enough to be medically useful.

The underlying materials logic is elegant. A lipid carrier built purely from solid lipid tends to crystallize into a highly ordered lattice upon cooling, leaving little room for drug molecules to lodge inside. Incorporating a liquid lipid disrupts that ordered packing, creating structural imperfections and voids that can accommodate the drug during recrystallization. Myristic acid, a saturated fatty acid, was chosen as the solid component because it is biocompatible and forms a stable matrix after cooling, and because its free carboxylic group offers polar interaction sites for the hydroxyl, amino, and carboxyl functionalities of L-DOPA, favoring non-covalent drug-lipid association. Palm oil, a sustainable and cost-effective liquid lipid, was selected to supply the disordering fraction of the blend.

Manufacturing the particles involved two sequential steps. First, the lipid mixture, drug, and the nonionic surfactant Tween 80 were subjected to hot homogenization at 1500 revolutions per minute and 55 degrees Celsius for one hour, a temperature safely above the melting point of myristic acid. The resulting coarse emulsion was then refined by ultrasonication, with the team varying sonication time between 40 and 80 minutes and sonication power between 50 and 100 percent. Maltodextrin served as a drying adjuvant during spray drying, converting the liquid nano-dispersion into a structured, storable solid. The screening was conducted sequentially: first the ratio of myristic acid to palm oil was fixed, then surfactant concentration and ultrasonic parameters were tuned.

The ratio screening proved decisive for stability. Formulations with higher proportions of solid lipid, from a 5:5 blend down to 2:8, promoted particle aggregation and phase separation during thermal processing, while pushing the solid fraction below ten percent eroded the mechanical rigidity of the matrix and destabilized the dispersion once again. Only the 1:9 ratio of myristic acid to palm oil yielded a stable dispersion free of coagulation and phase separation after 24 hours of storage, striking the balance between matrix rigidity and liquid-lipid disorder that the colloidal stability of the carrier requires.

With the composition locked in, the processing variables revealed a clear hierarchy of influence. Raising the Tween 80 concentration from 1.5 to 2.0 percent had a more dramatic effect on particle size than any adjustment of sonication, driving the mean diameter from around 110 nanometers down to the 81 to 91 nanometer range. The surfactant lowers surface tension, stabilizing the spherical droplets formed during ultrasonic cavitation before they can recoalesce. The finest and most uniform product, with a mean size of roughly 85 to 86 nanometers and a polydispersity index as low as 0.10, emerged from the combination of 2 percent Tween 80, 80 minutes of sonication, and 50 percent power. Notably, excessive energy input was counterproductive: higher sonication power broadened the size distribution, because intense cavitation can fragment droplets only for them to remerge.

Characterization confirmed that the optimized particles were not merely small but colloidally robust. The zeta potential, a measure of surface charge, came in at approximately minus 40 millivolts, well beyond the minus 30 millivolt threshold generally associated with strong electrostatic repulsion between droplets and high physical stability in nanosuspensions. The negative charge arises from the ionization of acidic groups in the lipid components and the orientation of the nonionic surfactant at the particle surface, which generates an electrical double layer. In drug delivery, a moderately high negative surface charge carries a further advantage: it tends to reduce nonspecific protein adsorption and opsonization compared with cationic particles, potentially extending circulation time and improving biocompatibility.

Spectroscopy and microscopy filled in the molecular picture. Fourier transform infrared spectra of the loaded particles retained the characteristic aliphatic carbon-hydrogen stretches near 2920 to 2850 wavenumbers and the ester carbonyl band near 1740 to 1750 wavenumbers of the lipid matrix, indicating that the carrier’s chemical structure survived formulation intact. Meanwhile, the hydroxyl and amine bands characteristic of pure L-DOPA broadened and shifted in the loaded formulation, evidence that the drug’s functional groups engage in non-covalent interactions with the lipids. Crucially, no new absorption bands appeared, suggesting no chemical transformation of the drug within the sensitivity of the technique. Transmission electron microscopy showed nearly spherical particles with low aspect ratio and little clustering, consistent with the light-scattering data, while energy-dispersive X-ray spectroscopy detected only carbon, oxygen, and nitrogen, in approximate atomic proportions of 72, 25, and 3 percent, the nitrogen being the fingerprint of incorporated L-DOPA and the absence of other elements confirming high chemical purity.

Functionally, the formulation encapsulated roughly half of the initial L-DOPA payload, an efficiency the authors acknowledge will require further optimization if higher loading is pursued. The release behavior, however, is where the design shows its therapeutic promise. In dialysis-bag experiments conducted over eight hours, cumulative release climbed to about 27 percent at the intestinal pH of 7.4 and about 20 percent at the gastric pH of 1.2 after six hours, with no sudden burst release at either condition. The higher release at physiological pH reflects the differing solubility and ionization of L-DOPA and pH-dependent hydration of the particle surface. Kinetic modeling showed the profile fit a zero-order model best at pH 7.4, meaning release was governed more by the structural characteristics of the lipid carrier than by the remaining drug concentration, exactly the behavior desired for smoothing plasma fluctuations and reducing dosing frequency. The Korsmeyer-Peppas diffusion exponents fell in the anomalous transport range, though the authors treat that interpretation as preliminary given the model’s weaker fit.

The work remains at the in vitro stage, and the authors themselves note that chromatographic verification by high-performance liquid chromatography and additional solid-state studies by differential scanning calorimetry and X-ray diffraction are needed before the platform can advance. Even so, the demonstration that a sub-100-nanometer, narrowly distributed, electrostatically stabilized L-DOPA carrier can be built from myristic acid and palm oil, two cheap and abundant natural feedstocks, using nothing more exotic than homogenization and sonication, is a meaningful contribution to affordable nanomedicine. For a disease whose prevalence is rising steeply and whose patients depend on precise, steady dopaminergic dosing, a delivery platform that promises sustained release, reduced peripheral waste, and improved tolerability, manufactured from sustainable ingredients, offers a compelling glimpse of where Parkinson’s pharmacotherapy may be heading next.

Subject of Research: Lipid nano-emulsion formulation of myristic acid and palm oil for L-DOPA delivery in Parkinson's disease

Article Title: Efficient delivery of L-DOPA through lipid nano-emulsion formulation using solid myristic acid and liquid palm oil

Article References: Sardjono, R. E., Chyntia, A., Nuraini, V. A., Gunawan, R., Kadarohman, A., Ray, H. R. D., Vikasari, S. N., Erdiwansyah, Fatimah, S., & Ko, Y. G. (2026). Efficient delivery of L-DOPA through lipid nano-emulsion formulation using solid myristic acid and liquid palm oil. Results in Chemistry, 31, Article 103937. https://doi.org/10.1016/j.rechem.2026.103937

Image Credits: AI Generated

DOI: 10.1016/j.rechem.2026.103937

Keywords: L-DOPA, lipid nano-emulsion, myristic acid, palm oil, Parkinson's disease, drug delivery, nanoparticles, encapsulation efficiency, zeta potential, controlled release, Tween 80, sonication