Spirulina Peptides in Nanoliposomes Accelerate Full-Thickness Wound Healing in Mice | Research

The takeaway

Spirulina protein-derived peptides encapsulated in nanoliposomes significantly accelerated wound healing in 162 mice by boosting blood vessel formation, collagen production, and cell growth.

158 nm nanoliposomes
The optimized particle size of spirulina peptide-loaded nanoliposomes that outperformed all other treatment groups for wound healing in mice

What the researchers found

Spirulina protein hydrolysate (SPH)-loaded nanoliposomes (NLPs) were successfully created with a particle size of 158 nm and zeta potential of -48 mV, indicating good stability. Key findings:

**In vitro**: SPH showed no toxicity to human fibroblast cells (HFFF-2) and actually increased cell growth. Scratch wound assays confirmed faster cell migration with SPH treatment.

**In vivo (162 mice, 9 groups)**: The SPH-NLP treated group showed superior results compared to blank gel, blank NLPs, and free SPH groups at all concentrations (2.5%, 5%, 10%):

- Higher wound contraction rates

- Increased epithelialization

- Greater fibroblast proliferation

- Elevated expression of bFGF (growth factor), CD31 (blood vessel marker), and COL1A (collagen)

The nanoliposome encapsulation enhanced peptide delivery and efficacy beyond free peptide application.

Why it matters

Chronic and slow-healing wounds affect millions of people, particularly those with diabetes or immune disorders. Current wound treatments are limited, and there's growing interest in natural peptide-based therapies. This study shows that spirulina — an inexpensive, widely available algae — can be processed into wound-healing peptides, and that nanoliposome delivery significantly enhances their effectiveness. This could lead to affordable, natural wound care products.

How the study worked

The study had three phases: (1) Spirulina protein was hydrolyzed into peptides and encapsulated in nanoliposomes, then characterized for size, charge, and morphology. (2) In vitro safety and efficacy was tested using MTT toxicity assays and scratch wound tests on human fibroblast cells. (3) In vivo wound healing was tested in 162 mice divided into 9 groups (blank gel, blank NLPs, three concentrations of free SPH, three concentrations of SPH-NLPs). Wound healing was assessed by contraction measurements, histopathology, and immunofluorescence staining for bFGF, CD31, and COL1A.

What this study cannot tell us

The study was conducted in mice, and wound healing differs significantly between rodents and humans — mice heal primarily by contraction, while humans rely more on re-epithelialization. The specific peptide sequences responsible for the healing effect were not identified. The optimal dose and application frequency for human wounds are unknown. Long-term safety of repeated nanoliposome application to wounds was not assessed. The study did not compare against established wound healing treatments.

How to read the evidence

This is a well-designed preclinical study with both in vitro and in vivo components using 162 mice across 9 groups. The large animal number and multiple assessment methods (histopathology, immunofluorescence) strengthen the findings. However, it remains an animal study without human clinical validation.

When this study was published

Published in 2023, this study reflects current trends in combining bioactive peptides with nanodelivery systems for wound healing applications.

The bigger picture

This study sits at the intersection of two growing fields: bioactive peptides from natural sources and nanoparticle drug delivery. Spirulina is already widely consumed as a nutritional supplement, and repurposing its protein content for wound healing adds pharmaceutical value. The nanoliposome delivery approach could be applied to other bioactive peptides to improve their stability and tissue penetration for various therapeutic applications.

Questions still open

Which specific peptide sequences from spirulina protein hydrolysate are responsible for the wound healing effect?
How would these nanoliposomal peptides perform in a diabetic wound model, where healing is most impaired?
Can the nanoliposome formulation be scaled up to a commercially viable wound dressing or topical product?

Common questions

What is spirulina and why are its peptides useful for healing?

Spirulina is a blue-green algae that's about 60-70% protein and is widely consumed as a nutritional supplement. When its protein is broken down into small peptides through enzymatic digestion, some of these fragments have biological activities that can stimulate cell growth, promote blood vessel formation, and boost collagen production — all key processes in wound healing.

Why were nanoliposomes used instead of just applying the peptides directly?

Nanoliposomes are tiny lipid-based particles (158 nm in this study) that protect peptides from degradation and help them penetrate into wound tissue more effectively. In this study, peptides encapsulated in nanoliposomes performed significantly better than the same peptides applied freely, showing that the delivery method matters as much as the active ingredient.

Read the original research

Nanoliposomal peptides derived from Spirulina platensis protein accelerate full-thickness wound healing.

International journal of pharmaceutics, 630, 122457

View on PubMed ↗Publisher’s paper ↗

Citation

Ebrahimi, Alireza; Reza Farahpour, Mohammad; Amjadi, Sajed; Mohammadi, Maryam; Hamishehkar, Hamed. (2023). Nanoliposomal peptides derived from Spirulina platensis protein accelerate full-thickness wound healing.. International journal of pharmaceutics, 630, 122457. https://doi.org/10.1016/j.ijpharm.2022.122457