# Fabrication and Detailed Characterization of PLA/PEG Composite Nanofibers for the Co-Delivery and Synergistic Release of Quercetin and Rosmarinic Acid via Electrospinning

**Authors:** Nikoleta Stoyanova, Ani Georgieva, Reneta Toshkova, Mariya Spasova

PMC · DOI: 10.3390/molecules31040704 · Molecules · 2026-02-18

## TL;DR

Researchers created a new drug delivery system using nanofibers to improve the effectiveness of two natural compounds for treating cancer and other conditions.

## Contribution

A novel electrospun PLA/PEG nanofiber platform for co-delivering quercetin and rosmarinic acid with controlled release and enhanced stability.

## Key findings

- The nanofibers achieved a biphasic release profile with an initial burst followed by sustained release.
- The material showed high anticancer activity against melanoma cells with low toxicity to normal cells.
- PLA/PEG nanofibers provided uniform morphology and high entrapment efficiency for both polyphenols.

## Abstract

Natural polyphenols, particularly quercetin (QUE) and rosmarinic Acid (RA), possess significant synergistic therapeutic potential as potent antioxidants and anti-inflammatories. However, their poor stability, low water solubility, and resulting limited bioavailability severely hinder their effective clinical translation. This study addresses these fundamental limitations by designing a novel advanced drug delivery platform utilizing electrospinning. We have fabricated composite high-molecular-weight poly(L-Lactic Acid) (PLA)/polyethylene glycol (PEG) nanofibers for the simultaneous co-delivery of both QUE and RA, optimizing compound stability and release kinetics. PLA provided mechanical integrity and sustained release properties, while the incorporation of PEG strategically enhanced the mat’s wettability, enabling precise control over initial drug dissolution. Comprehensive characterization confirmed uniform, bead-free morphology and high entrapment efficiency for both polyphenols. Crucially, the PLA/PEG blend successfully achieved a biphasic release profile, featuring an initial burst release mediated by PEG followed by a sustained release phase governed by the PLA matrix. Furthermore, the performed in vitro investigations using SH-4 melanoma cells and HaCaT normal keratinocytes revealed that the prepared novel materials containing the polyphenols possessed high anticancer activity to the used cancer cell line. However, the toxicity to the normal cell line is much lower. Therefore, this novel electrospun composite scaffold offers an effective strategy to enhance the stability, control the delivery, and maximize the synergistic therapeutic benefits of quercetin and rosmarinic Acid for applications in areas such as advanced wound care, tissue regeneration, and antitumor therapies.

## Linked entities

- **Chemicals:** quercetin (PubChem CID 5280343), rosmarinic Acid (PubChem CID 639655), polyethylene glycol (PubChem CID 9033)
- **Diseases:** melanoma (MONDO:0005105)

## Full-text entities

- **Diseases:** injury to (MESH:D014947), inflammation (MESH:D007249), melanoma (MESH:D008545), Cancer (MESH:D009369), Cytotoxicity (MESH:D064420), necrotic (MESH:D009336)
- **Chemicals:** O (MESH:D010100), formazan (MESH:D005562), RA (MESH:C041376), AO (MESH:D000165), methanol (MESH:D000432), gold (MESH:D006046), ester (MESH:D004952), C (MESH:D002244), streptomycin (MESH:D013307), polymer (MESH:D011108), EtBr (MESH:D004996), hydroxycinnamic acid (MESH:D003373), EDTA (MESH:D004492), paclitaxel (MESH:D017239), PEG (MESH:D011092), DCM (MESH:D008752), QUE (MESH:D011794), benzene (MESH:D001554), Water (MESH:D014867), EtOH (MESH:D000431), NaOH (MESH:D012972), acetic acid (MESH:D019342), penicillin (MESH:D010406), Glacial (-), polyester (MESH:D011091), MTT (MESH:C070243), PLA (MESH:C033616), Polyphenols (MESH:D059808), CO2 (MESH:D002245), L-glutamine (MESH:D005973), flavonoid (MESH:D005419), DMSO (MESH:D004121), reactive oxygen species (MESH:D017382), acetate (MESH:D000085), Tween 80 (MESH:D011136), H (MESH:D006859)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** SH-4 — Homo sapiens (Human), Embryonic stem cell (CVCL_C724), CRL-7724 — Sigmodon hispidus (Hispid cotton rat), Spontaneously immortalized cell line (CVCL_YD58), HaCaT — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_0038), 3T3 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0594), HeLa — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), CVCL_0038 — Homo sapiens (Human), Finite cell line (CVCL_7271)

## Full text

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## Figures

11 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942796/full.md

## References

49 references — full list in the complete paper: https://tomesphere.com/paper/PMC12942796/full.md

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Source: https://tomesphere.com/paper/PMC12942796