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Cited by 32Advancements in Transdermal Drug DeliveryDrug Solubulity and Delivery SystemsSkin Protection and Aging

High-Payload Nanosuspension of Centella asiatica Extract for Improved Skin Delivery with No Irritation

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Kim, Eun A, Park, Jun Soo, Kim, Min Seop, Jeong, Min Young, Park, Hyun Jin, Choi, Jun Hyuk, Seo, Jae Hee, Choi, Yong Seok +1 more·2021·International Journal of Nanomedicine
DOI 10.2147/ijn.s335039PMC PMC8573141
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Abstract

BACKGROUND: (CA) has received much attention as a cosmeceutical ingredient owing to its anti-wrinkle effect. However, due to the low solubility and high molecular weight of pharmacologically active constituents, including asiatic acid (AA), madecassic acid (MA), and asiaticoside (AS), it is challenging to fabricate high-payload topical preparations of CA with satisfactory skin absorption profiles. PURPOSE: This study aimed to design a high-payload topical preparation of CA using nanocrystallization technique and to evaluate its skin absorption profile and local tolerability. METHODS: High-payload nanocrystal suspensions (NSs) were prepared using lab-scale bead-milling technology, by adjusting the type and amount of suspending agent, CA content, type of vehicle, and milling speed. CA-loaded NSs were characterized in terms of morphology, particle size, crystallinity, and in vitro dissolution pattern. Skin absorption of CA nanocrystals was evaluated using a vertical Franz diffusion cell mounted with porcine skin. In vivo skin irritation following topical application of high-payload NS was assessed in normal rats. RESULTS: The optimized NS system, composed of 10% (w/v) CA, 0.5% polyvinylpyrrolidone (PVP) K30 as steric stabilizer, and 89.5% of distilled water, was characterized as follows: spherical or elliptical in shape, 200 nm in size, with low crystallinity. The in vitro dissolution of AA or MA from NSs was markedly faster compared to raw material, under sink condition. Penetration of AA, MA, and AS in the porcine skin was markedly elevated using the high-payload NS formula, providing 5-, 4-, and 4.5-fold higher accumulation in skin layer, compared to that of the marketed cream formula (CA 1%, Madeca cream). Moreover, topical application of high-payload NS was tolerable, showing neither erythema nor oedema in normal rats. CONCLUSION: The novel NS system is expected to be a virtuous approach for offering a better skin absorption of CA, without using an excess quantity of solubilizers.

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  • Asiaticoside and madecassoside activate the TGF-β/Smad pathway to drive extracellular matrix synthesis, thereby enhancing collagen deposition and improving skin elasticity and hydration.

    “At the molecular signaling level, asiaticoside and madecassoside activate the TGF-β/Smad pathway to drive extracellular matrix synthesis, thereby enhancing collagen deposition and improving skin elasticity and hydration (Shen et al. 2019; Kim et al. 2021; Tai et al. 2025).”

    From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Kim et al. 2021

    The Introduction (page not provided) says topical Centella asiatica activates Smad signaling and increases type I collagen production. It does not attribute that mechanism to both asiaticoside and madecassoside, establish increased extracellular matrix synthesis or collagen deposition, or link the pathway to improved skin elasticity and hydration. The paper identifies madecassic acid as a principal constituent, not madecassoside. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Triterpenoid saponins from C. asiatica, upon hydrolysis, yield aglycones that promote collagen and hyaluronic acid synthesis, exhibit anti-inflammatory and anti-elastase activities, and possess antioxidative properties critical for scar control and anti-aging benefits.

    “Central to the pharmacological activity of C. asiatica are triterpenoid saponins, which upon hydrolysis yield aglycones that promote collagen and hyaluronic acid synthesis, exhibit anti-inflammatory and anti-elastase activities, and possess antioxidative properties critical for scar control and anti-aging benefits (Shen et al. 2019; Kim et al. 2021; Chutoprapat et al. 2024; Zhang et al. 2024; Alam”

    From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Kim et al. 2021

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • NLCs containing asiaticoside penetrated the stratum corneum more effectively than free extracts, yielding a 50-60% increase in biological activity, especially in collagen stimulation and wound contraction.

    “NLCs containing asiaticoside penetrated the stratum corneum more effectively than free extracts, yielding a 50–60% increase in biological activity – especially in collagen stimulation and wound contraction (da Rocha et al. 2019; Kim et al. 2021; Krzyżostan et al. 2024).”

    From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Kim et al. 2021

    In Results and Discussion, the paper reports increased asiaticoside accumulation in porcine skin with Centella asiatica nanosuspensions and cites a report of greater skin accumulation with solid lipid nanoparticles. It does not establish the claimed comparison of NLCs with free extracts or a 50–60% increase in biological activity, collagen stimulation, or wound contraction. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • SLNs, NLCs, nanoemulgels, and SLMs have been extensively utilized to encapsulate C. asiatica actives.

    “Solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoemulgels, and solid lipid microparticles (SLMs) have been extensively utilized to encapsulate C. asiatica actives.”

    From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Kim et al. 2021

    The Introduction (page unavailable) says lipid nanoparticles are among approaches used to improve delivery of Centella asiatica actives, and reference 16 identifies a study of Centella asiatica-loaded lipid nanoparticles. Our copy does not establish that all four named formulation types—SLNs, NLCs, nanoemulgels, and SLMs—have been extensively used for encapsulation. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • A study utilizing a C. asiatica-infused facial mask for rosacea management reported improved barrier integrity, reduced flare-ups, and no adverse events.

    “For instance, a study utilizing a C. asiatica–infused facial mask for rosacea management reported improved barrier integrity, reduced flare-ups, and no adverse events (Kim et al. 2021).”

    From Centella asiatica (L.) Urb. in skin health and cosmeceuticals: mechanisms, clinical evidence, and advanced delivery systems (2025) · cites this paper as Kim et al. 2021

    The Results and Discussion section (page not provided) reports no erythema or oedema during a five-day test of Centella asiatica nanosuspensions in normal rats. That supports a limited no-irritation finding, not a claim of no adverse events in people. The paper does not report a facial-mask study in rosacea patients or improvements in barrier integrity or flare-ups. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Kim, E. A., Park, J. S., Kim, M. S., Jeong, M. Y., Park, H. J., Choi, J. H., Seo, J. H., Choi, Y. S., & Kang, M. J.
Affiliations
Dankook University (KR)
Corresponding author
Kang, Myung Joo
ORCID
Venue
International Journal of Nanomedicine
Publisher
Informa UK Limited
Published
2021-11
Volume
Volume 16
Pages
7417-7432
ISSN
  • 1176-9114 (ISSN-L)
  • 1178-2013
DOI
10.2147/ijn.s335039
PMC
PMC8573141
OpenAlex
W3209185343
Cited by
32
References
4
Citations by year
2026: 6 · 2025: 8 · 2024: 8 · 2023: 6 · 2022: 4
FWCI
1.83
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Nanomedicine (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
Funders
  • National Research Foundation
  • National Research Foundation of Korea (NRF-2019R1C1C1004211)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
  • Health Sciences › Medicine › Dermatology › Skin Protection and Aging
Keywords
Centella asiatica, nanoparticle suspensions, nanocrystallization, asiatic acid, madecassic acid, asiaticoside, percutaneous absorption, topical drug delivery, skin irritation, bead milling, polyvinylpyrrolidone K30, porcine skin, in vitro dissolution
MeSH terms
Animals, Plant Extracts, Skin, Skin Absorption, Suspensions, Triterpenes, Centella, Rats

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