Atorvastatin liposomes in a 3D-printed polymer film: a repurposing approach for local treatment of oral candidiasis
Open accessAbstract
Oral candidiasis (OC) is an opportunistic fungal infection, common amongst the elderly and the immunocompromised. Unfortunately, the therapeutic efficacy of common antifungals is imperiled by the rise of antifungal drug resistance. An alternative promising therapeutic option possibly contributing to antifungal therapy is drug repurposing. Herein, we aimed to employ novel pharmaceutical drug delivery for enhancing the emerging antifungal potential of the hypocholesterolemic drug atorvastatin (ATV). ATV-propylene-glycol-liposomes (ATV/PG-Lip) were prepared then integrated in 3D-printed (3DP) mucoadhesive films comprising chitosan, polyvinyl-alcohol and hydroxypropyl methylcellulose, as an innovative blend, for the management of OC. ATV/PG-Lip demonstrated good colloidal properties of particle size (223.3 ± 2.1 nm), PDI (0.12 ± 0.001) and zeta potential (-18.2 ± 0.3 mV) with high entrapment efficiency (81.15 ± 1.88%) and sustained drug release. Also, ATV/PG-Lip showed acceptable three-month colloidal stability and in vitro cytocompatibility on human gingival fibroblasts. The developed 3DP-films exhibited controlled ATV release (79.4 ± 1.4% over 24 h), reasonable swelling and mucoadhesion (2388.4 ± 18.4 dyne/cm 2). In vitro antifungal activity of ATV/PG-Lip was confirmed against fluconazole-resistant Candida albicans via minimum inhibitory concentration determination, time-dependent antifungal activity, agar diffusion and scanning electron microscopy. Further, ATV/PG-Lip@3DP-film exceeded ATV@3DP-film in amelioration of infection and associated inflammation in an in vivo oral candidiasis rabbit model. Accordingly, the results confirm the superiority of the fabricated ATV/PG-Lip@3DP-film for the management of oral candidiasis and tackling antifungal resistance. Graphical abstract
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ATV-loaded liposomes (ATV-Lip) have a size of 223.3 ± 2.1 nm, polydispersity index of 0.12 ± 0.001, zeta potential of −18.2 ± 0.3 mV, encapsulation efficiency of 81.15 ± 1.88%, and provide controlled drug release over 24 h.
“ATV‐Lip exhibited suitable characteristics in terms of size (223.3 ± 2.1 nm), polydispersity index (0.12 ± 0.001), zeta potential (−18.2 ± 0.3 mV), and encapsulation efficiency (81.15 ± 1.88%), and provided controlled drug release over 24 h.”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [138]
Table 1 in Results and discussion (page not provided) gives the claimed size, PDI, and entrapment efficiency for the selected liposomes; the Stability testing section gives the claimed zeta potential. The In vitro drug release section reports controlled release from the liposomes, but its liposome comparison is at 6 hours. The claim’s 24-hour duration is not established for the liposomes themselves. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThere is a notable scarcity of published studies on integrating nanotechnology with statin therapy, indicating a significant gap in the current research landscape.
“However, there is a notable scarcity of published studies on this topic, indicating a significant gap in the current research landscape [138].”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [138]
The Introduction identifies a narrower gap: propylene glycol liposomes had not previously been investigated for buccal drug delivery, and nanodrug delivery of atorvastatin for antifungal use could be further explored. It does not establish a general scarcity of published studies combining nanotechnology with statin therapy; the References include an earlier study of atorvastatin-loaded liposomes. (LLM, conf=0.82)
Experimental — accuracy not yet measuredATV-Lip are superior to free ATV against fluconazole-resistant C. albicans in the time-kill assay, but free ATV gives better results in minimum inhibitory concentration and agar diffusion assays.
“In vitro antifungal activity of the ATV‐Lip against fluconazole‐resistant C. albicans was superior to free ATV in the time‐kill assay. However, in the determination of the minimum inhibitory concentration and in the agar diffusion assay, better results were reported for the free ATV.”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [138]
The Results and discussion section reports lower fungal growth with ATV/PG-Lip than free ATV in the time-dependent assay, and lower MICs for free ATV. In the agar diffusion assay, free ATV had a slightly larger inhibition zone, but the difference from ATV/PG-Lip was not statistically significant; describing free ATV as giving better results in that assay overstates the finding. (LLM, conf=0.87)
Experimental — accuracy not yet measuredIn vivo assays using a rabbit OC model demonstrate enhanced antifungal activity and a significant reduction in inflammation for ATV-Lip films compared to other treatment groups.
“Despite this, in vivo assays using a rabbit OC model demonstrated enhanced antifungal activity and a significant reduction in inflammation for the films compared to other treatment groups.”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [138]
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- Authors
- Nour, E. M., El-Habashy, S. E., Shehat, M. G., Essawy, M. M., El-Moslemany, R. M., & Khalafallah, N. M.
- Affiliations
- Alexandria University (EG)
- Corresponding author
- El-Habashy, Salma E.
- ORCID
- Venue
- Drug Delivery and Translational Research
- Published
- 2023-05-15
- Volume
- 13
- Issue
- 11
- Pages
- 2847-2868
- ISSN
- 2190-393X (ISSN-L)
- 2190-3948
- PMC
- PMC10545585
- OpenAlex
- W4376609793
- Cited by
- 41
- References
- 59
- Citations by year
- 2026: 8 · 2025: 20 · 2024: 8 · 2023: 5
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Drug Delivery and Translational Research (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Greater South Information System
- Funders
- Alexandria University
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- oral candidiasis, atorvastatin, drug repurposing, liposomes, propylene glycol, chitosan, polyvinyl alcohol, hydroxypropyl methylcellulose, antifungal resistance, Candida albicans, fluconazole resistance, sustained drug release, mucoadhesion, rabbit model
- MeSH terms
- Atorvastatin, Aged, Animals, Antifungal Agents, Candidiasis, Oral, Humans, Liposomes, Polymers, Rabbits, Drug Repositioning, Printing, Three-Dimensional
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