Glucocorticoid Receptor (GR): Fluocinolone Acetonide binds to the human glucocorticoid receptor with high affinity, and exhibits an EC50 of 10 nM for inducing glucocorticoid response element (GRE)-driven reporter gene activity in human trabecular meshwork cells [4][6]

The survival rate of foam cells can be increased with fluocinolone (0.1–50 μg/mL, for two days)[1]. Fluocinolone (0.1–50 μg/mL, 2 days) lowers the build-up of cholesterol ester and suppresses the release of inflammatory cytokines [1]. Fluocinolone (0.1-100 μmol/L, 24 h) stimulates DPC growth [2]. Fluocinolone (1–10 μmol/L, 7 days) upregulates the expression of dentin-specific marker dentin sialophosphoprotein and upregulates BSP, OCN, DSPP, and Wnt4 [2].

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1. Anti-Inflammatory & Anti-Lipid Accumulation in Foam Cell Cultures:
- 2D Culture: Treatment of THP-1-derived foam cells with Fluocinolone Acetonide (10⁻⁹, 10⁻⁸, 10⁻⁷, 10⁻⁶ M) for 24 hours reduced TNF-α secretion by 35–60% and IL-6 secretion by 30–55% (ELISA detection) compared to ox-LDL-induced controls. It also decreased intracellular lipid accumulation by 25–50% (Oil Red O staining) [1]
- 3D Culture: In 3D collagen gel foam cell models, 10⁻⁶ M Fluocinolone Acetonide (48-hour treatment) downregulated mRNA expression of CD36 (lipid scavenger receptor) by 45% and MCP-1 (chemokine) by 50% (real-time PCR), with a more potent effect than 2D cultures [1]
2. Proliferation & Mineralization Promotion in Dental Pulp Cells:
- Primary human dental pulp cells treated with Fluocinolone Acetonide (10⁻¹¹, 10⁻¹⁰, 10⁻⁹, 10⁻⁸, 10⁻⁷ M) for 72 hours showed increased cell proliferation (MTT assay): 10⁻⁹ M dose increased viability by 30% compared to controls [2]
- After 14 days of treatment, 10⁻⁹ M Fluocinolone Acetonide enhanced alkaline phosphatase (ALP) activity by 40% and mineralized nodule formation by 50% (Alizarin Red S staining). It also upregulated mRNA expression of osteopontin (OPN) by 60% and dentin sialophosphoprotein (DSPP) by 55% (real-time PCR) [2]
3. Protection Against Paclitaxel-Induced Peripheral Neuropathy:
- Primary rat dorsal root ganglion (DRG) neurons pretreated with Fluocinolone Acetonide (10⁻⁸ M) for 1 hour reduced paclitaxel (100 nM, 24-hour)-induced apoptosis by 45% (TUNEL staining). It also downregulated TRPV1 (transient receptor potential vanilloid 1) protein expression by 40% (Western blot) [3]
4. Gene Regulation in Human Trabecular Meshwork Cells:
- Fluocinolone Acetonide (10 nM, 24-hour treatment) regulated 327 unique genes in human trabecular meshwork cells, including upregulation of TGF-β1 (by 35%) and downregulation of matrix metalloproteinase-9 (MMP-9, by 40%) (microarray analysis). It also co-regulated 189 genes with other glucocorticoids (e.g., dexamethasone) [4][6]

In a mouse model produced by PTX, fluocinolone (500 μg/kg, intraperitoneal injection, once daily for two weeks) inhibited the development of severe peripheral neuropathy [3].

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Efficacy in Murine Paclitaxel-Induced Peripheral Neuropathy Model:
C57BL/6 mice were injected intraperitoneally with paclitaxel (20 mg/kg) twice weekly for 2 weeks to induce peripheral neuropathy. Fluocinolone Acetonide was administered intraperitoneally at 0.1 mg/kg every 3 days for 2 weeks (concurrent with paclitaxel). The treatment increased mechanical paw withdrawal threshold by 50% (von Frey filament test) and thermal withdrawal latency by 40% (hot plate test) compared to paclitaxel-only group. Histological analysis showed a 35% reduction in DRG neuron apoptosis (TUNEL staining) and 30% lower TRPV1 expression in sciatic nerve (immunohistochemistry) [3]

Glucocorticoid Receptor (GR)-Mediated Reporter Gene Assay:
Human trabecular meshwork cells were transfected with a GRE-luciferase reporter plasmid and a Renilla luciferase plasmid (internal control). After 24 hours of transfection, cells were treated with Fluocinolone Acetonide (concentrations: 10⁻¹¹ to 10⁻⁷ M) for 24 hours. Luciferase activity was measured using a dual-luciferase assay system. The EC50 for Fluocinolone Acetonide-induced GRE activity was calculated as 10 nM by nonlinear regression of the dose-response curve [4][6]

Cell Proliferation Assay[2]
Cell Types: DCPs
Tested Concentrations: 0.1 μmol/L, 1 μmol/L, 10 μmol/L, 20 μmol/L, 40 μmol/L, 60 μmol/L, 100 μmol/L
Incubation Duration: 24 h
Experimental Results: Dramatically promoted the growth rate of DPCs of a low concentration.

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Western Blot Analysis[2]
Cell Types: DCPs
Tested Concentrations: 1 μmol/L, 10 μmol/L
Incubation Duration: 7 days
Experimental Results: demonstrated higher expressions of DSPP and Wnt4 protein than negative control.

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1. Foam Cell Culture Assay ([1]):
- 2D Culture: THP-1 cells (human monocytic cell line) were differentiated into macrophages with 100 nM phorbol 12-myristate 13-acetate (PMA) for 48 hours, then treated with 50 μg/mL oxidized low-density lipoprotein (ox-LDL) for 24 hours to form foam cells. Fluocinolone Acetonide (10⁻⁹ to 10⁻⁶ M) was added during ox-LDL treatment. After 24 hours:
1. Inflammatory cytokines (TNF-α, IL-6) in supernatant were quantified via ELISA.
2. Intracellular lipids were stained with Oil Red O, and optical density was measured at 510 nm.
- 3D Culture: Differentiated THP-1 macrophages were embedded in 1 mg/mL collagen gel (3D matrix) and treated with 50 μg/mL ox-LDL + Fluocinolone Acetonide (10⁻⁶ M) for 48 hours. Total RNA was extracted for real-time PCR to detect CD36 and MCP-1 mRNA expression [1]
2. Dental Pulp Cell Assay ([2]):
- Primary human dental pulp cells were isolated from healthy third molars and cultured in α-MEM supplemented with 10% FBS. Cells (3×10³ cells/well) were seeded in 96-well plates and treated with Fluocinolone Acetonide (10⁻¹¹ to 10⁻⁷ M) for 72 hours; MTT reagent was added, and absorbance was measured at 570 nm to assess proliferation.
- For mineralization assay: Cells (5×10⁴ cells/well) were seeded in 6-well plates, treated with Fluocinolone Acetonide + mineralization medium (α-MEM + 50 μg/mL ascorbic acid + 10 mM β-glycerophosphate) for 14 days. ALP activity was measured via p-nitrophenyl phosphate assay, and mineralized nodules were stained with Alizarin Red S (absorbance at 405 nm) [2]
3. DRG Neuron Assay ([3]):
- Primary DRG neurons were isolated from 1-day-old Sprague-Dawley rats, cultured in neurobasal medium with B27 supplement. Neurons (1×10⁵ cells/well) were pretreated with Fluocinolone Acetonide (10⁻⁸ M) for 1 hour, then co-treated with 100 nM paclitaxel for 24 hours. Apoptosis was detected via TUNEL staining (fluorescence microscopy), and TRPV1 protein expression was measured via Western blot (primary antibody against TRPV1, secondary HRP-conjugated antibody) [3]
4. Trabecular Meshwork Cell Assay ([4][6]):
- Primary human trabecular meshwork cells were cultured in DMEM/F12 with 10% FBS. Cells (1×10⁶ cells/well) were treated with Fluocinolone Acetonide (10 nM) for 24 hours. Total RNA was extracted for microarray analysis to identify regulated genes; selected genes (TGF-β1, MMP-9) were validated via real-time PCR. For reporter gene assay, cells were transfected with GRE-luciferase plasmid before drug treatment [4][6]

Animal/Disease Models: PTX-induced peripheral neuropathy model [3]
Doses: 500 μg/kg
Route of Administration: intraperitoneal (ip)injection
Experimental Results: Prevented a marked reduction in intraepidermal nerve fibers density in the plantar surface of the hind paws.

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Murine Paclitaxel-Induced Peripheral Neuropathy Protocol ([3]):
1. Model Induction: Female C57BL/6 mice (8–10 weeks old) were injected intraperitoneally with paclitaxel (20 mg/kg) on days 1, 4, 7, 10 to induce peripheral neuropathy.
2. Drug Administration: Fluocinolone Acetonide was dissolved in 0.9% saline containing 0.1% DMSO. Treatment group mice received intraperitoneal injections of 0.1 mg/kg Fluocinolone Acetonide on days 1, 4, 7, 10 (concurrent with paclitaxel). Control group received 0.9% saline + 0.1% DMSO.
3. Efficacy Detection:
- Mechanical sensitivity: Measured via von Frey filaments (0.008–4 g) on days 0, 7, 14, 21.
- Thermal sensitivity: Measured via hot plate test (52°C) on the same days.
4. Tissue Collection: On day 21, mice were euthanized; dorsal root ganglia (DRG) and sciatic nerves were collected for TUNEL staining and immunohistochemistry (TRPV1 antibody) [3]

Absorption, Distribution and Excretion
Fluocinolone acetone, when used as an intraocular implant, provides sustained release for up to 12 months. Concentrations of fluocinolone acetone are typically high in the vitreous humor and retina, with a small amount dispersed into the aqueous humor. Transdermal absorption of fluocinolone acetone has been reported with varying degrees of absorption depending on the excipients, the integrity of the epidermal barrier, and the use of occlusive dressings. Systemic absorption of fluocinolone acetone is less than 0.1 ng/ml regardless of the route of administration, indicating minimal systemic distribution and primarily local action. Fluocinolone acetone is primarily excreted via the kidneys. It should be noted that the systemic absorbed dose is very low. Due to the extremely low systemic absorption of fluocinolone and the urine concentration being below the limit of quantitation, this pharmacokinetic parameter is not significant. Introducing 1,2 double bonds or fluorine atoms into the molecule significantly slows the metabolism of corticosteroids and correspondingly prolongs their half-life. /Corticosteroids/
¹⁴C is rapidly and primarily excreted via feces (90%), bile (70%), and urine (8%) within 48 hours. More than 7% of (14)C was absorbed after application of a cream containing [(14)C]fluocinolone acetonide to the skin of mice.
...Within 1 hour of subcutaneous injection of [(14)C]fluocinolone acetonide in mice, the concentrations were higher in the liver and injection site, and lower in the pancreas, kidneys, salivary glands, myocardium, pituitary gland, and lacrimal glands. Except for the liver and intestines, tissue (14) concentrations decreased considerably within 24 hours due to bile secretion...
The optimal time for topical fluocinolone acetonide to penetrate the human abdominal skin is when the drug concentration is highest, while maintaining a good partition coefficient between the skin barrier and the excipient.
For more complete data on the absorption, distribution, and excretion of fluocinolone acetonide (6 types), please visit the HSDB records page.

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Metabolism/Metabolites
After absorption, fluocinolone acetonide is primarily metabolized in the liver. It is worth noting that the systemic absorption dose is very low.
...Cortisol and its homologues and synthetic derivatives are generally considered to have similar metabolic properties. ...Metabolism mainly occurs via A-ring reduction, C20 ketone reduction, and side-chain cleavage. Metabolites are excreted as glucuronides, sulfates, and unconjugated compounds. Corticosteroids

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Biological Half-Life
The half-life of fluocinolone acetonide has been reported to be 1.3–1.7 hours.

Protein Binding
Due to very low systemic absorption of fluocinolone acetonide, this pharmacokinetic parameter is not relevant. Interactions Topical application of vitamin A has been reported to reverse corticosteroid-induced impaired wound healing. /Corticosteroids/

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1. In vitro cytotoxicity:
- Fluocinolone acetonide (10⁻⁹ to 10⁻⁶ M) showed no cytotoxicity to THP-1-derived foam cells (cell survival >90% vs. control group, MTT assay)[1]
- In primary dental pulp cells, 10⁻¹¹ to 10⁻⁷ M fluocinolone acetonide did not reduce cell survival (survival >95% vs. control group)[2]
- 10⁻⁸ M fluocinolone acetonide showed no toxicity to primary dorsal root ganglion (DRG) neurons (neuronal survival >90% vs. control group)[3]
2. In vivo toxicity:
- In a mouse neuropathy model, intraperitoneal injection of 0.1 Compared with the control group, mg/kg fluocinolone acetonide (for 2 weeks) did not cause significant changes in body weight, liver function (ALT, AST) or kidney function (BUN, creatinine) [3]
3. Local toxicity (cited from [5]):
- Topical application of fluocinolone acetonide may cause mild local side effects, including skin atrophy (10-15% of users), hypopigmentation (5-8%) and pruritus (3-5%) [5]

[1]. The potential of fluocinolone acetonide to mitigate inflammation and lipid accumulation in 2D and 3D foam cell cultures . BioMed Research International, 2018, 2018.

[2]. Fluocinolone acetonide promotes the proliferation and mineralization of dental pulp cells . Journal of endodontics, 2013, 39(2): 217-222.

[3]. Identification of fluocinolone acetonide to prevent paclitaxel‐induced peripheral neuropathy . Journal of the Peripheral Nervous System, 2016, 21(3): 128-133.

[4]. Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells . BMC medical genomics, 2009, 2(1): 1-14.

[5]. http://en.wikipedia.org/wiki/Fluocinolone_acetonide.

[6]. Glucocorticoids with different chemical structures but similar glucocorticoid receptor potency regulate subsets of common and unique genes in human trabecular meshwork cells. BMC Med Genomics, 2009. 2: p. 58.

Therapeutic Uses
Synthetic glucocorticoids; Topical glucocorticoids. Aside from replacement therapy, the use of corticosteroids and their homologues in disease is empirical. …For any disease, for any patient, the appropriate dose to achieve the desired therapeutic effect must be determined through repeated trials and must be reassessed from time to time as the stage and activity of the disease change… /Corticosteroids/ Glucocorticoids have potent anti-inflammatory and metabolic effects, while the effects of mineralocorticoids are negligible. It is commonly used topically to treat various skin diseases. For the treatment of refractory nummular dermatitis, psoriasis, or chronic neurodermatitis, it is usually used in conjunction with occlusive dressings. For more complete data on the therapeutic uses of fluocinolone acetonide compounds (7 in total), please visit the HSDB record page.

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Drug Warnings
...With corticosteroid treatment lasting for months at doses exceeding the equivalent dose of alternative therapy, the incidence of disabling and potentially fatal side effects increases; except in cases of adrenal insufficiency, administration...is neither a treatment of the underlying cause nor a cure, but merely palliative...anti-inflammatory.../corticosteroids/
Even with application of corticosteroid-containing creams to almost the entire body, there is little evidence of systemic side effects. Topical use of fluocinolone acetonide is contraindicated in tuberculosis, fungal infections, and most viral skin lesions (vaccinia, chickenpox, herpes simplex, etc.).
...Caution should be exercised when using fluoride preparations on the face or other important cosmetic areas, as prolonged use may result in paradoxical rashes.
Veterinary drugs: Propylene glycol solutions typically produce an irritation far exceeding the "transient stinging sensation" described by the manufacturer, and should be avoided especially on broken or exposed skin areas.
For more drug warnings (full list), please refer to the HSDB record page for fluocinolone acetonide (7 types).

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Pharmacodynamics
Fluocinolone is a synthetic anti-inflammatory corticosteroid that interacts with the body to produce vasoconstriction, inhibition of cell membrane permeability, inhibition of mitotic activity, inhibition of immune response, and inhibition of the release of inflammatory mediators. In ophthalmic indications, fluocinolone is administered in the form of an intravitreal microimplant. Clinical trials have shown that even six months after the first dose, the formulation still reduces the recurrence rate of uveitis by 2-fold compared to untreated patients. In addition, intraocular pressure appears to increase slightly after fluocinolone implantation, but monitoring intraocular pressure is crucial.

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1. Drug Background ([5]):
- Fluocinolone acetone is a synthetic, highly potent glucocorticoid with anti-inflammatory, antipruritic, and immunosuppressive effects. Its potency is stronger than that of hydrocortisone (approximately 40-60 times) and prednisolone (approximately 10-20 times) [5]
2. Indications ([5]):
- Approved for the topical treatment of inflammatory skin diseases (e.g., atopic dermatitis, psoriasis, eczema) and ocular inflammation (e.g., uveitis). Off-label use includes pulpitis and peripheral neuropathy [2][3][5]
3. Mechanism of action ([1][2][3][4][6]):
- Fluocinolone acetonide works by binding to the glucocorticoid receptor (GR), forming a GR-drug complex that translocates to the nucleus and regulates the transcription of target genes (e.g., downregulating pro-inflammatory cytokines and upregulating anti-inflammatory proteins). It also inhibits NF-κB activation and TRPV1 expression in neuropathy models [3][4][6]

C24H30F2O6

452.49

452.201

67-73-2

6215

White to off-white solid powder

1.4±0.1 g/cm3

578.5±50.0 °C at 760 mmHg

267-269 °C(lit.)

303.7±30.1 °C

0.0±3.6 mmHg at 25°C

1.577

2.24

2

8

2

32

960

9

C[C@]12C[C@@H]([C@]3([C@H]([C@@H]1C[C@@H]4[C@]2(OC(O4)(C)C)C(=O)CO)C[C@@H](C5=CC(=O)C=C[C@@]53C)F)F)O

FEBLZLNTKCEFIT-VSXGLTOVSA-N

InChI=1S/C24H30F2O6/c1-20(2)31-19-9-13-14-8-16(25)15-7-12(28)5-6-21(15,3)23(14,26)17(29)10-22(13,4)24(19,32-20)18(30)11-27/h5-7,13-14,16-17,19,27,29H,8-11H2,1-4H3/t13-,14-,16-,17-,19+,21-,22-,23-,24+/m0/s1

(1S,2S,4R,8S,9S,11S,12R,13S,19S)-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-6,6,9,13-tetramethyl-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (4.60 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (4.60 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (4.60 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)