Antibiotic; DNA alkylator

Streptozotocin is frequently used to induce diabetes mellitus in experimental animals. The low-affinity GLUT 2 glucose transporter allows streptozotocin to accumulate in pancreatic beta cells in a selective manner. A 4-month injection of streptozotocin (60 mg/kg) causes cataract development, a rapid degranulation of beta cells without necrosis, and an accumulation of glycogen in the kidney's proximal convoluted tubules. Rats with “Streptozotocin diabetes” exhibit persistent small, possibly secretory granules in the Golgi zone of beta cells, and lesions in the pancreatic exocrine cells at 100 mg/kg.[3]
Streptozotocin has been shown to cause cancer in rats, mice and hamster. In hamsters, a solitary dose of streptozotocin can cause tumors in the kidney, liver, pancreas, uterus, and liver. Normotensive Wistar Kyoto rats (WKY) given intraperitoneal injections of streptozotocin (100–150 mg/kg) for a year cause carcinogenesis, with tumor incidence in the liver being 70%, the kidneys 20%, and the liver and kidneys 10%.[4]

---

We studied the oncogenic action of neonatal streptozotocin (STZ) treatment in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) for 12 months. Two-day-old male neonates were intraperitoneally injected with STZ of which doses were 37.5-75.0 mg/kg for SHR and 100.0-150.0 mg/kg for WKY. The 12-month survival rate was 16 of 22 (73%) in SHR and 10 of 14 (71%) in WKY, respectively. The incidence of tumors in STZ-treated SHR was 27% in liver, 14% in kidney and 5% in liver and kidney, being related to the dose of STZ given, namely, 25% in 37.5 mg/kg, 50% in 50.0 or 62.5 mg/kg and 75% in 75.0 mg/kg. In STZ-treated WKY which survived 12 months, all had tumors, namely, 70% in liver, 20% in kidney and 10% in liver and kidney. Histological features of liver and kidney tumors were characteristic of hepatoma and nephroblastoma, respectively. Islet cell tumor was evident in 4 of 10 (40%) in SHR treated with lower doses of STZ (less than or equal to 50 mg/kg) but not in SHR and WKY treated with higher doses (62.5-150.0 mg/kg). The present study indicates that neonatal STZ treatment has the oncogenic action on liver, kidney and pancreatic islet. [4]

---

Diabetes is induced in mice by using streptozotocin (STZ), a compound that has a preferential toxicity toward pancreatic β cells. We evaluated nude male mice from various sources for their sensitivity to a single high dose (160 to 240 mg/kg) of STZ. Diabetes was induced in male mice (age: median, 12 wk; interquartile range, 11 to 14 wk; body weight, about 30 g) from Taconic Farms (TAC), Jackson Laboratories (JAX), and Charles River Laboratories (CRL). Mice were monitored for 30 d for adverse side effects, blood glucose, and insulin requirements. In CRL mice given 240 mg/kg STZ, more than 95% developed diabetes within 4 to 5 d, and loss of body weight was relatively low (mean, 0.4 g). In comparison, both TAC and JAX mice were more sensitive to STZ, as evidenced by faster development of diabetes (even at a lower STZ dose), greater need for insulin after STZ, greater body weight loss (mean: TAC, 3.5 g; JAX, 3.7 g), and greater mortality. We recommend conducting exploratory safety assessments when selecting a nude mouse source, with the aim of limiting morbidity and mortality to less than 10%. [5]

The use of Western blot analysis is of great importance in research, and the measurement of housekeeping proteins is commonly used for loading controls. However, Ponceau S staining has been shown to be an alternative to analysis of housekeeping protein levels as loading controls in some conditions. In the current study, housekeeping protein levels were measured in skeletal muscle hypertrophy and  Streptozotocin -induced diabetes experimental models. The following housekeeping proteins were investigated: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β-actin, α-tubulin, γ-tubulin, and α-actinin. Evidence is presented that Ponceau S is more reliable than housekeeping protein levels for specific protein quantifications in Western blot analysis. [6]

---

Streptozocin is an effective agent that methylates DNA; in HL60, K562, and C1498 cells, it has IC50 values of 11.7, 904, and 1024 μg/mL, respectively.

In 96-well plates, human and murine cell lines are cultivated in triplicate at a density of 2×10⁴ cells/well, either in the absence (untreated control) or in the presence of different concentrations of ALX (20-3000 μg/mL) or STZ (1-3000 μg/mL) for 48 hours at 37°C in a humidified atmosphere with 5% CO₂. The experiments used cells cultured in complete medium as a control, and cells cultured in dH₂O at a final concentration of 0.1% as a control for solvent toxicity. The MTT assay is used in accordance with the manufacturer's instructions to determine the effects of the tested drugs on the growth or viability of tumor cells. GraphPad Prism 4 is used to calculate the IC50 values, or drug concentrations that cause a 50% inhibition of cell growth.

---

The ability of beta cells to endure assaults by various environmental agents, including toxins and viruses, may be relevant to the development of diabetes. Researchers have examined the mode of cell death caused by  Streptozotocin (STZ) in a murine pancreatic beta cell line, INS-1. Apoptosis was identified by detection of initial endonuclease-mediated DNA strand breaks by DNA gel electrophoresis. Apoptosis and necrosis were distinguished morphologically by light and electron microscopy. Higher rates of apoptosis, as compared to necrosis, were observed when cells were exposed to 15 mM STZ for 1 hr followed by a 24 hrs recovery period. Higher doses of STZ (30 mM) caused the cells to undergo necrosis (22%) as well as apoptosis (17%). These results suggest that the cytotoxic effect of STZ, at low doses, on beta cells involves the activation of the apoptotic pathway, whereas, at high doses, the mode of beta cell death is predominantly necrosis.

Streptozotocin (STZ) for Diabetes Model Induction
1. General Properties of STZ
• Applications: Suitable for establishing both Type 1 and Type 2 diabetes models
• Pharmacokinetics:
• Highly water-soluble with widespread tissue distribution
• Capable of crossing blood-brain and placental barriers
• Hepatic bioactivation leads to DNA methylation and pancreatic β-cell damage
• Species- and administration-dependent elimination half-life

2. Type 1 Diabetes Induction Protocol[3][4][5]
Mechanism
Direct cytotoxic effects on pancreatic β-cells

Modeling Parameters
Species Strain/Sex/Age Administration Dosage Regimen
Mouse C57BL/6 ♀ 10wk IP injection 200 mg/kg single dose
Rat SD/Wistar ♂ 8-10wk IP injection 65 mg/kg single dose

Critical Notes
1. Species sensitivity:
• Male rats preferred (greater STZ susceptibility)
• Strain variation: DBA/2 > C57BL6 > Balb/cJ (resistant to MLD-STZ)[4]

2. Pre-treatment:
• Fasting (water allowed) enhances β-cell sensitivity

• Rapid IV injection recommended
3. Mortality management:
• Provide 10% sucrose water post-injection
• For >20% mortality: 5% glucose solution IP within 6h[5]

4. Mandatory pilot studies required (literature doses not directly applicable)
Success Criteria
• Primary endpoint: Blood glucose >300 mg/dL (16.7 mmol/L)
• Secondary markers:
• Polydipsia/polyuria
• Weight loss
• Elevated serum biomarkers (TC, AST, TG, LDL)

3. Type 2 Diabetes Induction Protocol[3][4][5]
Mechanism
Combined β-cell dysfunction and insulin resistance (high-fat diet + subtoxic STZ)

Modeling Parameters
Species Strain/Sex/Age Administration Dosage Regimen
Mouse C57BL/6 ♀ 10wk IP + HFD 40 mg/kg × 4 days
Rat SD/Wistar ♂ 8-10wk IP + HFD 25 mg/kg × 5 days

Validation Criteria
(Identical to Type 1 diabetes model)

Key Advantages
• Established protocol with high reproducibility
• Mimics human disease pathophysiology
• Cost-effective compared to genetic models

Technical Considerations
• STZ stability: Prepare fresh solution in citrate buffer (pH 4.5)
• Monitoring: Daily glucose checks for 2 weeks post-induction
• Housing: Maintain at 22±2°C with 12h light/dark cycle

---

Mice: The mice used are male C57BL/6 (10–16 weeks).The age distribution of the mice treated with Streptozocin and ALX, along with the controls, is as follows: n = 7 for Streptozocin xenograft, n = 11 for ALX xenograft, n = 7 for Streptozocin non-transplanted, n = 15 for ALX non-transplanted, and n = 7 for Streptozocin non-transplanted.Male C57BL/6 mice are given an inhalation anesthetic injection via the penile vein, consisting of either 180 mg/kg of streptozocin or 75 mg/mL of ALX. Male C57BL/6 mice make up the control group. Before the drug injection, six hours later, and every day after, blood glucose levels and body weight are recorded.

---

Rats: To induce menopause, thirty rats had their ovaries removed. Streptozocin (50 mg/kg) is injected intraperitoneally into rats one week following oophorectomy to cause diabetes mellitus (DM). Three days following the administration of streptozocin, blood glucose levels are measured; values greater than 250 mg/dL are regarded as positive for diabetes.

Absorption, Distribution and Excretion
Poor oral absorption (17-25%)
As much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney.
IN ALL THESE SPECIES /MICE, RATS, CATS, MONKEYS & DOGS/ STR /STREPTOZOTOCIN/ GIVEN PARENTERALLY ... MARKEDLY CONCENTRATED IN LIVER & KIDNEY; FOR EXAMPLE, IN DOGS ... RETAINED IN LIVER FOR MANY HR AFTER ... NO LONGER ... DETECTED IN BLOOD .
STREPTOZOTOCIN ... WELL ABSORBED FROM GI TRACT IN MICE, BUT ABSORPTION WAS POOR IN MONKEYS & NEGLIGIBLE IN DOGS.
(14)C-LABELLED STREPTOZOTOCIN GIVEN BY IV INJECTION WAS RAPIDLY CLEARED FROM BLOOD OF RATS, SO THAT LESS THAN 1% REMAINED AFTER 10 MINUTES.
STREPTOZOTOCIN (NSC-85998) WAS RAPIDLY EXCRETED IN URINE OF TREATED MICE; 72% OF AN INJECTED DOSE IN THE 4-HR URINE. FIVE URINARY METABOLITES WERE DETECTED ... .
Following intraperitoneal or IV administration of streptozocin in animals, the drug and its metabolites are rapidly distributed mainly into the liver, kidneys, intestine, and pancreas, with lower concentrations being distributed into skeletal muscle, spleen, lungs, heart, and thymus. Concentrations of the drug or its metabolites in the liver, kidneys, intestine, and pancreas are consistently higher than those in plasma. Streptozocin does not appear to cross the blood-brain barrier in animals or humans; however, in humans, metabolites of streptozocin readily distribute into CSF. ... The drug readily crosses the placenta in monkeys.

---

Metabolism / Metabolites
Primarily hepatic
STUDIES WITH STREPTOZOTOCIN LABELLED WITH (14)C IN DIFFERENT POSITIONS INDICATE THAT ITS RAPID METABOLISM IN RAT ... RESULTS IN METABOLITE DERIVED FROM METHYL BEARING NITROSOUREIDO SIDECHAIN. /SRP: DIAZOMETHANE/
/IN MICE URINE/ FIVE URINARY METABOLITES WERE DETECTED; 2 OF THEM WERE THE ALPHA AND BETA-ANOMERS OF THE ANTIBIOTIC.
Streptozocin and metabolites have a short distribution phase (t1/2 6 min) followed by possibly two elimination phases representing active metabolites (t1/2 beta 3.5 hr, t1/2 gamma 40 hr).
Streptozocin is not orally active. After intravenous administration, it is rapidly cleared from plasma and is undetectable after three hours. Metabolites are detected in plasma for up to 24 hours. The drug concentrates in certain tissues; the liver and kidneys contain the highest levels, and pancreas also concentrates streptozocin. Parent drug and metabolites are eliminated rapidly by the kidney; 60% to 70% of a dose is recovered in urine within four hours. Only 10% to 20% of an excreted dose is parent drug.
Primarily hepatic
Route of Elimination: As much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney.
Half Life: 5-15 minutes

---

Biological Half-Life
5-15 minutes
AFTER IV INFUSIONS OF 200-1600 MG/SQ M, PEAK CONCN IN PLASMA ARE 30-40 UG/ML; HALF-LIFE OF DRUG IS APPROX 15 MIN. ONLY 10-20% OF DOSE IS RECOVERED IN URINE.
... STREPTOZOTOCIN ... FOLLOW APPARENT TWO-COMPARTMENT MODEL KINETICS IN MAN AFTER BOLUS IV INJECTION, WITH MEAN FAST & SLOW DISPOSITION HALF-TIME VALUES OF 4.6 & 40 MIN RESPECTIVELY. THE LATTER VALUE IS 2.5-FOLD GREATER THAN REPORTED PREVIOUSLY FOR PT RECEIVING STREPTOZOTOCIN BY SLOW IV INFUSION.
SEVEN PATIENTS GIVEN SINGLE 1.5 G/SQ M IV DOSE SHOWED MEAN HALF-LIFE OF APPROX 40 MINUTES & HALF-LIFE OF ELIMINATION OF ABOUT 15 MINUTES.

Toxicity Summary
Streptozotocin is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas. It is used in medical research to produce an animal model for Type 1 diabetes in large dose as well as Type 2 diabetes with multiple low doses. Streptozotocin is similar enough to glucose to be transported into the cell by the glucose transport protein GLUT2, but is not recognized by the other glucose transporters. This explains its relative toxicity to beta cells, since these cells have relatively high levels of GLUT2. Streptozotocin is a glucosamine-nitrosourea (i.e. alkylating) compound. As with other alkylating agents in the nitrosourea class, it is toxic to cells by causing damage to the DNA, though other mechanisms may also contribute.

---

Toxicity Summary
Streptozotocin is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas. It is used in medical research to produce an animal model for Type 1 diabetes in large dose as well as Type 2 diabetes with multiple low doses. Streptozotocin is similar enough to glucose to be transported into the cell by the glucose transport protein GLUT2, but is not recognized by the other glucose transporters. This explains its relative toxicity to beta cells, since these cells have relatively high levels of GLUT2. Streptozotocin is a glucosamine-nitrosourea (i.e. alkylating) compound. As with other alkylating agents in the nitrosourea class, it is toxic to cells by causing damage to the DNA, though other mechanisms may also contribute.

---

Hepatotoxicity
Serum aminotransferase elevations occur in up to two-thirds of patients treated with streptozocin, but the abnormalities are generally mild, transient and not associated with symptoms or jaundice. Hepatotoxicity is more common with daily dosing and high doses of streptozocin, but with higher doses renal and hematologic toxicities usually overshadow hepatic injury. There have been two reports of rapidly progressive and fatal acute liver failure in patients treated with streptozocin. In one instance, no other chemotherapy was given, in another fluorouracil was coadministered and the patient presented with fever, anuria, acute hepatitis [ALT 1280, bilirubin 11.9, prothrombin index 10%, eosinophils 2600/ µL] at the end of a 5 day course of treatment. In contrast, there have been no individual published case reports of self-limited clinically apparent liver injury attributed to streptozocin, but it has had limited use, as pancreatic islet cell carcinoma and neuroendocrine tumors are rare.
Likelihood score: D (possible cause of clinically apparent liver injury).

---

Non-Human Toxicity Values
LD50 Mouse female ip 360 mg/kg
LD50 Mouse female iv 275 mg/kg
LD50 Dog male iv 50 mg/kg

---

Exposure Routes
Intravenous. Poor oral absorption (17-25%).

---

Symptoms
Symptoms of overdose include nausea and vomiting, anorexia, myelosuppression; and nephrotoxicity.

---

Adverse Effects

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.
IARC Carcinogen - Class 3: Chemicals are not classifiable by the International Agency for Research on Cancer.
NTP Carcinogen - Reasonably anticipated to be a human carcinogen.

---

Streptozotocin (Streptozocin, STZ, CAS No. 18883-66-4) is a monofunctional nitrosourea derivative isolated from Streptomyces achromogenes. It has broad spectrum antibiotic activity and antineoplastic properties and is often used to induce diabetes mellitus in experimental animals through its toxic effects on pancreatic beta cells. STZ is a potent alkylating agent known to directly methylate DNA and is highly genotoxic, producing DNA strand breaks, alkali-labile sites, unscheduled DNA synthesis, DNA adducts, chromosomal aberrations, micronuclei, sister chromatid exchanges, and cell death. This antibiotic was found to be mutagenic in bacterial assays and eukaryotic cells. STZ is also carcinogenic; a single administration induces tumors in rat kidney, liver, and pancreas. Several lines of evidence indicate that free radicals are involved in the production of DNA and chromosome damage by this compound. Because of the use of STZ as an antineoplastic agent, the study of its genotoxicity has considerable practical significance. The purpose of this review is to present our current knowledge regarding the genotoxicity of STZ. [1]

---

Interactions
EXPERIMENTALLY ... SHOWN ... THAT DIABETES INDUCED IN RATS BY ... STREPTOZOTOCIN ENHANCES HEPATOTOXICITY OF CARBON TETRACHLORIDE. REVERSAL OF DIABETIC STATE BY INSULIN TREATMENT PREVENTED THE POTENTIATED RESPONSE.
Male Wistar rats were divided into six groups. For inducing diabetes, a single iv injection of 60 mg streptozotocin/kg in a physiological saline solution was given at the time indicated below. Manganese was given by ip injection of 15 mg manganese chloride/kg/day in the saline solution for a period indicated in each group. Group 1 was injected with a vehicle for streptozotocin and saline solution for 2 wk (control group). Group 2 was given streptozotocin and treated with saline for 2 wk (streptozotocin group). Group 3 was given the vehicle for streptozotocin and saline for 1 wk, then received manganese for 2 wk (saline-manganese group). Group 4 was injected with streptozotocin and later treated in the same way as in group 3 (streptozotocin-manganese group). Group 5 was administered with managanese for 2 wk, given streptozotocin and followed by 1 wk saline administration (manganese-streptozotocin-saline group). Group 6 was also given manganese for 2 wk and streptozotocin but followed by manganese for 1 wk (manganese-streptozotocin-manganese group). When streptozotocin was given, the blood glucose level rose over 400 mg/dl and stabilized in a few days. The manganese content in the pancreas, spleen, and kidney of streptozotocin-manganese-treated rats were much lower than those in the tissues in group 3, whereas, those in the brain, thymus, and liver remained unchanged. The pancreas, kidney, and brain of group 6 showed more of an incr in manganese content than did those in the manganese-streptozotocin-saline group (group 5). The liver showed a slight incr in manganese content, but the thymus and spleen of group 6 had less manganese contents than did those of group 5.
In rats, the development of cataracts /by streptozotocin/ were interfered with by administering nicotinamide, a unsaturated fat diet, vitamin E, or aldose- reductase inhibitors.
Concurrent administration of streptozocin with carmustine profoundly enhanced marrow toxicity and the incidence of thrombocytopenia; therapeutic activity was not enhanced.
For more Interactions (Complete) data for STREPTOZOTOCIN (16 total), please visit the HSDB record page.

---

Non-Human Toxicity Values
LD50 Mouse female ip 360 mg/kg
LD50 Mouse female iv 275 mg/kg
LD50 Dog male iv 50 mg/kg

[1]. Mutat Res . 2002 Dec;512(2-3):121-34.

[2]. Biochem Mol Biol Int . 1996 Aug;39(6):1229-36.

[3]. Diabetes . 1967 Jan;16(1):51-6.

[4]. Tohoku J Exp Med . 1989 Oct;159(2):83-90.

[5]. Comp Med . 2011 Aug;61(4):356-60.

[6]. Anal Biochem . 2016 Jul 1:504:38-40.

Therapeutic Uses
Antibiotics, Aminoglycoside; Antibiotics, Antineoplastic
... A SPECIFIC BETA CELL TOXIN & THEREFORE USEFUL IN TREATMENT OF METASTATIC ISLET CELL TUMORS.
IT HAS ... BEEN FOUND TO BE ACTIVE IN HODGKIN'S DISEASE, OTHER LYMPHOMAS, & OCCASIONALLY IN MELANOMA & MALIGNANT CARCINOID TUMORS ... .
THE PROFUSE WATERY DIARRHEA OBSERVED IN PATIENTS WITH PANCREATIC CHOLERA (VERNER MORRISON SYNDROME, SECRETORY DIARRHEA) PRODUCED BY METASTATIC NONBETA CELL TUMORS HAS BEEN RELIEVED BY INFUSION OF STREPTOZOCIN INTO THE HEPATIC ARTERY.
MEDICATION (VET): ... EMPLOYED AS DIABETOGENIC AGENT IN EXPERIMENTAL ANIMALS.

---

Drug Warnings
PATIENTS WITH PRE-EXISTING IMPAIRED RENAL FUNCTION SHOULD NOT RECEIVE STREPTOZOTOCIN.
STREPTOZOTOCIN FREQUENTLY ASSOCIATED WITH CHANGES IN LIVER SCAN. SUGGESTED THAT MINOR SCAN CHANGES MIGHT BE ATTRIBUTED ERRONEOUSLY TO INTRINSIC HEPATIC DISEASE.

---

Pharmacodynamics
Streptozocin is an antitumour antibiotic consisting of a nitrosourea moiety interposed between a methyl group and a glucosamine. Streptozocin is indicated in the treatment of metastatic islet cell carcinoma of the pancreas. Streptozocin inhibits DNA synthesis in bacterial and mammalian cells. In bacterial cells, a specific interaction with cytosine moieties leads to degradation of DNA. The biochemical mechanism leading to mammalian cell death has not been definitely established; streptozocin inhibits cell proliferation at a considerably lower level than that needed to inhibit precursor incorporation into DNA or to inhibit several of the enzymes involved in DNA synthesis. Although streptozocin inhibits the progression of cells into mitosis, no specific phase of the cell cycle is particularly sensitive to its lethal effects.

C8H15N3O7

265.22

265.091

C, 36.23; H, 5.70; N, 15.84; O, 42.23

18883-66-4

29327

White to off-white solid powder

1.9±0.1 g/cm3

121 °C (dec.)(lit.)

1.670

-1.33

5

8

2

18

315

5

O1[C@@]([H])([C@@]([H])([C@]([H])([C@@]([H])([C@@]1([H])C([H])([H])O[H])O[H])O[H])N([H])C(N(C([H])([H])[H])N=O)=O)O[H]

ZSJLQEPLLKMAKR-GKHCUFPYSA-N

InChI=1S/C8H15N3O7/c1-11(10-17)8(16)9-4-6(14)5(13)3(2-12)18-7(4)15/h3-7,12-15H,2H2,1H3,(H,9,16)/t3-,4-,5-,6-,7+/m1/s1

1-methyl-1-nitroso-3-[(2S,3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)oxan-3-yl]urea

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.  (2). This product is not stable in solution, please use freshly prepared working solution for optimal results.

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 (7.84 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.

---

Solubility in Formulation 2: ≥ 2.08 mg/mL (7.84 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.

---

View More

Solubility in Formulation 3: ≥ 2.08 mg/mL (7.84 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.

---

Solubility in Formulation 4: Saline: 30 mg/mL

---

Solubility in Formulation 5: 100 mg/mL (377.05 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

---

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