Intranasal delivery of peptide drugs offers a non-invasive route with advantages such as avoiding gastric degradation and first-pass metabolism. Several peptide nasal sprays are approved, including calcitonin salmon Miacalcin , desmopressin Stimate, Octostim, Minirin, DDAVP , buserelin Suprefact ,…
Intranasal delivery has gained significant attention as a potential non-invasive route for peptide drugs to enter systemic circulation. The nasal cavity offers several structural advantages for drug absorption. It has a relatively large absorbable surface area, high tissue permeability, and rich vascularization. Additionally, this route avoids enzymatic degradation in the gastrointestinal tract and bypasses hepatic first-pass metabolism, which are common obstacles for oral peptide administration.
These features make the nasal route an attractive alternative to injections for delivering therapeutic peptides. The ability to achieve systemic absorption without needles can improve patient comfort and treatment adherence. Researchers have been exploring this route for decades, and several peptide nasal spray products have already reached the market.
Miacalcin nasal spray contains salmon calcitonin as its active ingredient. Salmon calcitonin is a peptide hormone found in salmon that is similar to human calcitonin. In humans, calcitonin is secreted by the parafollicular cells of the thyroid gland in response to hypercalcemia. It works by reducing blood calcium and phosphorus levels through promoting renal excretion.
Miacalcin is indicated for the treatment of osteoporosis in women who have been menopausal for at least five years. The product should be used together with adequate calcium and vitamin D intake. It is specifically aimed at patients who are not candidates for alternative osteoporosis therapies. This includes individuals for whom other treatments are unsuitable, as well as those who are intolerant or unwilling to use other available therapies.
Desmopressin, a synthetic analog of the natural hormone arginine vasopressin, is available in multiple nasal spray formulations under different trade names. Each formulation has specific indications and dosing characteristics.
Stimate is indicated for patients with hemophilia who have coagulation factor VIII activity levels greater than five percent, classified as mild hemophilia. The active substance is desmopressin acetate. A single spray delivers 0.1 mL containing 150 micrograms of the drug. This dose has an anti-diuretic activity of approximately 600 international units.
The half-life of Stimate nasal spray ranges from 3.3 to 3.5 hours. Intranasal doses can vary from 150 to 450 micrograms. Plasma concentration reaches its maximum approximately 40 to 45 minutes after administration. When given as a 1.5 mg/mL solution via the intranasal route, the bioavailability of Stimate ranges from 3.3 percent to 4.1 percent.
Octostim was originally developed by Ferring Pharmaceuticals as a different nasal spray formulation of desmopressin. It acts as an anti-diuretic agent. Octostim is used to treat central diabetes insipidus, a condition where the kidneys cannot retain water due to a deficiency of antidiuretic hormone ADH . This leads to frequent urination and excessive thirst.
The product is also indicated for temporary thirst and increased urination that may occur after a head injury or certain types of brain surgery. In these uses, desmopressin nasal solution works by helping to reduce the amount of urine produced by the kidneys.
Minirin nasal spray is indicated for the management of primary nocturnal enuresis. It can be used alone or as an adjunct to other non-pharmacological interventions for behavioral modification. Studies have shown it to be effective in certain cases that are difficult to treat with conventional therapy.
Minirin is also indicated for the treatment of central intracranial diabetes insipidus and for anti-diuretic replacement therapy for temporary polyuria following head trauma or surgery in the pituitary region. It is not effective for treating nephrogenic diabetes insipidus. The Minirin nasal spray compression pump delivers 0.1 mL containing 10 micrograms of desmopressin acetate per spray. In addition to the nasal spray, Minirin is also available as an oral tablet.
DDAVP contains desmopressin acetate as the active substance with an anti-diuretic effect. One milliliter 0.1 mg of intranasal DDAVP provides approximately 400 international units of activity. The biphasic half-lives of intranasal DDAVP are 7.8 minutes for the fast phase and 75.5 minutes for the slow phase. In comparison, the other form of lysine vasopressin has fast and slow phase half-lives of 2.5 minutes and 14.5 minutes respectively. Therefore, intranasal DDAVP produces a rapid antidiuretic effect along with a long duration of action after each dose.
Buserelin is used in men to treat advanced prostate cancer. It is not a cure for the disease. Most types of prostate cancer require the male hormone testosterone to grow and spread. Buserelin works by reducing the amount of testosterone produced by the body. This action helps slow or stop the growth of cancer cells and helps relieve symptoms such as painful or difficult urination.
Buserelin is also used to treat endometriosis in women. It works by reducing the body's production of the female hormone estrogen. This effect helps shrink abnormal tissue and reduce symptoms of endometriosis, including pelvic pain and dysmenorrhea.
Buserelin is an artificial hormone similar to the natural hormone gonadotropin-releasing hormone GnRH produced by the human body. Initially, buserelin promotes the secretion of luteinizing hormone LH and follicle-stimulating hormone FSH as an agonist. However, with prolonged administration, the GnRH receptor becomes desensitized and stops responding entirely to buserelin and endogenous GnRH. This profound desensitization leads to a reduction in LH and FSH secretion from the anterior pituitary gland. This is followed by a cessation of gonadal sex hormone production, a significant reduction or loss of spermatogenesis in men, and an absence of ovulation in women. The goal of this process is to starve cancer cells.
Suprefact contains 1.06 mg of buserelin acetate per mL of intranasal aqueous solution, which is equivalent to 1 mg of buserelin free base. For prostate cancer, the usual starting dose is 500 micrograms of buserelin given by subcutaneous injection every eight hours for seven days. This is followed by maintenance therapy with a single daily injection of 200 micrograms of buserelin or 400 micrograms of nasal spray delivered three times daily, with two sprays in each nostril. Women treated with buserelin for endometriosis usually receive buserelin nasal solution at a dose of 400 micrograms, which is two sprays per nostril, three times a day. Treatment typically lasts for six months but should not last longer than nine months.
Like buserelin, nafarelin is a GnRH analog agonist. It is used to treat endometriosis and precocious puberty. It is also used to treat uterine fibroids, to control ovarian stimulation in in vitro fertilization IVF , and as part of cross-sex hormone therapy.
Synarel is indicated for the treatment of central precocious puberty CPP , also called gonadotropin-dependent precocious puberty, in both male and female children. It is administered as a nasal spray two to three times a day. Synarel nasal solution contains nafarelin acetate at a concentration of 2 mg/mL. After filling the pump, each actuation delivers a spray of approximately 100 microliters containing approximately 200 micrograms of nafarelin free base. The contents of a spray bottle are provided to deliver at least 60 sprays.
After intranasal administration, nafarelin acetate is rapidly absorbed into the systemic circulation. Maximum serum concentrations are reached between 10 and 40 minutes. After a single dose of 200 micrograms of free base nafarelin, the average peak concentration is 0.6 ng/mL, with a range of 0.2 to 1.4 ng/mL. After a single dose of 400 micrograms of free base nafarelin, the mean peak concentration observed is 1.8 ng/mL, with a range of 0.5 to 5.3 ng/mL. The bioavailability of the 400 microgram dose averages 2.8 percent, ranging from 1.2 to 5.6 percent. The mean serum half-life of nafarelin after intranasal administration is approximately three hours. About 80 percent of nafarelin acetate is bound to plasma proteins at four degrees Celsius.
Oxytocin nasal spray has a range of uses, from treating anxiety disorders to autism. In clinical trials, oxytocin has shown promise in the treatment of obesity and may have other super-indicated uses. Oxytocin is a naturally occurring hormone that can also be used as a supplement.
Semax peptides are known for their neuroprotective, educational, and neurorestorative properties. Traditionally, Semax has been used to treat depression and anxiety. Semax was originally developed based on the molecular structure of ACTH adrenocorticotropic hormone . Ongoing research suggests that Semax may be useful for individuals with cognitive disorders, including dementia, stroke, and ADHD. It may also improve mental clarity and concentration, reduce anxiety and depressive symptoms, improve clarity of thought and focus, and reduce the effects of stress. For these reasons, Semax is given the free translation of brain peptide in Chinese. Semax is used for a wide range of indications in medical settings. It has been prescribed for the treatment of anxiety disorders, ischemic events, stroke, neuroregeneration, ADHD, opioid withdrawal, Parkinson's disease, Alzheimer's disease, thrombosis, and gastric disorders. It is worth noting that Cerebrolysin, another neuropeptide, is mainly used in countries such as Russia and Ukraine and is not approved in most countries around the world.
Most biological drugs are readily degraded enzymatically in the gastrointestinal tract, which is why the most common route of administration is by injection. However, when drugs are administered via the intranasal route, they enter through the respiratory zone around the inferior turbinate. The nasal mucosa in this region is richly vascularized and lined with columnar epithelial cells that provide a large surface area of over 150 square centimeters. This structure is conducive to drug absorption and has strong permeability. Because the intranasal route avoids enzymatic degradation in the gastrointestinal tract and first-pass metabolism in the liver, it reduces the common barriers that limit drug absorption and facilitates a rapid onset of action.
Intranasal delivery leads to higher patient compliance compared to injections. This route is non-invasive and highly tolerable, which expands the possibilities for patient self-administration. Good patient compliance is important for therapeutic outcomes, especially for intranasal drug products that must be administered regularly and consistently to ensure sustained therapeutic effects. Patient satisfaction and comfort with the administration method depend heavily on their compliance.
In summary, intranasal peptide delivery offers a viable non-invasive alternative with multiple approved products already on the market. The advantages of bypassing first-pass metabolism, enabling nose-to-brain delivery, and improving patient compliance continue to drive research and development in this field.
Peptides referenced: Semax, Gonadorelin, Cerebrolysin, Calcitonin (Salmon), Oxytocin, Vasopressin, Desmopressin, Nafarelin.
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