Polyoxyl 60 hydrogenated castor oil free nanosomal formulation of immunosuppressant Tacrolimus: pharmacokinetics, safety, and tolerability in rodents and humans.
OBJECTIVE
Develop Nanosomal formulation of Tacrolimus to provide safer alternative treatment for organ transplantation patients. Investigate safety, tolerability and pharmacokinetics of Nanosomal Tacrolimus formulation versus marketed Tacrolimus containing polyoxyl 60 hydrogenated castor oil (HCO-60) that causes side effects.


METHODS
Nanosomal Tacrolimus was prepared in an aqueous system. The particle size was measured by Particle Sizing Systems and structure morphology was determined by freeze-fracture electron microscopy. Investigational safety studies were conducted in mice and rats. Safety and pharmacokinetics of Nanosomal Tacrolimus were also evaluated in healthy human subjects.


RESULTS
The morphology of Nanosomal Tacrolimus showed a homogeneous population of nanosized particles with mean particle size of less than 100 nm. A 14 day consecutive administration of Nanosomal Tacrolimus up to 5 and 10mg/kg dose in rats and mice respectively, resulted in no mortality. Nanosomal Tacrolimus in human studies showed that it is safe and the pharmacokinetics profile is similar to the marketed HCO-60 based Tacrolimus. No significant change in peripheral blood lymphocyte percentage was noted in either mice or healthy human male subjects.


CONCLUSIONS
Nanosomal Tacrolimus is well characterized product which provides a new treatment option. It contains no alcohol or surfactants like HCO-60. Thus, Nanosomal Tacrolimus presents a new and improved therapeutic approach for organ transplant patients compared to the marketed HCO-60 based Tacrolimus product.
Ali
Shoukath M
SM
Jina Pharmaceuticals Inc., Libertyville, IL 60048, USA.
Ahmad
Ateeq
A
Sheikh
Saifuddin
S
Ahmad
Moghis U
MU
Rane
Rajendar C
RC
Kale
Prashant
P
Paithankar
Mahesh
M
Saptarishi
Dipak
D
Sehgal
Ashish
A
Maheshwari
Kirti
K
Ahmad
Imran
I
D000293:Adolescent; D000328:Adult; D000818:Animals; D019540:Area Under Curve; D002368:Castor Oil / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D005079:Excipients; D005260:Female; D005614:Freeze Fracturing; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D007202:Indicators and Reagents; D018655:Lymphocyte Count; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D053758:Nanoparticles; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
D005079:Excipients; D007166:Immunosuppressive Agents; D007202:Indicators and Reagents; C023040:polyethoxylated castor oil; D002368:Castor Oil; D016559:Tacrolimus