Novel Milrinone Nanoformulation for Use in Cardiovascular Diseases: Preparation and in Vitro Characterization.
Nikita LomisFrancis GaudreaultMeenakshi MalhotraSusan WestfallDominique Shum-TimSatya PrakashPublished in: Molecular pharmaceutics (2018)
Cardiovascular diseases are the leading causes of mortality across the globe. Over the years, various drug formulations and delivery methods have been tested for cardiac repair. Milrinone (MRN) is a widely known cardiac inotrope drug used for the treatment of congestive heart failure in patients, however, its efficacy is limited. This study is the first to report the design of a novel MRN-nanoformulation using human serum albumin nanoparticles (HSA-NPs). The HSA-NPs exhibit promising drug delivery characteristics, such as target specificity, nonimmunogenicity, biocompatibility, and enhanced bioavailability. This article describes a MRN-nanoformulation design for in vitro drug release, cellular uptake, biocompatibility, and other features. The MRN-nanoformulation was prepared by the ethanol desolvation technique and key parameters were optimized to obtain a desired particle size of 154.2 ± 5.8 nm, zeta potential of -29.5 ± 2.9 mV, and a drug encapsulation efficiency of 41.1 ± 1.7%. Molecular docking studies have revealed that MRN binds in the hydrophobic cavity of HSA, which has also been indicated by circular dichroism and enzyme-mediated drug release studies in the presence of trypsin, pepsin, proteinase K, protease, and cathepsin D. The intracellular uptake of fluorescently tagged MRN-HSA-NPs using HUVEC and H9c2 cells was evaluated by flow cytometry. The nanoparticle toxicity results indicated that MRN-HSA-NPs show significantly lower cytotoxicity and higher cell viability ( P < 0.0001) as compared to the MRN-lactate drug in HUVEC (61.6 ± 3.7% vs 36.2 ± 2.9%) and H9c2 (58.8 ± 5.7% vs 18.8 ± 4.9%) cells. These studies indicate that the novel MRN-nanoformulation offers better drug delivery procedures than currently used methods and has potential in treatment of congestive heart failure and other cardiovascular diseases.
Keyphrases
- drug release
- drug delivery
- heart failure
- cardiovascular disease
- molecular docking
- induced apoptosis
- left ventricular
- flow cytometry
- end stage renal disease
- cancer therapy
- cell cycle arrest
- adverse drug
- human serum albumin
- case control
- emergency department
- ejection fraction
- drug induced
- cell death
- type diabetes
- prognostic factors
- peritoneal dialysis
- human health
- oxide nanoparticles
- signaling pathway
- oxidative stress
- risk factors
- combination therapy
- ionic liquid
- patient reported outcomes