Albumin Nanoparticles for Delayed Release of Vancomycin

TETTAMANTI, CECILIA S.; AIASSA, VIRGINIA; MARTINEZ, SOFIA M.; ALLEMANDI, DANIEL A.; DANIELA A. QUINTEROS

Rosario

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas. RICiFa.; 2023

RICiFa

At present, the use of nanotechnology for the development of drug carriers systems for localdelivery is being widely studied to improve the efficacy of treatments. In particular, in the case ofantibiotics, the aim is to minimize undesired side-effects caused by antibiotics. One of the mostcommon bacterial agents causing infections is Staphylococcus aureus (SA), which can lead toserious complications. SA is frequently isolated from soft tissues and skin, lower respiratory tractinfections as well as endocarditis and osteomyelitis. The treatment of osteomyelitis remains achallenge for orthopedic surgeons. The most common agent in this type of infection is methicillinresistant SA (MRSA). MRSA is resistant to penicillins and broad-spectrum cephalosporins, andMRSA osteomyelitis is the most difficult way to treat and obtain bacterial eradication. Vancomycin(Van) has been recognized as an effective antibiotic against MRSA. Van must be administered inlarge doses to provide a sufficient level in the bone; this can cause side effects such asnephrotoxicity or ototoxicity and gastrointestinal side effects, and a higher cost. Therefore, thelocal release of Van from a nanometer system is a promising strategy to eliminate infection. Theuse of human serum albumin (HSA) nanoparticles presents numerous advantages, due to thenature of the protein; it is non-toxic, without antigenic activity and is biodegradable.This work presents the preparation of HSA nanoparticles loaded with Van (NpHSA-Van). TheNpHSA-Van were synthesized by the simple method which consists of a desolvation stage withthermal stabilization (at 50°C and 75°C). The characterization of the formulations was performedusing Diffraction Light Scattering (DLS) obtaining an average size of 180 nm, a polydispersity index(PDI) less than 0.2 and a negative Z potential around 40 mV. These results show that NpHSA-Vanhas a homogeneous size and high stability. The amount of drug charged in the nanoparticles wasdetermined by quantifying the Van encapsulated in the nanoparticles by HPLC, the encapsulationefficiency (EE) was 75%. SEM images showed that NpASH-Van have a spherical shape and have ahomogeneous distribution in shape and size. In vitro release profiles were studied in Franz cells,which showed that the system has a slow and controlled release of Van. The physical stability ofthe nanoparticles was evaluated at 30 days of preparation, stored at 4°C. The parameters studieddo not change significantly and therefore these formulations are stable at the time studied. Inaddition, NpHSA-Van were lyophilized, using as cryoprotective agent Sucrose at 3%, and it wasobserved that after rehydration the nanoparticles return to the original state and there are nosignificant modifications in size, PDI, ZP, EE and release profile. The antimicrobial activity of thesystems was evaluated against reference ATCC strains (methicillin-resistant and methicillinsensitive SA) by determining the minimum inhibitory concentration and minimum bactericidalconcentration. In addition, a death curve was performed for MRSA. These studies showed thatvancomycin maintains antimicrobial activity still encapsulated in the nanoparticles.Based on the results obtained, the development of vancomycin-loaded HSA nanoparticles can beconsidered as an effective approach to prolong the release of the drug and improve the efficacy oflocal treatment.