Albumin Nanoparticles for Delayed Release of Vancomycin

Rosario

Otro; 7ma Reunión Internacional de Ciencias Farmacéuticas; 2023

Reunión Internacional de Ciencias Farmacéuticas

At present, the use of nanotechnology for the development of drug carriers systems for local delivery is being widely studied to improve the efficacy of treatments. In particular, in the case of antibiotics, the aim is to minimize undesired side-effects caused by antibiotics. One of the most common bacterial agents causing infections is Staphylococcus aureus (SA), which can lead to serious complications. SA is frequently isolated from soft tissues and skin, lower respiratory tract infections as well as endocarditis and osteomyelitis. The treatment of osteomyelitis remains a challenge for orthopedic surgeons. The most common agent in this type of infection is methicillin-resistant SA (MRSA). MRSA is resistant to penicillins and broad-spectrum cephalosporins, and MRSA 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 in large doses to provide a sufficient level in the bone; this can cause side effects such as nephrotoxicity or ototoxicity and gastrointestinal side effects, and a higher cost. Therefore, the local release of Van from a nanometer system is a promising strategy to eliminate infection. The use of human serum albumin (HSA) nanoparticles presents numerous advantages, due to the nature 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). The NpHSA-Van were synthesized by the simple method which consists of a desolvation stage with thermal stabilization (at 50°C and 75°C). The characterization of the formulations was performed using 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-Van has a homogeneous size and high stability. The amount of drug charged in the nanoparticles was determined by quantifying the Van encapsulated in the nanoparticles by HPLC, the encapsulation efficiency (EE) was 75%. SEM images showed that NpASH-Van have a spherical shape and have a homogeneous 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 of the nanoparticles was evaluated at 30 days of preparation, stored at 4°C. The parameters studied do not change significantly and therefore these formulations are stable at the time studied. In addition, NpHSA-Van were lyophilized, using as cryoprotective agent Sucrose at 3%, and it was observed that after rehydration the nanoparticles return to the original state and there are no significant modifications in size, PDI, ZP, EE and release profile. The antimicrobial activity of the systems was evaluated against reference ATCC strains (methicillin-resistant and methicillin-sensitive SA) by determining the minimum inhibitory concentration and minimum bactericidal concentration. In addition, a death curve was performed for MRSA. These studies showed that vancomycin maintains antimicrobial activity still encapsulated in the nanoparticles.Based on the results obtained, the development of vancomycin-loaded HSA nanoparticles can be considered as an effective approach to prolong the release of the drug and improve the efficacy of local treatment.