Gentamicin Sulfate PEG-PLGA/PLGA-H Nanoparticles: Screening Design and Antimicrobial Effect Evaluation toward Clinic Bacterial Isolates

Abstract

Nanotechnology is a promising approach both for restoring or enhancing activity of old and conventional antimicrobial agents and for treating intracellular infections by providing intracellular targeting and sustained release of drug inside infected cells. The present paper introduces a formulation study of gentamicin loaded biodegradable nanoparticles (Nps). Solid-oil-in water technique was studied for gentamicin sulfate nanoencapsulation using uncapped Polylactide-co-glycolide (PLGA-H) and Polylactide-co-glycolide-co-Polyethylenglycol (PLGA-PEG) blends. Screening design was applied to optimize: drug payload, Nps size and size distribution, stability and resuspendability after freeze-drying. PLGA-PEG concentration resulted most significant factor influencing particles size and drug content (DC): 8 w/w% DC and 200 nm Nps were obtained. Stirring rate resulted most influencing factor for size distribution (PDI): 700 rpm permitted to obtain homogeneous Nps dispersion (PDI = 1). Further experimental parameters investigated, by 23 screening design, were: polymer blend composition (PLGA-PEG and PLGA-H), Polyvinylalcohol (PVA) and methanol concentrations into aqueous phase. Drug content was increased to 10.5 w/w%. Nanoparticle lyophilization was studied adding cryoprotectants, polyvinypirrolidone K17 and K32, and sodiumcarboxymetylcellulose. Freeze-drying protocol was optimized by a mixture design. A freeze-dried Nps powder free resuspendable with stable Nps size and payload, was developed. The powder was tested on clinic bacterial isolates demonstrating that after encapsulation, gentamicin sulfate kept its activity.

Nano-in-Micro Dual Delivery Platform for Chronic Wound Healing Applications

“…The calculated half-maximal inhibitory (IC 50 ) and minimum inhibitory (MIB) concentrations are shown in Figure 5E,F. The obtained values are in accordance with results reported previously [21,22,42].…”

“…Gentamicin-loaded poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) were prepared using a water-in-oil-in-water (W/O/W) double emulsification evaporation process, as previously reported [20][21][22]. Resomer RG 503 PLGA (50:50; molecular weight: 28 kg/mol) was used in this study.…”

Dexibuprofen Biodegradable Nanoparticles: One Step Closer towards a Better Ocular Interaction Study

“…Moreover, PEG has been widely used to reduce the clearance of PLGA nanoparticles (NPs) and it has been demonstrated that PEG coatings shield the surface from aggregation, opsonization, phagocytosis and prolong nanoparticles systemic circulation time [5]. Poly(ethylene glycol) (PEG) is a non-ionic, hydrophilic, polyether synthesized by polymerization of the monomer ethylene glycol and can be obtained in a wide range of molecular weights [7,8].…”

Toxicity Studies of Oral and Transdermal Formulations of Gentamicin Loaded PLGA Nanoparticles in Animal Model

“…Gentamicin, an aminoglycoside, is used for treating various bacterial infections like endocarditis, bone infections, meningitis, urinary tract infections, pneumonia and sepsis. It is favored antibiotic for treatment of nosocomial infections caused by Staphylococcus aureus, Pseudomonas aeruginosa and E.coli (Dorati et al, 2018). It has poor cellular penetration and high water solubility that's why placed in class III of BCS (British pharmaceutical classification system) (Sabaeifard et al, 2016).…”

“…Like other aminoglycosides, gentamicin has low bioavailability and short half-life (Abdelghany et al, 2012). The conventional regimens of gentamicin multiple dosing result in various adverse effects due to its hostile biodistribution and fast clearance resulting in hepatotoxicity and nephrotoxicity (Dorati et al, 2018). The most convenient site of aminoglycoside injury is epithelial cells of kidney proximal tubules.…”