A PEGylated Nanostructured Lipid Carrier for Enhanced Oral Delivery of Antibiotics

Abstract

Antimicrobial resistance is a major concern for public health throughout the world that severely restricts available treatments. In this context, methicillin-resistant Staphylococcus aureus (MRSA) is responsible for a high percentage of S. aureus infections and mortality. To overcome this challenge, nanoparticles are appropriate tools as drug carriers to improve the therapeutic efficacy and decrease the toxicity of drugs. In this study, a polyethylene glycol (PEG)ylated nanostructured lipid carrier (PEG-NLC) was synthesized to improve the oral delivery of trimethoprim/sulfamethoxazole (TMP/SMZ) for the treatment of MRSA skin infection in vitro and in vivo. The nanoformulation (PEG-TMP/SMZ-NLC) was synthesized with size and drug encapsulation efficiencies of 187 ± 9 nm and 93.3%, respectively, which could release the drugs in a controlled manner at intestinal pH. PEG-TMP/SMZ-NLC was found efficient in decreasing the drugs’ toxicity by 2.4-fold in vitro. In addition, the intestinal permeability of TMP/SMZ was enhanced by 54%, and the antibacterial effects of the drugs were enhanced by 8-fold in vitro. The results of the stability study demonstrated that PEG-TMP/SMZ-NLC was stable for three months. In addition, the results demonstrated that PEG-TMP/SMZ-NLC after oral administration could decrease the drugs’ side-effects such as renal and hepatic toxicity by ~5-fold in MRSA skin infection in Balb/c mice, while it could improve the antibacterial effects of TMP/SMZ by 3 orders of magnitude. Overall, the results of this study suggest that the application of PEGylated NLC nanoparticles is a promising approach to improving the oral delivery of TMP/SMZ for the treatment of MRSA skin infection.

An Overview of Polymeric Nanoplatforms to Deliver Veterinary Antimicrobials

“…In a follow-up study conducted by the same research group, a PEGylated nanostructured lipid carrier (NLC) was used for testing the oral delivery of trimethoprim/sulfamethoxazole (TMP/SMZ), and the PLH system was evaluated by examining the antimicrobial properties of antibiotics [ 105 ]. PEG-TMP/SMZ-NLCs were obtained at a size of 187 ± 9 nm using the melt emulsification method.…”

“…The results indicated the importance of PEG in PLH systems, in which the smaller size, higher encapsulation capacity, and slower drug release were the main advantages for the higher antimicrobial efficacy of PEG-Lip-NF. In a follow-up study conducted by the same research group, a PEGylated nanostructured lipid carrier (NLC) was used for testing the oral delivery of trimethoprim/sulfamethoxazole (TMP/SMZ), and the PLH system was evaluated by examining the antimicrobial properties of antibiotics [105]. PEG-TMP/SMZ-NLCs were obtained at a size of 187 ± 9 nm using the melt emulsification method.…”

“…Similar findings were reported by Sajedehsadat et al [110], who further pointed out that the polymer materials in the PLH system could improve the oral absorption of drugs. Meanwhile, the main mechanisms of this system were stated, which were (1) promoting the mucosal interaction, (2) increasing the residence time of drugs in the GI tract, (3) enhancing drug solubility and inhibiting In a follow-up study conducted by the same research group, a PEGylated nanostructured lipid carrier (NLC) was used for testing the oral delivery of trimethoprim/sulfamethoxazole (TMP/SMZ), and the PLH system was evaluated by examining the antimicrobial properties of antibiotics [105]. PEG-TMP/SMZ-NLCs were obtained at a size of 187 ± 9 nm using the melt emulsification method.…”

Design, Evaluation and Comparison of Nanostructured Lipid Carriers and Chitosan Nanoparticles as Carriers of Poorly Soluble Drugs to Develop Oral Liquid Formulations Suitable for Pediatric Use

“…In vitro drug release experiments from lipid and polymeric nanoparticles have been carried out according to the dialysis membrane method [33]. The dialysis bags (Spectra/Por ® Biotech-Grade Cellulose Ester dialysis membranes, MWCut-Off: 100 kDa, Repligen, Waltham, CA, USA) were filled with 1 mL of sample and immersed under stirring (300 rpm) for 2 h in 15 mL of simulated gastric fluid without pepsin (SGF) at 37 • C, composed from 2.0 g/L NaCl adjusted with HCl 0.1 N at pH 1.2 or at pH 4.5 (this last miming of the gastric pH of infant age < 12 months) [34], and for 4 h in 15 mL of simulated intestinal fluid (SIF) at pH 6.8 (6.80 g/L KH 2 PO 4 and NaOH 0.89 g/L) at 37 • C. Samples of 200 µL were taken at predetermined intervals up to 360 min from the receiver solution and replaced by fresh medium, in order to guarantee sink conditions.…”