title: Preparation and Optimization of Meropenem-Loaded Solid Lipid Nanoparticles: In Vitro Evaluation and Molecular Modeling.
abstract: Encapsulation of antibiotics into nanocarriers has the potential to overcome resistance and disadvantages associated with conventional dosage forms as well as increase half-life of an antibiotic. Encapsulation of meropenem (MRPN) into solid lipid nanoparticles (SLNs) remains unexplored among the limited work reported on nanoformulation incorporating MRPN. The study aimed to use an experimental design, to optimize MRPN-loaded SLNs, and to undertake in vitro and in silico evaluations. A Box-Behnken design (BBD) was used to optimize manufacturing conditions of glycerol monostearate (GMS) SLNs loaded with MRPN. The SLNs were prepared using hot homogenization and ultrasonication method. Optimized MRPN-SLNs showed particle size, zeta potential, and entrapment efficiency of 112.61 ± 0.66 nm, -20.43 ± 0.99 mV, and 89.94 ± 1.26%, respectively. The morphology of the SLNs revealed nearly spherical shaped particles. Differential scanning calorimetry and X-ray diffraction analysis showed that meropenem was present in amorphous form in the SLNs. Controlled in vitro MRPN release from SLNs was achieved and followed the Korsmeyer-Peppas model (R2= 0.9679). Prolonged in vitro antibacterial activity against Escherichia coli was also observed. The molecular modeling showed that both hydrophobic interactions and hydrogen bonding led to a stable MRPN-GMS complex formation, which was confirmed by its low heat of formation (-5536.13 kcal/mol). This stable complex could have contributed to the controlled release of MRPN from the SLNs and subsequent sustained antibacterial activity.
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
authors.forename: Ellen K G
authors.initials: EKG
authors.lastname: Mhango
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa. kalhapure@ukzn.ac.za.
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Kalhapure
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
authors.forename: Mahantesh
authors.initials: M
authors.lastname: Jadhav
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
authors.forename: Sandeep J
authors.initials: SJ
authors.lastname: Sonawane
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
authors.forename: Chunderika
authors.initials: C
authors.lastname: Mocktar
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
authors.forename: Suresh
authors.initials: S
authors.lastname: Vepuri
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Soliman
authors.affiliation: Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa. govenderth@ukzn.ac.za.
authors.forename: Thirumala
authors.initials: T
authors.lastname: Govender
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D002152:Calorimetry, Differential Scanning / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry; D000077731:Meropenem; D008826:Microbial Sensitivity Tests / Q000379:methods; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D013845:Thienamycins / Q000138:chemical synthesis*; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D004337:Drug Carriers; D008055:Lipids; D013845:Thienamycins; D000077731:Meropenem
keywords: Box-Behnken design; antibacterial; meropenem; molecular modeling; solid lipid nanoparticles