Systematic Approach for the Formulation and Optimization of Solid Lipid Nanoparticles of Efavirenz by High Pressure Homogenization Using Design of Experiments for Brain Targeting and Enhanced Bioavailability

Abstract

The nonnucleoside reverse transcriptase inhibitors, used for the treatment of HIV infections, are reported to have low bioavailability pertaining to high first-pass metabolism, high protein binding, and enzymatic metabolism. They also show low permeability across blood brain barrier. The CNS is reported to be the most important HIV reservoir site. In the present study, solid lipid nanoparticles of efavirenz were prepared with the objective of providing increased permeability and protection of drug due to biocompatible lipidic content and nanoscale size and thus developing formulation having potential for enhanced bioavailability and brain targeting. Solid lipid nanoparticles were prepared by high pressure homogenization technique using a systematic approach of design of experiments (DoE) and evaluated for particle size, polydispersity index, zeta potential, and entrapment efficiency. Particles of average size 108.5 nm having PDI of 0.172 with 64.9% entrapment efficiency were produced. Zeta potential was found to be −21.2 mV and the formulation was found stable. The in-vivo pharmacokinetic studies revealed increased concentration of the drug in brain, as desired, when administered through intranasal route indicating its potential for an attempt towards complete eradication of HIV and cure of HIV-infected patients.

Improved antibacterial function of Rifampicin-loaded solid lipid nanoparticles on Brucella abortus

“…Homogenization or ultrasonic technique is a simple method for producing nanoparticles in large-scale without the need for organic solvents and complex equipment [11]. In this study, a Magnetic Stirrer (Magnetic Heater) was used instead of a high shear homogenizer to prevent metal contamination and to increase PDI [34,35]. This method is a suitable structural model for encapsulating lipophilic drugs such as Rifampicin in SLNs regarding purposes for which it needs to be protected from deactivation and therefore it can be released slowly.…”

“…Stearic acid is a fatty acid (molecular weighing 284.48) with a medium-chain and negative charge at neutral pH, compared to the characteristics of any solid lipid, it is clear that stearic acid is the best choice for Rifampicin due to its good solubility in this lipid and the higher drug-loading potential [21,[35][36][37][38]. In the optimal formulation, 2% of stearic acid was used that particle size was between 300 and 400 nm, but in the formulation of more than 2.5%, particle size was reached to more than 500 nm.…”

(Bio)conjugation Strategies Applied to Fluorescent Semiconductor Quantum Dots

“…A suspension with good colloidal stability (ζ > + 20 mV or < −20 mV) should not show aggregation, as a result of mutual electrostatic repulsion between the particles. 124 In addition, a modification process on QDs' surface (e.g., ligand addition) could be also evaluated using zeta potential analysis. 123 Ipe et al 125 reported the use of DLS and zeta potential techniques to confirm the protein cytochrome P450 BSβ conjugation with CdS and CdSe QDs.…”

<p>Lipid-Based Gliclazide Nanoparticles for Treatment of Diabetes: Formulation, Pharmacokinetics, Pharmacodynamics and Subacute Toxicity Study</p>

“…1 In addition, the scaling up of the formulation technique to industrial production level is feasible at low cost and in a relatively simple way. 2 Gliclazide is an oral hypoglycemic useful for the treatment of non-insulin-dependent diabetes mellitus. Gliclazide exhibits slow GI absorption rate and wide inter individual variations in absorption and bioavailability.…”