A Method for Efficient Loading of Ciprofloxacin Hydrochloride in Cationic Solid Lipid Nanoparticles: Formulation and Microbiological Evaluation

Abstract

The aim of the study was the production of solid lipid nanoparticles (SLN) loaded with ciprofloxacin (CIP) through two different production techniques, quasi-emulsion solvent diffusion (QESD) and solvent injection (SI). In order to efficaciously entrap the commercial salt form (hydrochloride) of the antibiotic in these lipid systems, a conversion of CIP hydrochloride to the free base was realized in situ, through the addition of triethylamine. To ensure physical stability to the carriers over time and ameliorate the interaction with bacterial cell membranes, positively charged SLN were produced by addition of the cationic lipid didecyldimethylammonium bromide (DDAB). Homogeneous SLN populations with a mean particle sizes of 250–350 nm were produced by both methods; drug encapsulation was over 85% for most samples. The SLN were physically stable for up to nine months both at 4 °C and 25 °C, although the former condition appears more suitable to guarantee the maintenance of the initial particle size distribution. As expected, CIP encapsulation efficiency underwent a slight reduction after nine months of storage, although the initial high drug content values would ensure a residual concentration of the antibiotic in the SLN still appropriate to exert an acceptable antibacterial activity. Selected SLN formulations were subjected to an in vitro microbiological assay against different bacterial strains, to verify the effect of nanoencapsulation on the cell growth inhibitory activity of CIP. In general, CIP-SLN produced without DDAB showed MIC values for CIP comparable to those of the free drug. Conversely, addition of increasing percentages of the cationic lipid, reflected by a progressive increase of the positive value of the Zeta potential, showed a variety of MIC values against the various bacterial strains, but with values 2–4 order of dilution lower than free CIP. An hypothesis of the effect of the cationic lipid upon the increased antibacterial activity of CIP in the nanocarriers is also formulated.

Enhancement of ciprofloxacin activity by incorporating it in solid lipid nanoparticles

“…The positively charged SLN has high potential to trigger the antibacterial activity as a result of higher penetration to bacterial cell walls. This was reported recently by Pignatello et al [16]. They prepared positively charged SLN using the cationic lipid didecyldimethylammonium bromide and they rendered the CIP HCl salt to the basic form in order to achieve high zeta and high EE [16].…”

Lipid-Based Nanocarriers for Ophthalmic Administration: Towards Experimental Design Implementation

“…±20 mV) are of interest, since lower values might be overcome by attractive forces between particles, leading to formulation instability [ 101 , 102 ]. In addition, following a topical administration route, the presence of a cationic surface charge is believed to improve residence time by interaction with the negatively charged corneal epithelium and the mucins from the tear fluid and the conjunctiva [ 103 , 104 , 105 ]. High drug loading and entrapment efficiency are also desirable variables to be optimised through DoE.…”

Development of Inhalable Nanostructured Lipid Carriers for Ciprofloxacin for Noncystic Fibrosis Bronchiectasis Treatment

“…The encapsulation efficiency (EE) and Loading Capacity (LC) of CIP in the NLCs were indirectly determined by measuring the concentration of free CIP in the aqueous phase, according to Pignatello et al 28 and analyzed by above mentioned HPLC method (CIP Quantification by HPLC). The EE was estimated using Eq.…”