Ciprofloxacin Complex Research Articles

Molecular Docking and Dynamic Simulation Approach to Target Penicillin-Binding Protein 1B (LpoB) of Salmonella typhimurium with Flavonoids

Background and Objective: Lipopolysaccharide (LPS) is an essential constituent of the outer membrane of gram-negative bacteria, such as Salmonella typhimurium, and it plays a crucial role by inducing disease in the host. Penicillin-binding protein 1B (LpoB) is a key enzyme in the production of peptidoglycans, making it a potential target for the development of new antimicrobials. Flavonoids are naturally occurring plant-derived chemicals with a wide range of pharmacological properties, including antibacterial capabilities. The goal of this study was to identify the potential flavonoid that inhibits the protein LpoB using computational approaches and compare it with the standard antibiotic ciprofloxacin. Methods: The study was carried out by selecting fifty flavonoids based on Lipinski’s rule of five. Molecular docking was carried out for selected flavonoids and ciprofloxacin against the LpoB protein using AutoDock 4. A 100 nanosecond molecular dynamic simulation was performed for apoprotein, LopB-fisetin, and LpoB-ciprofloxacin complexes, followed by free energy calculation by Molecular Mechanics Generalized Born Surface Area (MMGBSA) solvation analysis. Results: The docking results revealed that fisetin displayed five hydrogen bonds with a binding affinity of -4.67 kcal/mol, and ciprofloxacin exhibited a binding affinity of -4.36 kcal/mol with two hydrogen bonds. The apoprotein and fisetin complex remained stable throughout the 100 ns molecular dynamic simulation, while the ciprofloxacin complex lost its stability. The MMGBSA analysis with fisetin showed better binding free energy compared to ciprofloxacin. Conclusion: The present study has emphasized the potential of flavonoids as probable candidates that can inhibit the protein LpoB. The integration of molecular docking, dynamic simulations, and MMGBSA analysis has provided significant insight into the thermodynamics and binding interactions of the LpoB- fisetin complex, and it has enabled further experimental validations.

Dual-emission ratio fluorescent probe based on carbon dots and copper-silver bimetallic nanoclusters for visual and fluorescent detection of ciprofloxacin

Ciprofloxacin (CIP) plays an important role in many physiological processes. Previously reported methods for CIP detection have many drawbacks and so it is crucial to develop highly sensitive methods to detect CIP. In this study, a dual-emission ratiometric fluorescent probe (SF-CQDs/CuAg NCs) of a nanocomposite of carbon quantum dots (SF-CQDs) and copper-silver bimetallic nanoclusters (CuAg NCs) was developed for sensitive and selective detection of CIP. The fluorescent signal of CuAg NCs was quenched while the fluorescence intensity of SF-CQDs was enhanced in the presence of CIP. The working principle of the fluorescent probe SF-CQDs/CuAg NCs is mainly based on the complexation of CIP with CuAg NCs to free SF-CQDs. The quenching of CuAg NCs by CIP arises from the chelation between the metal and the 1-oxo substituent and the adjacent carboxyl group of CIP. The fluorescence recovery of SF-CQDs is attributing to the release of SF-CQDs from SF-CQDs/CuAg NCs and the hydrogen bonding interaction between SF-CQDs and CIP. The ratiometric fluorescence measurement of SF-CQDs/CuAg NCs has been employed to analyze CIP with good sensitivity and selectivity. The working range of CIP is 5.0–200.0 μM and the detection limit is 3.3 μM. More importantly, the fluorescence of SF-CQDs/CuAg NCs can be detected intuitively via a smartphone which can be applied to determine CIP.

Hydroxyapatite incorporated metakaolin/sludge based geopolymer adsorbent for copper ions and ciprofloxacin removal: Synthesis, characterization and mechanisms

The efficacy of copper Cu(II) adsorption is significantly affected by the presence of antibiotics, such as ciprofloxacin (CIP). Therefore, researchers are highly interested in conducting extensive investigations on the simultaneous adsorption of Cu(II) and CIP. However, most of the adsorbents exhibited low adsorption capacity of CIP with increasing Cu(II) concentration due to the competition for adsorption sites. Hence, the integration of various adsorbents into a single composite could be an effective way to increase the adsorption sites. Thus, this study aims to incorporate hydroxyapatite (Hap) into metakaolin/sludge based geopolymer adsorbent for simultaneous adsorption of Cu(II) and CIP. The effect of different filler loading of Hap (1–3 %) on the metakaolin/sludge geopolymerization and also on the removal efficiency of Cu(II) and CIP were studied in a single and binary system. Moreover, the effects of varied concentrations of Cu(II) (0–100 mg/L) on the removal efficiency of CIP were investigated. Characterization techniques such as x-ray diffraction (XRD), fourier-transform infrared spectrometry (FTIR), scanning electron microscopy (SEM), brunauer-emmett-teller (BET) and neutron tomography imaging were employed to characterize the physicochemical properties of the synthesized geopolymer. It was found that the Hap content has a significant impact on the removal efficiency of CIP and Cu(II). The addition of 2 % Hap providing more nucleation site for the increasing geopolymerization (C-A-S-H) and silicoalumino phosphate gel (SAP) leading to the formation of highly cross-linked geopolymer network and abundant active sites which would favour the adsorption. Moreover, the removal efficiency of CIP by 2 % Hap-geopolymer increased (25.6 % to 61.51 %) with increasing Cu(II) concentration by the complexation and bridging effect between Cu(II) and CIP resulting in the formation of GMK25S1-2Hap-Cu(II)-CIP complexes. Therefore, the hybrid method of geopolymer and Hap is an exceptionally efficient approach for the treatment of wastewater that comprises Cu(II) and CIP.

Computational choreography: dissecting the dance of hydrogen bonding and π–π stacking in the fluorescence discrimination mechanism of ciprofloxacin with supramolecular assembly

The detailed binding insight between the fluorophore and analyte plays a pivotal role in the design of an efficient chemosensor for water pollution. In this study, we designed a picolinic acid-functionalized calix[4]pyrrole ligand (PCACP). When testing out the fluorescence study with selected antibiotics, we observed remarkable enhancement of fluorescence spectra in the presence of ciprofloxacin, singling out the PCACP_Ciprofloxacin complex. The detailed binding mechanism is explored via computational methods including molecular docking and dynamics, DFT (density functional theory) and NBO (Natural Bonding Orbital) analysis. The result of this study provides the comprehensive insight into the involvement of functionalized group of PCACP and ciprofloxacin antibiotic. The results of the computational findings are further explored through NMR complexation study, which corroborate the computational findings. With the limit of detection calculated at 18 µM, we carried out the water sample analysis, which shows promising results. The outcome of this research provides a new, effortless fluorescence approach to monitor the presence of ciprofloxacin in water. In the presence of the ciprofloxacin antibiotic, the fluorescence spectra of PCACP experience remarkable enhancements. This complexation phenomenon is studied through different computational and experimental methods. Communicated by Ramaswamy H. Sarma

Synthesis, XRD, spectroscopic (UV–Vis, IR, EPR) and biological evaluations of cobalt(II)-ciprofloxacin complex as antimicrobial agent: In silico molecular docking and ADME

Cobalt(II)-Ciprofloxacin complex ([Co(Cip)2(H2O)2].2(H2PO4).8(H2O); Cip=Ciprofloxacin) containing phosphoric acid was synthesized and its structure was characterized by numerous analytical techniques such as FT-IR (Fourier Transform Infrared), UV–Vis (Ultraviolet-Visible), EPR (Electron Paramagnetic Resonance), TGA (Thermogravimetric Analysis), elemental analysis and SCXRD (single crystal X-ray diffraction) for structural elucidation. According to XRD data, the environment of Cobalt has octahedral geometry with ciprofloxacin ligand bonded as bidentate (keto and carboxyl group) and aqua ligand. It was revealed that the metal complex left metal oxide and other residues as the final product in the multi-step decomposition TGA curve in the range of 20–1000 °C. The contribution of intermolecular interactions that lead to molecular packing was analyzed using Hirshfeld surface analysis. The synthesized complex was tested for antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans. We conducted a molecular docking study using AUTODOCK 4.2 to investigate the binding energy and interaction modes of a highly potent microbial complex with three different enzymes: S. aureus DNA gyrase (PDB ID: 2XCT), GyrA (PDB ID: 3LPX), and mycobacterium tuberculosis gyrase type IIA topoisomerase (PDB ID: 3UC1).

Chitosan nanofibrous scaffold with graded and controlled release of ciprofloxacin and BMP-2 nanoparticles for the conception of bone regeneration

The repair of bone defects using grafts is commonly employed in clinical practice. However, the risk of infection poses a significant concern. Tissue engineering scaffolds with antibacterial functionalities offer a better approach for bone tissue repair. In this work, firstly, two kinds of nanoparticles were prepared using chitosan to complex with ciprofloxacin and BMP-2, respectively. The ciprofloxacin complex nanoparticles improved the dissolution efficiency of ciprofloxacin achieving a potent antibacterial effect and cumulative release reached 95 % in 7 h. For BMP-2 complexed nanoparticles, the release time points can be programmed at 80 h, 100 h or 180 h by regulating the number of coating chitosan layers. Secondly, a functional scaffold was prepared by combining the two nanoparticles with chitosan nanofibers. The microscopic nanofiber structure of the scaffold with 27.28 m2/g specific surface area promotes cell adhesion, high porosity provides space for cell growth, and facilitates drug loading and release. The multifunctional scaffold exhibits programmed release function, and has obvious antibacterial effect at the initial stage of implantation, and releases BMP-2 to promote osteogenic differentiation of mesenchymal stem cells after the antibacterial effect ends. The scaffold is expected to be applied in clinical bone repair and graft infection prevention.

PK-PD Evaluation of Inhaled Microparticles loaded with Ciprofloxacin-Copper complex in a Rat Model of Chronic Pseudomonas aeruginosa Lung Infection.

The potential gain in efficacy of pulmonary administration over IV administration of some antibiotics such as ciprofloxacin (CIP) may be limited by the short residence time of the drug at the site of infection after nebulization. Complexation of CIP with copper reduced its apparent permeability in vitro through a Calu-3 cell monolayer and greatly increased its pulmonary residence time after aerosolisation in healthy rats. Chronic P. aeruginosa lung infections in cystic fibrosis patients result in airway and alveolar inflammation that may increase the permeability of inhaled antibiotics and alter their fate in the lung after inhalation compared to what was seen in healthy conditions. The objective of this study was to compare the pharmacokinetics and efficacy of CIP-Cu2+ complex-loaded microparticles administered by pulmonary route with a CIP solution administered by IV to model rats with chronic lung infection. After a single pulmonary administration of microparticles loaded with CIP-Cu2+ complex, pulmonary exposure to CIP was increased 2077-fold compared to IV administration of CIP solution. This single lung administration significantly reduced the lung burden of P. aeruginosa expressed as CFU/lung measured 24 h after administration by 10-fold while IV administration of the same dose of CIP was ineffective compared to the untreated control. This better efficacy of inhaled microparticles loaded with CIP-Cu2+ complex compared with CIP solution can be attributed to the higher pulmonary exposure to CIP obtained with inhaled CIP-Cu2+ complex-loaded microparticles than that obtained with IV solution.

SPECTRAL, MAGNETIC AND BIOLOGICAL STUDIES OF MECHANOCHEMICAL SYNTHESIS OF METAL (II) COMPLEXES DERIVED FROM CIPROFLOXACIN

The mechanically synthesized complexes of ciprofloxacin were characterized by physical methods, spectral and biological studies. Spectral studies show that; in the complexes, the ciprofloxacin acted as bidentate ligand which coordinated to the metal ion through the ring carbonyl oxygen and one of the Oxygen atoms of the carboxylate group. Results from microanalysis data shows 1:2 metals to ligand ratio. All the complexes show strong antibacterial activity at all concentrations compared with the free ligand (ciprofloxacin).

Mixed-ligand copper(ii) complexes of guanidine derivatives containing ciprofloxacin: synthesis, characterization, DFT calculations, DNA interactions and biological activities

Two copper(ii) complexes of guanidine derivatives and ciprofloxacin are good candidates for the next generation of anticancer and/or antibacterial agents.

Graphene oxide modified screen-printed electrode for highly sensitive and selective electrochemical detection of ciprofloxacin residues in milk

The monitoring of antibiotic residues in foodstuffs by using rapid detection method is essential for food safety. In this work, the electrochemical sensor was developed by modification of screen-printed carbon electrode with graphene oxide, and then the ciprofloxacin (CIP) was detected based on the complexation of CIP with Mn2+. On modified electrode, the anodic stripping peak current response of Mn2+ was prohibited in the presence of CIP, and a peak current response of the complex was occurred. Thus, the peak current response of the complexation peak was employed as the indicating signal for CIP determination, which was more sensitive than the direct electrochemical oxidation response of CIP. Parameters that affect the signal response have been investigated in method. Under the optimum conditions, the peak current of the complexation peak was linearly correlated with the CIP content in the milk sample solution at 1.0 to 8.0 μM, and the linear correlation coefficients (R2) was 0.994. The limits of detection (LOD) was 0.30 μM. Recoveries of CIP in milk sample were ranged from 81.0 to 95.4% with relative standard deviations (RSDs) below 4.6%. The method showed high selectivity and sensitive, good reproducibility, indicated that this method has potential to be applied in CIP residue analysis.

Synthesis, spectroscopic and thermogravimetric interpretations of UO2(II), ZrO(II), Zr(IV), VO(II) and V(V) ciprofloxacin antibiotic drug complexes

Abstract New five ciprofloxacin (CIP) complexes of dioxouranium(II), oxozirconium(II), zirconium(IV), oxovanadium(II) and vanadium(IV) in the proportion 1:2 have been prepared using CIP as a drug chelate with UO2(NO3)2. 6H2O, ZrOCl2. 8H2O, ZrCl4, VOSO4. xH2O and V2O5 respectively. The CIP complexes have been characterized based on the elemental analysis, molar conductance, magnetic, (FTIR & 1HNMR) spectral and thermal studies. The molar conductance studies of the synthesized complexes in DMSO solvent with concentration of 10–3 M indicate their non-electrolytic properties. At room temperature, the magnetic moment measurements revealed a diamagnetic behavior for all CIP prepared complexes. The different formulas of the new complexes can be represented as [UO2(CIP)2(NO3)2] (I), [VO(CIP)2(SO4)(H2O)] (II), [V2(O)(O2)2(CIP)2] (III), [Zr(O)(CIP)2(Cl)2] (IV), and [Zr(CIP)2(Cl)4] (V). The thermal analysis data of the complexes indicates the absence of coordinated water molecules except for vanadyl(II) complex (II). The CIP chelate is a uni-dentate ligand coordinated to the mentioned metal ion through terminal piperazinyl nitrogen. The transmission electron microscopy (TEM) investigation confirms the nano-structured form of the complexes.

Structural elucidation of Levofloxacin and Ciprofloxacin using density functional theory and Raman spectroscopy with inexpensive lab-built setup

In the present work, we have investigated the structures of fluoroquinolones Levofloxacin and Ciprofloxacin using Raman spectroscopy and density functional theory calculations. The Raman spectra of Levofloxacin and Ciprofloxacin were recorded with lab-built inexpensive Raman spectroscopy setup that uses 638 nm laser diode. Raman spectra in the fingerprint spectral region (900–1800 cm−1) were investigated for both the molecules. The density functional theory (DFT) utilizing B3LYP functional with 6-31+G(d,p) basis set was used to investigate the minimum energy structures of two molecules along with the calculation of Raman spectrum. Molecular complexes of Levofloxacin and Ciprofloxacin with one and two water molecules were also studied to see the effect of H-bonding on Raman spectra. It was found that the conformation and orientation of piperazine ring along with the orientation of hydroxyl group plays a vital role in determination of the minimum energy structure. The calculated Raman spectra of bare molecules and their complexes with water molecules were compared to the experimental Raman spectra. The calculated Raman spectrum of minimum energy structure was found to be in good agreement with the experimental spectrum. Further it was observed that the experimental Raman spectrum is better explained when H-bonding is considered, which could be due to the water molecule or the dimer formation of the molecules under investigation.

In vivo efficacy of a dry powder formulation of ciprofloxacin-copper complex in a chronic lung infection model of bioluminescent Pseudomonas aeruginosa

A significant limitation of locally delivered treatments for chronic pulmonary infections is often the short residence time within the airways. Ciprofloxacin (CIP), for example, undergoes rapid absorption from the airway lumen. Previously, we demonstrated that the complexation of CIP with copper (CIP-Cu) reduces its apparent epithelial permeability and pulmonary absorption rate without affecting antimicrobial activity against Pseudomonas aeruginosa grown planktonically or as biofilms. This study aimed to evaluate the in vivo efficacy of CIP-Cu, prepared as a dry powder, in a chronic lung infection model. The powders were prepared by jet milling (CIP-HCl) and by spray drying (CIP-Cu). A bioluminescent strain of P. aeruginosa (PAO1::p16Slux) was used to prepare bacteria-loaded agar beads that were inoculated intratracheally to rats. The dynamics of the infection were monitored using luminometry. The bacteria/beads ratio was optimized to allow the highest luminescence signal and animal survival for 8 days. The efficacy of the treatment was evaluated by luminometry in addition to the end-point (Day 8) where colony counting was performed after lung harvesting. Luminescent P. aeruginosa entrapped in agar beads were useful to monitor the spatial development of the chronic lung infection in rats. The rats were treated with the dry powders in a nose-only inhalation exposure system (NOIES). CIP-Cu and CIP-HCl powders showed similar aerodynamic properties and comparable CIP lung deposition. However, treatment with CIP-Cu significantly (p < 0.01) reduced by 4-log the number of CFU of P. aeruginosa per lung in the chronic infection model, whereas CIP-HCl effect was not different from the untreated control group.

Synthesis, characterization and\xa0assessment of anti-quorum sensing activity of copper(II)-ciprofloxacin complex against Pseudomonas aeruginosa PAO1

Quorum sensing (QS) inhibition by metal-antibiotic complexes is a promising strategy for the management and control of multidrug resistant Pseudomonas aeruginosa infections. We investigated the anti-quorum sensing activity of sub-minimum inhibitory concentration (sub-MIC) of copper(II) sulfate pentahydrate-ciprofloxacin (Cu-CIP) complex and free ciprofloxacin (free-CIP) against P. aeruginosa PAO1. Copper-CIP complex was synthesized and its characterization was assessed using spectroscopic methods and single crystal X-ray analysis. The effect of sub-MIC (1/4 and 1/16 MIC) concentrations of Cu-CIP and free-CIP on cell growth, biofilm formation, motility, alginate and pyocyanin production, H2O2 susceptibility and expression of QS circuit genes lasI and lasR in PAO1 was determined. Minimum inhibitory concentration of Cu-CIP complex and free-CIP was determined as 0.125 µg/ml. Copper-CIP complex did not show significant effect on the cell growth at concentrations of 1/4 and 1/16 MIC. However, sub-MIC concentrations (1/4 and 1/16 MIC) of Cu-CIP showed the significant reduction in violacein production, motility, biofilm formation, alginate and pyocyanin production and sensitivity to H2O2 in a concentration dependent manner (P < 0.001). Copper-CIP at the concentration of 1/4 MIC showed the greatest reduction in lasI and lasR transcriptional expression (89.5% and 96.2% respectively). Considering the biological effects of Cu-CIP complex and its inhibitory activity on QS related virulence traits at low concentrations (0.03 and 0.007 µg/ml), it may be used as an effective approach in the management of infections caused by P. aeruginosa.

Effective and efficient detection of pH fluctuations based on ratiometric metallic-ciprofloxacin architectures

The availability of lanthanide ciprofloxacin complexes and the exploration of efficient new ways to the target species have made fluorescent signals as essential tools for chemical sensing. Both terbium (III) and europium (III) compounds possess easily distinguished, line-like emission bands occurring in the green and red region respectively. Based on the steps of ionizations and the coordination structure changes, the two molecular probes give rise to unique pH-sensitivities at different conditions. The photoluminescence properties of the mixture for the two complexes are demonstrated. At pH from 3 to 6, the Eu(III) emission is found to be less affected and the solution emits blue light in acidic environment (pH = 3). The terbium (III) characteristic luminescence exhibited off-on changes within a narrow pH range (pH = 5–6). Further spectroscopic pH titrations (pH from 6 to 10) are performed and the Eu (III) red emission has been significantly improved. The molecular-based probes have excellent water solubility, negligible cytotoxicity and enough permeability to across cell membrane. Such pH-responsive performance has been carried out for the investigation of intracellular pH measurement and these novel pH indicators were considered to be suitable for detecting bio-medical samples.

FORMULATION AND EVALUATION OF TASTE MASKED ORAL DISPERSIBLETABLET OF CIPROFLOXACIN WITH ION EXCHANGE RESIN

Bitter taste is one of the important formulation problems that are encountered with many drugs, like Ciprofloxacin. In modern times, the most improved & easy technique is to formulate tasteless complexes of ciprofloxacin with ion exchange resin (Indion 234). After acid activation and swelling in water, resin & ciprofloxacin (proper ratio) was stirred for definite time & unbound drug in filtrate was estimated spectrophotometrically and drug-loading efficiency was calculated. The molecular properties of drug complexes by FT-IR study confirm the complexation of ciprofloxacin with Indion 234. The influence of superdisintegrants, crospovidone and sodium starch glycolate on disintegration time, wetting time and water absorption ratio was studied.

Highly sensitive Eu3+ doped in sol-gel matrix optical sensor for the assessment of Ciprofloxacin in different real samples

The efficiency of excited-state interaction between Eu3+ doped in sol- gel matrix and the industrial product ciprofloxacin of (CFX) has been studied in different solvent and pHs. A high luminescence intensity peak at 617 nm of europium- ciprofloxacin complex at λex=365 nm in acetonitrile was obtained. The photophysical properties of the red emissive Eu3+ complex doped in sol-gel matrix have been elucidated, the europium was used as optical sensor for the assessment of ciprofloxacin in the pharmaceutical tablets and serum samples at pH 8.0 and λex = 365 nm with a concentration range of 5.0 ×10−9 - 1.0 ×10−6 mol L−1 for ciprofloxacin, correlation coefficient of 0.99 and detection limit of 1.65 ×10−9 mol L−1.

Development of a novel ‘nanocarrier’ system based on Halloysite Nanotubes to overcome the complexation of ciprofloxacin with iron: An in vitro approach

The bioavailability of ciprofloxacin (CIP) is known to decrease upon administration due to its complexation with iron present in the body. A possible way to prevent this complexation is by entrapping the drug in a carrier. In this study, Halloysite Nanotubes (HNT) post functionalization with 3-aminopropyltriethoxysilane (APTES) were used as ‘nanocarrier’ for the entrapment of CIP. The complexation studies between CIP and iron revealed 71%±1.2% decrease in drug's absorbance upon complexation. Further, the in vitro antibacterial studies also exhibited a reduction in the antibacterial property of CIP on complexation with iron. Pristine HNT exhibited no interaction with CIP and iron. But post functionalization, the nanotubes had a strong interaction with iron and removed 80%±0.9% of it from the solution. Drug loading studies using functionalized HNT (fHNT) presented a 70%±1.7% loading of CIP on it. The samples of HNT (before and after functionalization and after drug loading) were characterized with TEM, XRD, FTIR and DSC. The drug release studies exhibited a sustained release of CIP from drug loaded fHNT. Further, drug loaded fHNT (CIP-fHNT) removed iron from the iron-rich solution and released the loaded drug back into the solution.

Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections

Current pulmonary treatments against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lung suffer from deactivation of the drug and immobilization in thick and viscous biofilm/mucus blend, along with the general antibiotic resistance. Administration of nanoparticles (NPs) with high antibiotic load capable of penetrating the tight mesh of biofilm/mucus can be an advent to overcome the treatment bottlenecks. Biodegradable and biocompatible polymer nanoparticles efficiently loaded with ciprofloxacin complex offer a solution for emerging treatment strategies. NPs were prepared under controlled conditions by utilizing MicroJet Reactor (MJR) to yield a particle size of 190.4±28.6nm with 0.089 PDI. Encapsulation efficiency of the drug was 79% resulting in a loading of 14%. Release was determined to be controlled and medium-independent in PBS, PBS+0.2% Tween 80 and simulated lung fluid. Cytotoxicity assays with Calu-3 cells and CF bronchial epithelial cells (CFBE41o−) indicated that complex-loaded PLGA NPs were non-toxic at concentrations ≫ MICcipro against lab strains of the bacteria. Antibacterial activity tests revealed enhanced activity when applied as nanoparticles. NPs’ colloidal stability in mucus was proven. Notably, a decrease in mucus turbidity was observed upon incubation with NPs. Herewith, ciprofloxacin complex-loaded PLGA NPs are introduced as promising pulmonary nano drug delivery systems against P.aeruginosa infections in CF lung.

Optimization of ciprofloxacin complex loaded PLGA nanoparticles for pulmonary treatment of cystic fibrosis infections: Design of experiments approach

Design of Experiments (DoE) is a powerful tool for systematic evaluation of process parameters’ effect on nanoparticle (NP) quality with minimum number of experiments. DoE was employed for optimization of ciprofloxacin loaded PLGA NPs for pulmonary delivery against Pseudomonas aeruginosa infections in cystic fibrosis (CF) lungs. Since the biofilm produced by bacteria was shown to be a complicated 3D barrier with heterogeneous meshes ranging from 100nm to 500nm, nanoformulations small enough to travel through those channels were assigned as target quality. Nanoprecipitation was realized utilizing MicroJet Reactor (MJR) technology based on impinging jets principle. Effect of MJR parameters flow rate, temperature and gas pressure on particle size and PDI was investigated using Box-Behnken design. The relationship between process parameters and particle quality was demonstrated by constructed fit functions (R2=0.9934 p<0.0001 and R2=0.9983 p<0.0001, for particle size and PDI, respectively). Prepared nanoformulations varied between 145.2 and 979.8nm with PDI ranging from 0.050 to 1.00 and showed encapsulation efficiencies >65%. Response surface plots provided experimental data-based understanding of MJR parameters’ effect, thus NP quality. Presented work enables ciprofloxacin loaded PLGA nanoparticle preparations with pre-defined quality to fulfill the requirements of local drug delivery under CF disease conditions.