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Purpose: Antimicrobial resistance is a major health hazard worldwide. Combining azithromycin (AZ) and ciprofloxacin (CIP) in one drug delivery system was proposed to boost their antibacterial activity and overcome resistance. This study aims to improve azithromycin and ciprofloxacin activity by co-encapsulating them inside chitosan-coated polymeric nanoparticles and evaluating their antibacterial activity. Methods: The double emulsion method was employed to co-encapsulate AZ/CIP inside chitosan-coated polymeric nanoparticles. The formulations were evaluated for their nanoparticle size, size distribution, and zeta potential. Differential scanning calorimetry (DSC) analysis characterized the formula's thermal sustainability. Encapsulation efficiency was measured by HPLC and spectrophotometric analysis. Morphological studies used the Transmission Electron Microscopy (TEM). The in vitro release profiles of both AZ and CIP were monitored utilizing the dialysis membrane bag method. The micro-dilution assay assessed the antimicrobial activity against a clinical isolate of Klebsiella pneumoniae. Results: The prepared AZ/CIP-poly-caprolactone nanoparticles were spherical; their size range was 184.0 ± 3.3-190.4 ± 5.6 nm and had high size uniformity (poly-dispersity index below 0.2). The zeta potential ranged from -21.2 ± 2.4 to -27.0 ± 2.5 mV, while chitosan-coated nanoparticles showed a positive zeta potential value ranging from 8 to 11 mV. The thermal study confirmed the amorphous state of both antibiotics inside the nanoparticles. The results of the in vitro release study indicated a slow and uniform rate of release for both drugs extended over 4-days, with a faster rate in the case of AZ. The MIC values reported for both chitosan-coated NP have been tremendously reduced by at least 15 folds of pure CIP and more than 60 folds of pure AZ. Conclusion: The co-encapsulation of AZ/CIP into chitosan-coated polymeric nanoparticles has been successfully achieved. The produced particles showed many beneficial attributes of uniform particle sizes below 200 nm and high zeta potential values. Chitosan-coated polymeric nanoparticles extensively enhanced the antibacterial activity of both AZ/CIP against bacteria.

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Valsartan (Val) is an important antihypertensive medication with poor absorption and low oral bioavailability. These constraints are due to its poor solubility and dissolution rate. The purpose of this study was to optimize a mixed micelle system for the transdermal delivery of Val in order to improve its therapeutic performance by providing prolonged uniform drug levels while minimizing drug side effects. Thin-film hydration and micro-phase separation were used to produce Val-loaded mixed micelle systems. A variety of factors, including the surfactant type and drug-to-surfactant ratio, were optimized to produce micelles with a low size and high Val entrapment efficiency (EE). The size, polydispersity index (PDI), zeta potential, and drug EE of the prepared micelles were all measured. The in vitro drug release profiles were assessed using dialysis bags, and the permeation through abdominal rat skin was assessed using a Franz diffusion cell. All formulations had high EE levels exceeding 90% and low particle charges. The micellar sizes ranged from 107.6 to 191.7 nm, with average PDI values of 0.3. The in vitro release demonstrated a uniform slow rate that lasted one week with varying extents. F7 demonstrated a significant (p < 0.01) transdermal efflux of 68.84 ± 3.96 µg/cm2/h through rat skin when compared to the control. As a result, the enhancement factor was 16.57. In summary, Val-loaded mixed micelles were successfully prepared using two simple methods with high reproducibility, and extensive transdermal delivery was demonstrated in the absence of any aggressive skin-modifying enhancers.

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Ciprofloxacin (CIP), a widely used antibiotic, is a poor biopharmaceutical resulting in low bioavailability. We optimized a CIP polymer-lipid hybrid nanoparticle (CIP-PLN) delivery system to enhance its biopharmaceutical attributes and the overall therapeutic performance. CIP-PLN formulations were prepared by a direct emulsification-solvent-evaporation method. Varying the type and ratio of lipid was tried to optimize a CIP-PLN formulation. All the prepared formulations were evaluated for their particle size, polydispersity index, zeta potential, physical stability, and drug entrapment efficiency. The drug in vitro release profile was also studied. Antibacterial activities were tested by the agar diffusion method for all CIP-PLN formulations against an Escherichia coli clinical bacterial isolate (EC04). CIP-PLN formulations showed average sizes in the range of 133.9 ± 1.7 nm to 217.1 ± 0.8 nm, exhibiting high size uniformity as indicated by polydispersity indices lower than 0.25. The entrapment efficiency was close to 80% for all formulations. The differential scanning calorimetry (DSC) thermograms indicated the existence of CIP in the amorphous state in all PLN formulations. Fourier transform infrared spectra indicated deep incorporation of molecular CIP within the polymer matrix. The release profile of CIP from PLN formulas showed a uniform prolonged drug profile, extended for a week from most formulations with a zero-order kinetics. The antibacterial activity of CIP-PLN formulations showed significantly higher antibacterial activity only with F4 containing lecithin as the lipid component. In conclusion, we successfully optimized a CIP-PLN formulation with a low nanoparticle size in a close range, high percentage of entrapment efficiency and drug loading, uniform prolonged release rate, and higher antibacterial activity against the EC04 clinical isolate.

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PURPOSE: The aim of this work is to optimize a polyethylene glycolated (PEGylated) polymer-lipid hybrid nanoparticulate system for the delivery of anastrozole (ANS) to enhance its biopharmaceutical attributes and overall efficacy. METHODS: ANS loaded PEGylated polymer-lipid hybrid nanoparticles (PLNPs) were prepared by a direct emulsification solvent evaporation method. The physical incorporation of PEG was optimized using variable ratios. The produced particles were evaluated to discern their particle size and shape, zeta-potential, entrapment efficiency, and physical stability. The drug-release profiles were studied, and the kinetic model was analyzed. The anticancer activity of the ANS PLNPs on estrogen-positive breast cancer cell lines was determined using flow cytometry. RESULTS: The prepared ANS-PLNPs showed particle sizes in the range of 193.6 ± 2.9 to 218.2 ± 1.9 nm, with good particle size uniformity (i.e., poly-dispersity index of around 0.1). Furthermore, they exhibited relatively low zeta-potential values ranging from -0.50 ± 0.52 to 6.01 ± 4.74. The transmission electron microscopy images showed spherical shape of ANS-PLNPs and the compliance with the sizes were revealed by light scattering. The differential scanning calorimetry DSC patterns of the ANS PLNPs revealed a disappearance of the characteristic sharp melting peak of pure ANS, supporting the incorporation of the drug into the polymeric matrices of the nanoparticles. Flow cytometry showed the apoptosis of MCF-7 cell lines in the presence of ANS-PLNPs. CONCLUSION: PEGylated polymeric nanoparticles presented a stable encapsulated system with which to incorporate an anticancer drug (ANS) with a high percentage of entrapment efficiency (around 80%), good size uniformity, and induction of apoptosis in MCF-7 cells.