Hisham Al-Obaidi

Ciprofloxacin (CFX) is a potent antibiotic for respiratory infections, but its poor solubility and high crystallinity limit its effectiveness in dry powder inhaler (DPI) delivery. Although soluble forms such as CFX hydrochloride are available, their rapid dissolution may lead to systemic absorption, undermining localized lung targeting. To address this, we developed solid dispersions of CFX with primary bile acids, namely, cholic acid (CA) and chenodeoxycholic acid (CDA), using spray drying and ball milling to enhance solubility in a controlled manner while maintaining deposition in the lungs. Differential scanning calorimetry showed glass-transition temperature (T_g) values were elevated for both bile acids, with CA dispersions showing slightly higher absolute values (114.16-131.77 °C vs 109.13-120.67 °C). However, Fourier transform infrared and dissolution data indicated that CDA formed stronger directional hydrogen bonding with CFX. X-ray diffraction confirmed partially amorphous dispersions with minimal residual crystallinity. Solubility enhancement was observed for both bile acids, showing slightly higher values with CA dispersions. Aerodynamic assessments using an Andersen cascade impactor revealed improved lung deposition with CFX-CDA, with a higher fine particle fraction (FPF: 30.81%) and lower mass median aerodynamic diameter (MMAD: 5.89 μm) compared to CFX-CA (FPF: 26.93%, MMAD: 6.19 μm). The emitted dose was highest in CDA with nearly 5 mg compared to CA dispersions (∼3 mg). In vitro antimicrobial studies showed that dispersions maintained comparable antimicrobial activity to pure CFX, while in vivo toxicology in rats indicated mild, dose-dependent hepatic changes. CDA formulations showed AST elevation at a low dose and ALP increase at a high dose, consistent with the known hepatic effects of this bile acid, while CA formulations were broadly comparable to pure CFX. Machine learning algorithms, including tree-based models and neural networks, were used to predict the formulation performance and identify critical variables. Feature selection was achieved using recursive elimination, and permutation analysis showed that the bile acid type, inlet temperature, and molar ratio were the most influential predictors of solubility and lung deposition. Models such as gradient boosting and elastic net showed a high predictive accuracy (R² > 0.85). Overall, this study highlights the potential of primary bile acid-based DPI formulations as effective inhalable antibiotic therapies.

This study aimed to develop microparticles of N-phenyl-2,2-dichloroacetamide (PDA), a chloramphenicol derivative with potential antibacterial and anticancer properties, to improve drug release and selectivity while reducing toxicity. PDA microparticles were prepared via spray-drying using L-leucine, Trehalose, and Mannitol. The particles were characterized for size, drug release, antibacterial activity, and cytotoxicity against A549 cancer cells and fibroblasts. PDA formulations exhibited controlled release and enhanced selectivity for cancer cells. S1 showed antibacterial activity against S. aureus. L-leucine formulations had reduced toxicity to normal fibroblasts. PDA microparticles offer potential as safer, targeted antibacterial and anticancer therapies, providing controlled release and reduced side effects.

This study aims to develop an innovative microencapsulation method for coated Polymyxin B, utilizing various polysaccharides such as hydroxypropyl β-cyclodextrin, alginate, and chitosan, implemented through a three-fluid nozzle (3FN) spray drying process. High-performance liquid chromatography (HPLC) analysis revealed that formulations with a high ratio of sugar cage, hydroxypropyl β-cyclodextrin (HPβCD), and sodium alginate (coded as ALG_HCD_HP_L^PM) resulted in a notable 16-fold increase in Polymyxin B recovery compared to chitosan microparticles. Morphological assessments using fluorescence labeling confirmed successful microparticle formation with core/shell structures. Alginate-based formulations exhibited distinct layers, while chitosan formulations showed uniform fluorescence throughout the microparticles. Focused beam reflectance and histograms from fluorescence microscopic measurements provided insights into physical size analysis, indicating consistent sizes of 6.8 ± 1.2 μm. Fourier-transform infrared (FTIR) spectra unveiled hydrogen bonding between Polymyxin B and other components within the microparticle structures. The drug release study showed sodium alginate's sustained release capability, reaching 26 ± 3% compared to 94 ± 3% from the free solution at the 24 h time point. Furthermore, the antimicrobial properties of the prepared microparticles against two Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, were investigated. The influence of various key excipients on the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values was evaluated. Results demonstrated effective bactericidal effects of ALG_HCD_HP_L^PM against both E. coli and P. aeruginosa. Additionally, the antibiofilm assay highlighted the potential efficacy of ALG_HCD_HP_L^PM against the biofilm viability of E. coli and P. aeruginosa, with concentrations ranging from 3.9 to 500 μg/m. This signifies a significant advancement in antimicrobial drug delivery systems, promising improved precision and efficacy in combating bacterial infections.

Lung diseases have received great attention in the past years because they contribute approximately one-third of the total global mortality. Pulmonary drug delivery is regarded as one of the most appealing routes to treat lung diseases. It addresses numerous drawbacks linked to traditional dosage forms. It presents notable features, such as, for example, a non-invasive route, localized lung drug delivery, low enzymatic activity, low drug degradation, higher patient compliance, and avoiding first-pass metabolism. Therefore, the pulmonary route is commonly explored for delivering drugs both locally and systemically. Inhalable nanocarrier powders, especially, lipid nanoparticle formulations, including solid-lipid and nanostructured-lipid nanocarriers, are attracting considerable interest in addressing respiratory diseases thanks to their significant advantages, including deep lung deposition, biocompatibility, biodegradability, mucoadhesion, and controlled drug released. Spray drying is a scalable, fast, and commercially viable technique to produce nanolipid powders. This review highlights the ideal criteria for inhalable spray-dried SLN and NLC powders for the pulmonary administration route. Additionally, the most promising inhalation devices, known as dry powder inhalers (DPIs) for the pulmonary delivery of nanolipid powder-based medications, and pulmonary applications of SLN and NLC powders for treating chronic lung conditions, are considered.