Targeted DPPC/DMPG surface-modified voriconazole lipid nanoparticles control invasive pulmonary aspergillosis in immunocompromised population: in-vitro and in-vivo assessment.

Invasive pulmonary aspergillosis (IPA) is the most devastating Aspergillus-related lung disease. Voriconazole (VRZ) is the first-line treatment against IPA. Despite availability in oral and parenteral dosage forms, risks of systemic toxicity dictate alternative pulmonary administration. Inspired by natural lung surfactants, dipalmitoylphosphatidylcholine/dimyristoylphosphatidylglycerol (DPPC/DMPG) surface-modified lipid nanoparticles (LNPs) were scrutinized for pulmonary administration. DPPC/DMPG-VRZ-LNPs prepared using ultrasonication/thin film hydration were investigated for colloidal properties over 3-month shelf storage. They were stable with a slight change in entrapment efficiency. They provided a sustained VRZ release over 24 h, with a rapid initial release. In vitro aerosolization indicated higher percentages of VRZ deposited on stages corresponding to secondary bronchi and alveolar ducts. Moreover, intrapulmonary administration maintained high lung VRZ concentration (27 ± 1.14 µg/g) after 6 h. A preclinical study using a cyclophosphamide-induced neutropenic rat model demonstrated a 3-fold reduction in BALF-Galactomannan down to 0.515 ± 0.22 µg/L confirming DPPC/DMPG-VRZ-LNPs potential in hyphal growth inhibition. Histopathological examination of infected/nontreated lung sections exhibited dense fungal load inside alveoli and blood vessels indicating massive tissue and angio-invasiveness. Nevertheless, DPPC/DMPG-VRZ-LNPs-treated animals displayed minimal hyphae with no signs of invasiveness. The developed bioinspired nanoparticles serve as prospective bioactive nanocarrier candidates for pulmonary administration of VRZ in the management of IPA.

Gelucire-Based Nanoparticles for Curcumin Targeting to Oral Mucosa: Preparation, Characterization, and Antimicrobial Activity Assessment.

The purpose of the study was to prepare and characterize curcumin (Cur) solid lipid nanoparticles (CurSLN) with a high-loading capacity and chemical stability for the treatment of oral mucosal infection. CurSLN were formulated using different lipids, namely, Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and poloxamer 407 as a surfactant. Formulae were evaluated for their entrapment efficiency, particle size, and ex vivo mucoadhesion test. Microbiological evaluation was carried out on six microorganisms, five of which are the most commonly affecting oral cavity in terms of determination of minimum inhibitory concentration (MIC), and minimum bactericidal concentration. Transmission electron microscopy was conducted for ultrathin section for Candida albicans-treated with formulated Cur. The results showed high entrapment efficiency and stability enhancement for Cur powder. Significant amount of Cur was retained onto the mucosal tissue indicating preferential mucosal uptake. CurSLN showed higher antimicrobial activity as compared with Cur raw material and chemically stabilized Cur where it showed MIC (0.185, 0.09375, 0.75, 3, 1.5, and 0.1875 mg/mL) against Staphylococcus aureus, Streptococcus mutans, Viridansstrept, Escherichia coli, Lactobacillus acidophilus, and Candida albicans, respectively. The prepared lipid nanoparticles maintained Cur chemical stability and microbiological activity. The lack of local antimicrobial therapeutics with minimum side effects augments the importance of studying natural products for this purpose.