Microencapsulated Solid Lipid Nanoparticles as a Hybrid Platform for Pulmonary Antibiotic Delivery

Abstract

Solid lipid nanoparticles (SLN) containing rifabutin (RFB), with pulmonary administration purposes, were developed through a technique that avoids the use of organic solvents or sonication. To facilitate their pulmonary delivery, the RFB-loaded SLN were included in microspheres of appropriate size using suitable excipients (mannitol and trehalose) through a spray-drying technique. Confocal analysis microscopy showed that microspheres are spherical and that SLN are efficiently microencapsulated and homogeneously distributed throughout the microsphere matrices. The aerodynamic diameters observed an optimal distribution for reaching the alveolar region. The dry powder's performance during aerosolization and the in vitro drug deposition were tested using a twin-impinger approach, which confirmed that the microspheres can reach the deep lung. Isothermal titration calorimetry revealed that SLN have higher affinity for mannitol than for trehalose. Upon microsphere dissolution in aqueous media, SLN were readily recovered, maintaining their physicochemical properties. When these dry powders reach the deep lung, microspheres are expected to readily dissolve, delivering the SLN which, in turn, will release RFB. The in vivo biodistribution of microencapsulated RFB-SLN demonstrated that the antibiotic achieved the tested organs 15 and 30 min post pulmonary administration. Their antimycobacterial activity was also evaluated in a murine model of infection with a Mycobacterium tuberculosis strain H37Rv resulting in an enhancement of activity against M. tuberculosis infection compared to nontreated animals. These results suggest that RFB-SLN microencapsulation is a promising approach for the treatment of tuberculosis.

Evaluation of stability and in vitro wound healing potential of melatonin loaded (lipid enriched) chitosan based microspheres

“…MCP had lower initial moisture content compared to MLCP (Table II), which could be explained by higher inlet temperature employed (145 °C vs. 110 °C, respectively) during spray drying. Higher inlet temperature resulted in higher outlet temperature and consequent lower moisture content of the MCP microspheres at the end of the drying process (21). However, upon storage, moisture content of MCP increased by ~20 % for samples kept at 5 °C and by ~40 % for samples kept at 25 °C/60 % RH.…”

“…There are some literature reports on the stability of spray-dried chitosan-based powders (19,20). However, although the conversion of lipid particles to dry powder via spray drying has been evaluated by other researchers (21,22), stability assessment of the lipid component and the dry powder over time is scarce (23). Stability testing was performed during a six-month period under two conditions: refrigerated (5 ± 3 °C) and at room temperature (25 ± 2 °C/60 ± 5 % RH).…”

Multifunctional Nanocarriers for Lung Drug Delivery

“…An in vivo test in a murine model of infection (Mycobacterium tuberculosis strain H37Rv) demonstrated that the inhalation of the dry powder permitted the effective delivery of the antibiotic to the lung, along with drug distribution to liver and spleen. Moreover, an enhancement of antibacterial activity was observed compared to nontreated animals [43]. Another formulation of SLN, this time composed of palmitic acid and cholesteryl myristate and loaded with rifampicin (~400 nm), was further freeze-dried to obtain an inhalable powder.…”

“…The specific features of the carriers will be outlined and the achieved outcomes described. The envisaged applications of the nanocarriers in lung delivery are diverse, but particularly address the delivery of proteins or protein-based materials, either for local or systemic effect [39,40], cancer treatment [41,42] and local delivery of antibiotics [43,44]. Therefore, the review will specifically focus on these topics.…”

Novel drug delivery systems and significance in respiratory diseases

“…Thus this SLN-based formulation can further be evaluated for its potential for targeted delivery, reduced dose, and dose frequency along with reduced side effects. SLNs loaded with rifabutin were encapsulated in microspheres using spray-drying method to enhance their stability and suitability for pulmonary administration in the form of dry powder inhaler in the study performed by Gaspar et al [38] . In vivo studies performed in mice presented that DPI-based delivery of antibiotic-loaded SLNs to the lungs was efficient, although a relevant amount of drug was recovered from the spleen and liver.…”