Stimuli sensitive hybrid nanoparticles have been synthesized using a layer-by-layer technique and demonstrated for dual chemo-photothermal destruction of breast cancer cells. The hybrid nanoparticles are composed of alternating layers of graphene oxide and graphene oxide conjugated poly-l-lysine coating the surface of a thermosensitive cationic liposome containing doxorubicin as a core. Data suggests that the hybrid nanoparticles may offer many advantages for chemo-photothermal therapy. Advantages include a decrease of the initial burst release which may result in the reduction in systemic toxicity, increase in pH responsivity around the tumor environment and improved NIR light absorption.

The challenge of eliminating Pseudomonas aeruginosa infections, such as in cystic fibrosis lungs, remains unchanged due to the rapid development of antibiotic resistance. Poor drug penetration into dense P. aeruginosa biofilms plays a vital role in ineffective clearance of the infection. Thus, the current antibiotic therapy against P. aeruginosa biofilms need to be revisited and alternative antibiofilm strategies need to be invented. Fungal quorum sensing molecule (QSM), farnesol, appears to have detrimental effects on P. aeruginosa. Thus, this study aimed to codeliver naturally occurring QSM farnesol, with the antibiotic ciprofloxacin as a liposomal formulation to eradicate P. aeruginosa biofilms. Four different liposomes (with ciprofloxacin and farnesol, Lcip+far; with ciprofloxacin, Lcip; with farnesol, Lfar; control, Lcon) were prepared using dehydration-rehydration method and characterized. Drug entrapment and release were evaluated by spectrometry and high performance liquid chromatography (HPLC). The efficacy of liposomes was assessed using standard biofilm assay. Liposome-treated 24 h P. aeruginosa biofilms were quantitatively assessed by XTT reduction assay and crystal violet assay, and qualitatively by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). Ciprofloxacin release from liposomes was higher when encapsulated with farnesol (Lcip+far) compared to Lcip (3.06% vs 1.48%), whereas farnesol release was lower when encapsulated with ciprofloxacin (Lcip+far) compared to Lfar (1.81% vs 4.75%). The biofilm metabolism was significantly lower when treated with Lcip+far or Lcip compared to free ciprofloxacin (XTT, P < 0.05). When administered as Lcip+far, the ciprofloxacin concentration required to achieve similar biofilm inhibition was 125-fold or 10-fold lower compared to free ciprofloxacin or Lcip, respectively (P < 0.05). CLSM and TEM confirmed predominant biofilm disruption, greater dead cell ratio, and increased depth of biofilm killing when treated with Lcip+far compared to other liposomal preparations. Thus, codelivery of farnesol and ciprofloxacin is likely to be a promising approach to battle antibiotic resistant P. aeruginosa biofilms by enhancing biofilm killing at significantly lower antibiotic doses.

Capsule-based dry powder inhalers (cDPIs) are widely utilized in the delivery of pharmaceutical powders to the lungs. In these systems, the fundamental nature of the interactions between the drug/formulation powder, the capsules, the inhaler device, and the patient must be fully elucidated in order to develop robust manufacturing procedures and provide reproducible lung deposition of the drug payload. Though many commercially available DPIs utilize a capsule-based dose metering system, an in-depth analysis of the critical factors associated with the use of the capsule component has not yet been performed. This review is intended to provide information on critical factors to be considered for the application of a quality by design (QbD) approach for cDPI development. The quality target product profile (QTPP) defines the critical quality attributes (CQAs) which need to be understood to define the critical material attributes (CMA) and critical process parameters (CPP) for cDPI development as well as manufacturing and control.

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Dry powder inhalers are a diverse family of devices that have emerged as a rapidly growing segment of the respiratory therapeutics area. The forces that these devices must impart into dry powder formulations for effective dispersion performance and reproducibility of delivery are relatively large, and multiple mechanisms have been developed in attempts to improve the efficiency of these systems. In this review, we address the reasons for the proliferation of dry powder inhalers, beginning with an abbreviated introduction on the basic inter-particulate forces that need to be disrupted to achieve successful powder dispersion and effective lung delivery. From this background, we survey the diversity of inhaler designs, starting from marketed devices, before introducing some of the novel device designs under development, both patient driven (passive) and device driven (active), as we attempt to link the themes of the device design features to the present understanding of the dynamics governing powder dispersion. Finally, we conclude by providing some assessment on the future of the wide range of device designs and mechanisms that have evolved by considering technical, regulatory and market forces.