The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems.
The current study aimed at preparing AgNPs and three different core-shell silver/polymeric NPs composed of Ag core and three different polymeric shells: polyvinyl alcohol (PVA), polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP). Thereafter, the core/shell NPs were loaded with a chemotherapeutic agent doxorubicin (DOX). Finally, the cytotoxic effects of the different core-shell Ag/polymeric NPs-based combinatorial therapeutics were tested in-vitro against breast cancer (MCF-7) and human fibroblast (1BR hTERT) cell lines. AgNPs, Ag/PVA and Ag/PVP NPs were more cytotoxic to MCF-7 cells than normal fibroblasts, as well as DOX-Ag, DOX-Ag/PVA, DOX-Ag/PEG and DOX-Ag/PVP nanocarriers (NCs). Notably, low dosage of core-shell DOX-loaded Ag/polymeric nanocarriers (NCs) exhibited a synergic anticancer activity, with DOX-Ag/PVP being the most cytotoxic. We believe that the prepared NPs-based combinatorial therapy showed a significant enhanced cytotoxic effect against breast cancer cells. Future studies on NPs-based combinatorial therapy may aid in formulating a novel and more effective cancer therapeutics.
Polyelectrolyte capsules made of different biodegradable and nonbiodegradable polymers can be designed as systems for effective encapsulation and delivery of compounds. The objective of this work was to synthesize biocompatible and biodegradable capsules (<1 μm) by the layer-by-layer (LbL) approach using alginate (ALGI) and poly-L-arginine (PARG) polyelectrolytes with a pH-sensitive outer layer of EUDRAGIT L 100 (EuL) polymer. Those capsules were loaded with curcumin as a model therapeutic drug, which possesses antioxidant, anti-inflammatory, and anticancer activity. Encapsulation of drugs inside capsules protects its therapeutic activity and increases its bioavailability. We report the capsule stability, loading efficiency, drug release, as well as capsule degradation studies as a function of pH. Furthermore, in vitro biocompatibility studies of capsules including cell viability and uptake studies were performed using HeLa cells. The here synthesized capsules exhibited good reproducibility, spherical shape, and high monodispersibility. The capsules showed good loading efficiency and drug release profile dependent upon pH environment. The in vitro studies indicate that the capsules exhibited acceptable biocompatibility and are highly internalized by cells. Our study thus suggests that alginate LbL capsules could be used as an efficient drug carrier with effective encapsulation and successful in vitro release of cargo in the cell.
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