Pulmonary delivery of resveratrol-loaded nanocomposite microparticles to treat lung cancer
Abstract
Lung cancer was a rare disease in the latter part of the 19th century, but grew into a full-scale epidemic in the 20th century, becoming the most common cause of cancer related death worldwide. Current cancer chemotherapy, involves the administration of cytotoxic drugs that kill all cells exhibiting a high rate of proliferation and regeneration, which is a characteristic of cancer cells, but also non-cancerous cells, such as hair follicles, bone marrow and gastrointestinal tract cells. Therefore, the systemic delivery of chemotherapy leads to adverse effects, such as chemotherapy induced alopecia (CIA) and chemotherapy-induced peripheral neuropathy (CIPN), which can range from life-altering to life-threatening. Moreover, the economic impact of current cancer chemotherapy is unsustainable and, thus, an alternative therapy for lung cancer need to be investigated. Towards this goal, resveratrol loaded polymeric nanoparticles (NPs) formulated into nanocomposite microparticles (NCMPs) using L-leucine and chitosan were developed for the pulmonary delivery via dry powder inhalation. Resveratrol was loaded into NPs of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) with sizes ranging between 220-230 nm, which are ideal for uptake into cells. The 5%- and 10% resveratrol-loaded NPs (5% RNP and 10% RNP) had a high encapsulation efficiency of 39 ± 0.12 and 70 ± 0.89% and a drug loading of 78 ± 0.24 µg and 70 ± 0.89 µg (w/w), respectively. The PGA-co-PDL blank NPs (BNP) at 1…
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