The present study suggests that PEG-PGA-co-PDL-PEG and PGA-co-PDL-PEGme could be considered as alternative novel biodegradable sustained release carriers for lung delivery. They showed an enhanced encapsulation efficiency and lower hydrophobicity. Furthermore, they have the ability to enhance the release of SD from the prepared microparticles compared to PGA-co-PDL microparticles. Utilizing lipase enzyme from Candida antarctica successfully produced the PEG and mPEG containing polymers within higher yields and lower surface contact angle (θ) compared to PGA-co-PDL hence, an optimum deposition on lung periphery was obtained from NGI data. In addition, incorporation of l-leucine was found to enhance the aerosolization performance and decrease the continuous release of SD from different used carriers. PGA-co-PDL-PEGme has the ability to deliver higher amounts of SD to the central and peripheral regions of the lungs. Furthermore, cell viability study revealed the safety of PEG-PGA-co-PDL-PEG and PGA-co-PDL-PEGme spray dried microparticles. Future studies will be conducted to determine if the polymers elicit an immune response and the drug transport through different lung cell lines e.g., calu-3 cell lines. In addition, we will investigate the possibility of making nanoparticles to enhance the aerosolization performance and interaction with the lung cells.
Mucositis is the enba of the mucous membrane coating the digestive tract. When it involves the mucous membrane of the oral and oropharyngeal regions, it is termed as oral mucositis (OM). OM is a major problem for cancer patients receiving head and neck radiotherapy, stem cell transplantation and myelosuppressive chemotherapy for solid tumors (Raber-Durlacher et al., 2010). It is characterized by the atrophy and ulceration of squamous epithelial cells, vascular tissue damage and infiltration of inflammatory lymphocytes to the basement region (Sonis, 1998). This injury occurs as a consequence of chemotherapy (CT) and radiotherapy (RT), which are targeted to eliminate rapidly dividing cancer cells. While rapid celldivision is essential for maintaining a healthy oral mucosal epithelium,it is this normal function that renders the oral epithelium an unintendedtarget for CT and RT regimens, in cancer patients withhematologic malignancies undergoing hematopoietic stem cell transplantation (Pico et al., 1998).
Current treatments for oral mucositis in the clinical settings are local anesthetics, paliferin, glutamine, caphsol mouth rinse, amifostine and antimicrobial agents (Lionel et al., 2006; Yamamura et al., 1998). However, there are no established effective treatments for oral mucositis. Several animal models were developed for the induction of oral mucositis e.g., mouse lip (Parkins et al., 1983; Xu et al., 1984), mouse ventral tongue mucosa (Moses and Kummermehr, 1986) and hamster cheek pouch model (Sonis et al., 1990). Drawbacks of the aforementioned animal models were high mortality rate, un-intentional exposure of organs such as brain and disturbed mucous homeostasis (Bowen et al., 2011). In order to overcome the disadvantages, the present study was aimed at developing a simple and reliable model of oral mucositis in rats using chemotherapy and IR radiation.
Materials and methods
Mucositis is a common dose-limiting complication in patients receiving systemic anticancer chemotherapy, bone marrow transplantation, and local irradiation for tumors in the head and neck area (Raber-Durlacher et al., 2010). Oral mucosa comprises membranes with high mitotic index (rapid epithelial turnover and maturation rates). This renders the mucosa vulnerable to the adverse effects of chemotherapy and radiotherapy (Sonis, 1998).
A complex mechanism is involved in the pathophysiology of mucositis induced by chemotherapy and radiotherapy. Both chemotherapy and irradiation generate reactive oxygen species (ROS) which are deleterious to the DNA of epithelial cells. ROS may induce a cascade of biological events such as activation of transcription factors like nuclear factor-kappa B (NF-κB), which in turn result in the synthesis of various pro-inflammatory cytokines. These cytokines target epithelium, endothelium and connective tissue, thereby causing tissue injury. Chemotherapy and radiation also activate the apoptotic pathway, leading to mucosal disintegration. This exposes the nerve ends causing severe pain and bacterial infections (Sonis, 2004).