Synthesis and Biological Evaluation of Novel Folic Acid Receptor-Targeted, β-Cyclodextrin-Based Drug Complexes for Cancer Treatment

Drug targeting is an active area of research and nano-scaled drug delivery systems hold tremendous potential for the treatment of neoplasms. In this study, a novel cyclodextrin (CD)-based nanoparticle drug delivery system has been assembled and characterized for the therapy of folate receptor-positive [FR(+)] cancer. Water-soluble folic acid (FA)-conjugated CD carriers (FACDs) were successfully synthesized and their structures were confirmed by 1D/2D nuclear magnetic resonance (NMR), matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), and circular dichroism. Drug complexes of adamatane (Ada) and cytotoxic doxorubicin (Dox) with FACD were readily obtained by mixed solvent precipitation. The average size of FACD-Ada-Dox was 1.5–2.5 nm. The host-guest association constant Ka was 1,639 M−1 as determined by induced circular dichroism and the hydrophilicity of the FACDs was greatly enhanced compared to unmodified CD. Cellular uptake and FR binding competitive experiments demonstrated an efficient and preferentially targeted delivery of Dox into FR-positive tumor cells and a sustained drug release profile was seen in vitro. The delivery of Dox into FR(+) cancer cells via endocytosis was observed by confocal microscopy and drug uptake of the targeted nanoparticles was 8-fold greater than that of non-targeted drug complexes. Our docking results suggest that FA, FACD and FACD-Ada-Dox could bind human hedgehog interacting protein that contains a FR domain. Mouse cardiomyocytes as well as fibroblast treated with FACD-Ada-Dox had significantly lower levels of reactive oxygen species, with increased content of glutathione and glutathione peroxidase activity, indicating a reduced potential for Dox-induced cardiotoxicity. These results indicate that the targeted drug complex possesses high drug association and sustained drug release properties with good biocompatibility and physiological stability. The novel FA-conjugated β-CD based drug complex might be promising as an anti-tumor treatment for FR(+) cancer.

The relationship between spirituality, knowledge and tuberculosis (TB) medication adherence among African Americans and Haitians

Tuberculosis (TB) is an infectious disease and nonadherence to medication can lead to new cases, multi-drug resistant TB, or potential death. Additionally, healthcare professionals and individuals with TB’s knowledge of the disease and medication adherence are crucial for successful completion of medication therapy. Patient education is one of the most important aspects of care provided in healthcare settings (CDC, 1994). TB tends to disproportionately affect minority and economically disadvantaged patient populations. The purpose of this mixed method study was to explore the relationship between spirituality, knowledge, and TB medication adherence among African Americans and Haitians. The primary research question was: What is the relationship between spirituality, knowledge and TB medication adherence among African Americans and Haitians? Quantitative data were gathered from 33 questionnaires and analyzed by two ANOVAs and four chi square analyses. The null hypothesis was not rejected; there was not a statistically significant relationship between spirituality and TB medication adherence (p =.208) among the study’s African Americans and Haitians. Qualitative data concerning participants’ knowledge of TB, gathered from 16 individual interviews further informed this analysis. Secondary research questions examined the role of spirituality, knowledge of TB and medication adherence among African Americans and Haitians. Four common themes emerged across both groups to answer the secondary research questions. Interviews revealed the themes: (a) God is in control, (b) stigmatization of TB, (c) lack of knowledge, and (d) fear of death. The theme lack of knowledge about TB was found to contribute to stigmatization of TB patients. However, in this study stigma and lack of knowledge were related to initial denial of symptoms and delayed diagnosis, but not found to be related to TB medication adherence. This study could help adult educators and health educators enhance their educational interventions, develop a better understanding of adult learning, resulting in early diagnosis and treatment ultimately decreasing transmission of TB, drug resistance, and potential death. Educators should be aware that TB patients’ spirituality may be an important part of how they cope with having TB. A larger scale study, conducted at multiple locations should be conducted to extend the findings of this small scale exploratory study. Further studies should be done to better determine what patient, healthcare provider and health care system factors might mediate relationships that may exist between lack of knowledge of TB, stigma and TB medication adherence.