Controlled Release of Nor-β-lapachone by PLGA Microparticles: A Strategy for Improving Cytotoxicity against Prostate Cancer Cells

Abstract

Prostate cancer is one of the most common malignant tumors in males and it has become a major worldwide public health problem. This study characterizes the encapsulation of Nor-β-lapachone (NβL) in poly(D,L-lactide-co-glycolide) (PLGA) microcapsules and evaluates the cytotoxicity of the resulting drug-loaded system against metastatic prostate cancer cells. The microcapsules presented appropriate morphological features and the presence of drug molecules in the microcapsules was confirmed by different methods. Spherical microcapsules with a size range of 1.03˘0.46 µm were produced with an encapsulation efficiency of approximately 19%. Classical molecular dynamics calculations provided an estimate of the typical adsorption energies of NβL on PLGA. Finally, the cytotoxic activity of NβL against PC3M human prostate cancer cells was demonstrated to be significantly enhanced when delivered by PLGA microcapsules in comparison with the free drug.

Preparation and optimization of monodisperse polymeric microparticles using modified vibrating orifice aerosol generator for controlled delivery of letrozole in breast cancer therapy

“…From the in vitro drug release experiment, it is clearly shown that LTZ can gradually be released from the microparticles in a sustained fashion for 30 days, while the free LTZ reached the concentration plateau in 12 to 24 h. The sustained cytotoxicity of drug-loaded microparticles could be additionally attributed to the internalization of LTZloaded MDP into the cells and the successive drug release from microparticles inside the cells, enhancing the action of LTZ and preventing the short acute action of the drug. Similar findings regarding the uptake of Nor--lapachone-and Doxorubicin-PLGA loaded microparticles by treated cancer cells were previously reported [57,58,59]. Our results also indicated that our formulations were non-toxic to MEC normal breast epithelial cells at all concentrations expect for 100 µM, which indicates that these monodisperse polymeric formulations manufactured using the VOAG technology are potentially safe to noncancerous cells (Figure 9).…”

Advanced Routes in Synthesis and Reactions of Lawsone Molecules (2‐Hydroxynaphthalene‐1,4‐dione)

“…The reaction of 1 with aldehyde derivatives and 3‐substituted isoxazol‐5‐amine under microwave irradiation within short periods of 10–26 min in acetic acid yielded benzo[h]isoxazolo[5,4‐b]quinolin‐5,6‐dione derivatives 305 in yield 61–91% . Refluxing 1 with aromatic amine and aromatic aldehyde in the presence of indium(III) chloride (InCl 3 ) for 5.5–7 h or stirring at r.t. for 5 h afforded 2‐(arylr(arylamino)methyl)naphthalene‐1,4‐dione 306 in yield 70–91% (Scheme ).…”

“…Lawsonia alba Lam. ( L. alba ; HNQ) is locally known as henna or mehndi . HNQ was showed the presence of keto‐enol form that may be suitable for electrochemical receptor for anions such as CN − , AcO − , F − , and H 2 PO 4 − ions (Fig.…”

“…The quinone moiety forms the base of biological activity of a number of clinical and experimental drugs that are associated with antitumor , antimalarial, , antioxidant , anticancer , antiproliferarive agent , antitrypanosomiasis , antitopoisomerase , antiprotozoal , and antimicrobial studies (Fig. ).…”

NQO1 is Required for Beta-lapachone-mediated Downregulation of Breast Cancer Stem Cell Activity

“…Beta-lapachone (bL) is an o-naphthoquinone extracted from plants and has many pharmacological effects [14]. In the last decade, many studies to elucidate the effect of bL on cancer development have been conducted and have shown that bL has an inhibitory effect on various cancers such as epidermoid laryngeal cancer [15] and prostate [16][17][18][19], colon [20,21], ovarian [19], lung [22], and breast cancer [23]. bL has been identified to suppress cancer proliferation by directly interacting with and inhibiting the catalytic activity of DNA topoisomerase I [24], by inducing apoptosis or necrosis by releasing mitochondrial cytochrome C from mitochondria [25] and PARP cleavage [26,27], by blocking the lethal DNA damage repair (PLDR) system [28], by inducing G1/S cell cycle arrest [29], and by activating c-JUN NH2-terminal kinase [30] and caspases [31].…”