 buyer. That stated, if you negotiate properly you can get your rock at wholesale costs and after that have a jeweler style a setting. One final care: Most of these dealers just accept cold tough cash.
Every Sunday at 11am and 6.30pm, in the church.
The services usually last for around one hour. There is a children's talk given in the morning service. After this, children up to P5 leave for Sunday school and infants for creché. P6 to high schoolers sit together and take notes during the sermon and then meet together for their own fellowship after the service.
Vivek Mohrir, B.
Ebrahimi Shahmabadi, H.
This study aimed to evaluate the therapeutic efficacy of the cisplatin encapsulated into polybutylcyanoacrylate (PBCA) nanoparticles for the treatment of kidney cancer. The nanoformulation was successfully developed using the miniemulsion polymerization method and characterized in terms of size, size distribution, drug loading and encapsulation efficiencies, drug release behavior, in vitro cytotoxicity effects, in vivo toxicity, and therapeutic effects. Cisplatin-loaded PBCA nanoparticles were confirmed to be in nanoscale with the drug entrapment efficiency of 23% and controlled drug release profile, in which only 9% of the loaded drug was released after 48 h. The nanoparticles caused an increase in the cytotoxicity effects of cisplatin against renal cell adenocarcinoma cells (ACHN) (2.3-fold) and considerably decreased blood urea nitrogen and creatinine concentrations when compared to the standard cisplatin (1.6-fold and 1.5-fold, respectively). The nanoformulation also caused an increase in the therapeutic effects of cisplatin by 1.8-fold, in which a reduction in the mean tumor size was seen (3.5 mm vs. 6.5 mm) when compared to the standard cisplatin receiver rats. Overall, cisplatin-loaded PBCA nanoparticles can be considered as a promising drug candidate for the treatment of kidney cancer due to its potency to reduce the side effects of cisplatin and its toxicity and therapeutic effects on cancer-bearing Wistar rats.
Renal cell carcinoma (RCC; also known as renal adenocarcinoma), with increasing incidence, causes 90% of renal malignancies [1] and is responsible to 2.2% of all malignancies [2]. RCC is a highly metastasis malignancy [3] that 25–30% of RCC patients are diagnosed with metastasis [1]. Furthermore, it is one of the most lethal cancers with a five-year survival rate of 15–25% [4]. One study showed that nearly 270,000 new cases are diagnosed with RCC, which causes approximately 116,000 deaths worldwide [5]. Currently, chemotherapy is considered as a main approach for the treatment of kidney cancer [6], and cisplatin is one the chemotherapeutic agent used for the treatment of RCC [3].
Cisplatin plays a vital role in cancer treatment and has been widely used to treat various types of cancers, including ovarian, cervical, head and neck, and non-small-cell lung cancer for years [7]. It forms a cisplatin-DNA adduct, which causes cell death through the cell apoptotic process [8]. However, cisplatin has several severe side effects, including gastrotoxicity, ototoxicity, allergic reactions, and myelosuppression that limit its clinical use [9]. Today, nanoparticles are considered as a promising approach for improving the pharmacokinetics of various types of drugs [10,11].
Nanoparticles have been widely investigated as drug delivery systems to increase the therapeutic efficacy of drugs [12,13,14,15,16] and reduce their side effects [17,18]. Nanoparticles have a high surface area to volume ratio; therefore, they could encapsulate drugs in high concentrations and increase drug delivery to cancerous cells [19]. They are also considered as excellent drug delivery systems, due to isolating the chemotherapeutic compounds from the systemic environment and targeted accumulation of the compounds in solid tumors with leaky vasculature and impaired lymphatics, resulting in improved cellular uptake [20]. In addition, nanoparticles are able to increase the water solubility of small insoluble molecules, leading to improving their solubility and bioavailability [21]. Polybutylcyanoacrylate (PBCA) nanoparticles are polymeric carriers and have been broadly used for drug delivery purposes. They are biodegradable particles and potent to alter the biological distribution of therapeutic agents in the human body. Apart from this, PBCA nanoparticles take advantage of easy preparation and purification processes and being able to overcome multidrug resistance [22,23]. These features make these particles as a suitable candidate for drug delivery. The present study aimed to use this carrier for cisplatin delivery to RCC. For this purpose, the potency of PBCA as the cisplatin carrier was evaluated in vitro and in vivo environments for the treatment of kidney cancer. In this regard, the in vitro release behavior, cytotoxicity, in vivo toxicity, and therapeutic effects of the formulation were studied using the dialysis membrane method, 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and histopathological studies. Further analyses, including blood urea nitrogen (BUN) and creatinine concentrations, and their tumor size were also investigated to evaluate the toxicity of the nanoformulation.
Cisplatin-loaded PBCA nanoparticles were synthesized using miniemulsion polymerization method. In this method, dextran 70 kDa was used as a stabilizer to prevent macroaggregation of the nanoparticles [24]. Among various kinds of polyalkylcyanoacrylate nanoparticles, such as polymethyl, polyethyl, polypropyl, and polybutyl, PBCA has been commonly used for drug delivery, owning to its ability to interact with the different types of drugs [25]. Also, in cancer therapy, various studies have shown that PBCA nanoparticles are excellent carrier colloids for chemotherapeutic agents as they enhance the therapeutic effects of chemotherapeutics and reduce their side effects [9,26,27,28,29]. In the current study, honey and olive oil were used for stabilizing the nanoparticles. Researchers, in various studies, have also used these compounds to stabilize nanoparticles [30,31,32,33]. Moreover, honey and olive oil were used because of their surfactant activity and anticancer properties [23]. Surfactants inhibit nanoparticles’ aggregation through creating a physical barrier (a shell surrounding the particles) outside the particles [34,35]. In this study, the polymerization of BCA monomer was confirmed by the color change of the reaction medium from colorless to milky [22]. To confirm the monodispersity of the nanoparticles, dynamic light scattering (DLS) method was used, and the results showed that the nanoparticles were monodispersed (Figure 1).
The results also showed that cisplatin-loaded PBCA nanoparticles were formed in nanoscale size and with a negative zeta potential (Figure 1, Table 1). The size of nanoparticles is a critical factor in investigating the efficacy of loaded chemotherapeutics, in which smaller nanoparticles have higher cellular uptake and cellular transfection efficiency, resulting in a higher intracellular concentration of the loaded chemotherapeutics [36]. Particles with the size below 300 nm can efficiently enter target cells to exert the pharmaceutical function [37]. The size of cisplatin-loaded PBCA nanoparticles prepared in the present study was 274 ± 6.7 nm; thus, they can effectively enter the target cells. The zeta potential of the blank and cisplatin-loaded nanoparticles was found to be −7 ± 0.30 mV and −9 ± 0.42 mV, respectively. The colloidal stability of positive or negative charged nanoparticles is generally preserved in aqueous solutions with low ionic strength, due to the repulsive forces [38]. However, cisplatin-loaded PBCA nanoparticles showed more positive zeta potential compared to the PBCA nanoparticles. This is due to cisplatin has a positive charge [39], and it was loaded into the nanoparticles. Drug loading efficiency is a critical factor in polymeric carriers, for instance, low drug loading is responsible for both poor therapeutic efficacy and drug release profiles [40], resulting in the insufficient efficiency of drug delivery systems [41]. Therefore, improving drug loading efficiency is critical to achieving sufficient therapeutic activity [42]. This study showed that despite the low water solubility of cisplatin [43], drug loading efficiency of 23% was achieved. This confirmed that the miniemulsion polymerization method was efficient enough to prepare the nanoparticles. The shape and morphology of nanoparticles also play a critical role in the potency of nanoparticles as a drug delivery system, affecting the pharmacokinetics of the particles in the body [44]. In the current study, the morphology of the nanoparticles was precisely studied using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) (Figure 2). The SEM results showed that spherical monodisperse nanoparticles with the smooth surface and without surface fractures or pitting were formed (Figure 2A). The results of TEM confirmed the formation of spherical monodispersed cisplatin-loaded PBCA nanoparticles as solid nanoparticles (Figure 2B).
To evaluate the chemical structure of cisplatin and determine if it preserves its chemical structure, cisplatin-loaded PBCA nanoparticles were investigated using the Fourier-transform infrared (FTIR) spectrum. Changes in chemical structures of therapeutic compounds can change their biological activity [45]. In other words, chemical structure determines the biological properties of substances [46]. According to the results of the FTIR spectrum (Figure 3), the symmetric amine bending mode at 1290 cm−1 and the characteristic amine stretching mode at 3280 and 3200 cm−1 frequency regions appeared. According to these findings, which correspond to the FTIR spectrum of cisplatin [26,47], cisplatin remained intact in PBCA nanoparticles, i.e., cisplatin was loaded into the nanoparticles physically without forming any chemical bonds.
Drug delivery systems with a controlled release rate have substantial advantages compared to the conventional dosage forms. These systems (i) considerably decrease the dosing frequency and improve patient compliance, (ii) minimize the in vivo fluctuation of drug concentrations and maintain the drug