compose to ND-mediated DOX retention in tumor cells

compose with NDs, theaqueous dispersibility of purvalanol A and 4-hydroxytamoxifen was improved markedly204. By adsorbing the drug on the surfaces,NDs greatlydecrease the particle size and increased the zeta potential of thesedrugs in water, develop their dispersibility and potentially cellularuptake. Alike to the previous studies, the NDs protect the therapeuticactivity of the drugs, as demonstrated by DNA fragmentation and3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay for ND-4-hydroxytamoxifen and ND-purvalanol A composites,respectively. These discovery proposed that NDs can play an important rolein designing injectable formulations of water-insolubledrugs. The efficacy of NDs to deliver chemotherapeutic drugs was examinedrecently in animal models for the first time202. In addition to generalized toxicity,large particle size and poor water solubility, chemotherapeutic drugs alsotrigger acquired and intrinsic chemoresistance in tumor cells.

 Amongdifferent factors, overexpression of P-glycoprotein on the cellular membranes, producepremature efflux of the drug from cells, is the leading cause for thedevelopment of chemoresistance in mammalian tumor cells. This challenge couldbe addressed by using a delivery system that not only improve the uptake of thechemotherapeutic drugs but also keep them in the cancer cells for a longerperiod. The study revealed that DOX bound to the ND surface was importantlymore toxic towards DOX-resistant mouse LT2-Myc liver and 4T1 mammary tumor models than bare DOX. The highchemotherapeutic efficacy of the ND-DOX compound was assigned to ND-mediatedDOX retention in tumor cells asdetermined by fluorescence microscopy and quantitative analysis205. Furthermore, long-term treatmentshow the superiority of the DOX bound to ND over the bare DOX in preventingtumor growth. NDs not only circumvented the premature efflux of DOX fromtumor cells but also enhance the adverse effects of naked DOX by appreciablyreducing the myelosuppression and early mortality. Morever, NDs increasedthe circulation halftime of DOX from 0.

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83to 8.43 hours, which further demonstrate their sequestering behavior proposedin earlier studies. The potential of NDs as a targeted protein-delivery vehiclewas estimated in a pH-dependent system. By means of physical adsorption, NDsattain greatly high surface loading of bovine insulin (~80%) in pH-neutralwater at a weight ratio of 1:4 of insulin:NDs.       Alike to the previous study, theaggregation characteristics (size, zeta potential and polydispersity index) ofthe insulin modified after interacting with NDs206.

This proposed that NDshave the ability to promote uniform-sized complex formation. Further, theliberation of insulin from the surface of the NDs was almost 20 times higherat  pH of 10.5 as compared to neutral pHmedium. The applicability of ND-bound insulin was evidenced by MTT assayin serum-starved murine macrophages. A higher cellular viability wasobserved with sodium hydroxide-treated ND-insulin than with neutral pH-treatedND-insulin.

Same results were obtained by estimating the gene expression ofinsulin 1 and granulocyte colony stimulating factor in serum-starved mouseadipocytes. Hence, formulations of insulin can be designed with NDs totarget the recovery of injured tissues that have a basic pH due tobacterial growth.  Although there iscompelling evidence to support the utilization of NDs as drug delivery agentsfor small molecules, their potential as gene delivery vectors has been lessbroadly explored.

The major drawback to use the naked nucleic acids astherapeutics is their incapable cellular delivery15. Physicochemicalproperties such as high negative surface charge and large molecular weight arebarriers in the efficient cellular internalization of the DNA and smallinterfering RNA (siRNA). While DNA is too large for cellular uptake, therelatively small size of siRNA also cause an additional challenge to itscellular delivery, as particles having a molecular weight of less than 50 kDaare adaptable to excretion through glomerular filtration. Athours  examined the NDs as a platform to produced theenhanced plasmid DNA (pDNA) delivery systems.  At first, they coated NDswith polyethyleneimine 800 (PEI800) then allowed to interact with luciferase pDNA via electrostatic forces. NDs werefound to improve the transfection efficiency of the polymer by 70-fold at a15:1 weight ratio of ND-PEI800:pDNA in HeLa cells, which might be due toND-mediated cellular and nuclear uptake of the pDNA206.

 Alike to DNAdelivery, the ND-based complex (ND-PEI800) was used to deliver anti-greenfluorescent protein siRNA to breast cancer cells indicating green fluorescent