ABSTRACT
Designing a unique theranostic biocompatible, biodegradable, and cost-effective agent which is easy to be synthesized as a biohybrid material was the aim of this study. In this matter, asparagine attached to anionic linear globular dendrimer G2 (as a biocompatible, biodegradable, and cost-effective agent which is negatively charged nanosized and water soluble polymer that outweighs other traditionally used dendrimers) and finally contrast agent (Gd3+) was loaded (which made complexes) in synthesized asparagine-dendrimer. Observations revealed that, in addition to successful colon cancer and brain targeting, Gd3+-dendrimer-asparagine, the proposed theranostic agent, could increase T1 MR relaxation times, decrease T2 MR relaxation times significantly, and improve contrast of image as well as illustrating good cellular uptake based on florescent microscopy/flow cytometry and ICP-mass data. In addition to that, it increased tumor growth inhibition percentage (TGI%) significantly compared to FDA approved contrast agent, Magnevist. Totally, Gd3+-anionic linear globular dendrimer G2-asparagine could be introduced to the cancer imaging/therapy (theranostics) protocols after in vivo MR and fluorescent analysis and passing clinical trials. Hence, this nanotheranostic agent would be a promising candidate for brain drug delivery and imaging in the future.
Subject(s)
Dendrimers/chemistry , Theranostic Nanomedicine/methods , Animals , Asparagine , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/therapy , Contrast Media , Dendrimers/therapeutic use , Drug Design , Female , Gadolinium , Heterografts , Humans , Magnetic Resonance Imaging/methods , MiceABSTRACT
Tumor and especially breast cancer is among the most common causes of death worldwide. Finding novel nanosized therapeutic compounds have important role to decrease the chance of death and increase the survival. Cancer cells are highly attractive to glucose [with a nanosize bimolecular structure 1nm] as an energy source more than normal cell and nanosized therapeutics due to possessing different pharmacokinetic and pharmacodynamic have advantageous over classical dosage forms in cancer therapy. The aim of the study was to synthesize Glucosamin-Porphyrin-Tamoxifen [TPG] nanosized complex as a novel selective biocompatible anti breast cancer agent. After the synthesis procedure, this complex was purified and then tested In Vitro on breast cancer cells [MCF-7] in the absence or presence of the red light and found totally successful. The results showed a good anti breast cancer activity mediated by the activation of TNF-α and necrosis/apoptosis pathways for the nanosized complex with no alteration effects on blood PT/APTT and glucose or hexokinase levels/ activity. TPG nanoconjugate seems to be very good opponents to current anti breast cancer drugs and needs to be further investigated in near future.
Subject(s)
Antineoplastic Agents/chemistry , Breast Neoplasms/drug therapy , Glucosamine/analogs & derivatives , Glucose/chemistry , Nanoparticles , Porphyrins/chemistry , Porphyrins/chemical synthesis , Tamoxifen/analogs & derivatives , Tamoxifen/chemistry , Tamoxifen/chemical synthesis , Antineoplastic Agents/pharmacology , Apoptosis , Cell Line, Tumor , Female , Glucosamine/chemical synthesis , Glucosamine/chemistry , Glucosamine/pharmacology , Humans , Porphyrins/pharmacology , Tamoxifen/pharmacologyABSTRACT
The objective of the present study was to formulate naproxen-eudragit RS100 nanoparticles and investigate the physicochemical characteristics of the prepared nanoparticles. The nanoparticles of naproxen with eudragit RS100 were formulated using the solvent evaporation/extraction technique (the single emulsion technique). The effect of several process parameters, i.e., drug/polymer ratio, aqueous phase volume and speed of homogenization were considered on the size of the nanoformulations. The physicochemical characteristics of nanoparticles were studied applying particle size analysis, differential scanning calorimetry, X-ray crystallography, Fourier transform infrared spectroscopy and scanning electron microscopy. The release rate of naproxen from various drug/polymer nanoparticles was investigated as well. All the prepared formulations using eudragit RS100 resulted in nano-range size particles with relative spherical smooth morphology. The nanoparticles of naproxen-eudragit RS100 displayed lower crystallinity. The intermolecular interaction between naproxen and eudragit RS100 was detected in the FT-IR spectrum of the nanoparticles. All the nanoparticles displayed a slowed release pattern with the reduced burst release in comparison with the intact drug powder and physical mixtures of drug and polymer. According of these findings, formulation of the naproxen-eudragit RS100 nanoparticles was able to improve the physicochemical characteristics of the drug and possibly will increase the anti-inflammatory effects of drug following its ocular or intra-joint administration.
