Polyacrylamide-punicic acid conjugate-based micelles for flutamide delivery in PC3 cells of prostate cancer: synthesis, characterisation and cytotoxicity studies.

The aim of the present study was to synthesize a novel biopolymeric micelle based on punicic acid (PA) and polyacrylamide (PAM) for carrying chemotherapeutic drugs used in prostate cancer treatment. A polymer composite micelle was prepared by chemical conjugation between PAM and PA. The micelles were prepared by self-assembly via film casting followed by ultrasonication method. The successful production of PAMPA copolymeric micelles was confirmed using FTIR, 1H-NMR, and TEM. Then, flutamide was loaded in the designed nanomicelles and they were characterized. The cell cytotoxicity of the micelles was studied on PC3 cells of prostate cancer. The prepared nanomicelles showed the particle size of 88 nm, PDI of 0.246, zeta potential of -9 mV, drug loading efficiency of 94.5%, drug release of 85.6% until 10 hours in pH 7.4 and CMC of 74.13 µg/ml. The cell viability in blank nanocarriers was about 70% in PC3 cells at concentration of 25 µM. More significant cytotoxic effects were seen for flutamide loaded micelles at this concentration compared to the free drug. The results suggest that the PAMPA co-polymeric nanomicelles can be utilized as an effective carrier to enhance the cytotoxic effects of flutamide in prostate cancer.

Folate-Targeted Polyacrylamide/Punicic Acid Nanomicelles for Flutamide Delivery in Prostate Cancer: Characterization, In Vitro Biological Evaluation, and its DFT Study.

BACKGROUND: Targeted nanocarriers can be used for reducing the unwanted side effects of drugs in non-target organs. Punicic acid, the polyunsaturated fatty acid of pomegranate seed oil, has been shown to possess anti-cancer effects on prostate cancer and the study also covers recent patents related to prostate cancer. The objective of the current study was to synthesize a co-polymeric micelle for delivery of Flutamide (FL) in prostate cancer using Polyacrylamide (PAM) and Punicic Acid (PA). METHODS: The co-polymer of PAM and PA was synthesized and conjugated to folic acid. The successful conjugation was studied computationally by the density functional theory method and was confirmed by the FT- IR and 1HNMR. The folate-PAMPA micelles produced by the film casting method were characterized physically. FL was loaded in the nanomicelles and its release test was done at different pH. The Critical Micelle Concentration (CMC) was measured by pyrene as a fluorescent probe. Their cellular uptake and cytotoxicity were evaluated on PC3 prostate cancer cells. The molecular geometry and vibrational frequencies of two different possibilities for conjugation were calculated using the B3LYP/6-31G basis set. RESULTS: The CMC of the micelles and their particle size were 79.05 µg/ml and 88 nm, respectively. The resulting nanocarriers of FL showed significantly more cytotoxic effects than the free drug at a concentration of 25 µM. The calculated results showed that the optimized geometries could well reproduce the structural parameters, and the theoretical vibrational frequencies were in good agreement with the experimental values. CONCLUSION: Folate-PAMPA nanomicelles may be promising for the enhancement of FL cytotoxicity and seem to potentiate the effect of chemotherapeutic agents used in prostate cancer treatment.

Acid-functionalized Mesoporous Silicate (KIT-5-Pr-SO3H) Synthesized as an Efficient and Nanocatalyst for Green Multicomponent.

AIM AND OBJECTIVE: KIT-5 nanoporous silica was functionalized with sulfonic acid and SO3H group has been immobilized on nanoporous KIT-5 silica support via in situ method to produce novel nanocatalyst as "KIT-5-Pr-SO3H". The catalyst was fully characterized by FT-IR, SEM, EDXs, TEM, BET and TGA techniques. The surface morphology images approved that the nanocatalyst particle sizes are around 7-15 nm. The prepared catalyst was efficiently used in the synthesis of benzimidazolo quinazolinones, imidazo[1,2- a]chromeno[4,3-d]pyrimidinone and imidazo[1,2-a]pyrimidine via a multicomponent reaction under green conditions. The easy synthesis condition, environmental compatibility, high specific surface area, reusability for 5 run without loses in any activity, high selectivity, availability of raw material, are the remarkable properties for this new catalyst. MATERIALS AND METHODS: All reagents were purchased from Aldrich and Merck with high-grade quality and used as received. The structural characteristics of the KIT-5 which was obtained, using three-dimensional large cage type face-centered cubic Fm3m mesoporous silica materials (KIT-5) nanocages were obtained according to the procedure described by Kleitz et al. Results: The purpose of this study is developing a new acid-functionalized mesoporous catalyst. Initially, (KIT-5) nanocages were obtained according to the procedure described by Kleitz et al. Then, KIT-5-Pr-SH was prepared by Mercaptopropyltriethoxysilane as illustrated in Scheme 1. In the next step, the solid product was oxidized with H2O2. The full characterization for proving the structure of the nano-size particles was achieved using FT-IR, TGA, TEM, SEM, and EDX analysis. CONCLUSION: Acid-functionalized mesoporous silica has been proved to act as an effective catalyst in various organic reactions. In this project, for the first time, KIT-5 was functionalized by propyl-sulfonic acid as a heterogeneous solid acid catalyst. Sulfonic acid functionalized KIT-5 (KIT-5-Pr-SO3H) performs as an organicinorganic hybrid catalyst, whereas Brønsted acid sites have been selectively generated. In this regard, the catalytic activities of this novel heterogeneous catalyst were successfully examined by the one-pot multicomponent reaction.

Synthesis, in vitro characterization, and anti-tumor effects of novel polystyrene-poly(amide-ether-ester-imide) co-polymeric micelles for delivery of docetaxel in breast cancer in Balb/C mice.

OBJECTIVE: The goal of the present work was to make novel co-polymeric micellar carriers for the delivery of docetaxel (DTX). SIGNIFICANCE: Co-polymeric micelles can not only solubilize DTX and eliminate the need for toxic surfactants to dissolve it, but also cause passive targeting of the drug to the tumor and reduce its toxic side effects. METHODS: Poly(styrene-maleic acid) (SMA) was conjugated to poly (amide-ether-ester-imide)-poly ethylene glycol (PAEEI-PEG). Copolymer synthesis was proven by Fourier transform infrared (FTIR) and 1H-nuclear magnetic resonance (1H-NMR). The SMA-PAEEI-PEG micelles loaded with DTX were prepared and their critical micelle concentration (CMC), zeta potential, particle size, entrapment efficiency, and their release efficiency were studied. MCF-7 and MDA-MB231 breast cancer cells were used to evaluate the cellular uptake and cytotoxicity of the micelles. The antitumor activity of the DTX-loaded nanomicelles was measured in Balb/c mice. RESULTS: The FTIR and HNMR spectroscopy confirmed successful conjugation of SMA and PAEEI-PEG. The drug loading efficiency was in the range of 34.01-72.75% and drug release lasted for 120 h. The CMC value of the micelles was affected by the SMA/PAEEI-PEG ratio and was in the range of 29.85-14.28 µg/ml. The DTX-loaded micelles showed five times more cytotoxicity than the free drug. The DTX loaded micelles were more effective in tumor growth suppression in vivo and the animals showed an enhanced rate of survival. CONCLUSION: The results show that the SMA-PAEEI-PEG micelles of DTX could potentially provide a suitable parenteral formulation with more stability, higher cytotoxicity, and improved antitumor activity.