scholarly journals Multifunctional Nanobubbles Carrying Indocyanine Green and Paclitaxel for Molecular Imaging and the Treatment of Prostate Cancer

2020 ◽  
Author(s):  
Minmin Lan ◽  
Lianhua Zhu ◽  
Yixuan Wang ◽  
Dajia Shen ◽  
Kejing Fang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Indocyanine Green ◽  
Ultrasound Imaging ◽  
Multimodal Imaging ◽  
Photoacoustic Imaging ◽  
Drug Loading ◽  
Local Treatment ◽  
Therapeutic Effects ◽  
Tumour Xenografts

Abstract Background: Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and resolution, thereby enabling rapid, direct measurements and the tracking of tumour growth and metastasis. Moreover, ultrasound-targeted nanobubble destruction (UTND) provides an effective way to deliver drugs, effectively increasing the content of the drug in the tumour area and reducing potential side effects, thereby successfully contributing to the treatment of tumours. Results: In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs) and studied their applications in ultrasound imaging of prostate cancer as well as their therapeutic effects on prostate cancer when combined with UTND. ICG-PTX NBs were prepared by the mechanical oscillation method. The particle size and zeta potential of the ICG-PTX NBs were 469.5 ± 32.87 nm and -21.70 ± 1.22 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 6.2%, respectively. In vitro imaging experiments showed that ICG-PTX NBs were highly amenable to multimodal imaging, including ultrasound, photoacoustic and fluorescence imaging, and the imaging effect was positively correlated with their concentration. The imaging effects of tumour xenografts also indicated that ICG-PTX NBs were of good use for multimodal imaging. In experiments testing the growth of PC-3 cells in vitro and tumour xenografts in vivo, the ICG-PTX NBs+US group showed more significant inhibition of cell proliferation and the promotion of cell apoptosis compared to the other groups (P < 0.05). Blood biochemical analysis of the six groups showed that the levels of aspartate aminotransferase (AST), phenylalanine aminotransferase (ALT), serum creatinine (CRE) and blood urea nitrogen (BUN) in the ICG-PTX NBs and the ICG-PTX NBs+US groups were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organs showed no obvious abnormalities in the ICG-PTX NBs and the ICG-PTX NBs+US groups. Conclusions: ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent that can achieve multimodal imaging, including ultrasound, fluorescence and photoacoustic imaging, and can succeed in the local treatment of prostate cancer providing a potential novel method for integrated research on prostate cancer diagnosis and treatment.

scholarly journals Multifunctional Nanobubbles Carrying Indocyanine Green and Paclitaxel for Molecular Imaging and Treatment of Prostate Cancer

2020 ◽  
Author(s):  
Minmin Lan ◽  
Lianhua Zhu ◽  
Yixuan Wang ◽  
Dajia Shen ◽  
Kejing Fang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Indocyanine Green ◽  
Ultrasound Imaging ◽  
Multimodal Imaging ◽  
Photoacoustic Imaging ◽  
Drug Loading ◽  
Tissue Imaging ◽  
Tumor Xenografts

Abstract Background: Combining ultrasound imaging with photoacoustic imaging provides tissue imaging with high contrast and high resolution, thereby enabling rapid and direct measurement and tracking of tumor growth and metastasis. At the same time, ultrasound targeted nanobubble destruction (UTND) provides an effective way to drug accumulation; effectively increasing the content of the drug in the tumor area and reducing potential side effects, thereby contributing effectively to the treatment of the tumors.Result: In this study, we prepared multifunctional nanobubbles (NBs) carrying indocyanine green (ICG) and paclitaxel (PTX) (ICG-PTX NBs), and study their application in ultrasound imaging of prostate cancer as well as their therapeutic effect on prostate cancer when combined with ultrasound targeted nanobubble destruction (UTND). ICG-PTX NBs were prepared by mechanical oscillation method. Their particle size and Zeta potential of ICG-PTX NBs were 469.5±32.87 nm and -21.70±1.222 mV, respectively. The encapsulation efficiency and drug loading efficiency of ICG were 68% and 6.2%, respectively. In vitro imaging experiments showed that ICG-PTX NBs were highly amenable to multimodal imaging including ultrasound, photoacoustic and fluorescence imaging, and the imaging effect is positively correlated with their concentration. The imaging effect of tumor xenografts also indicated that ICG-PTX NBs were of good use for multimodal imaging. In experiments testing the growth of PC-3 cells in vitro and tumor xenografts in vivo, the ICG-PTX NBs+US group showed more significant inhibition of cell proliferation and promotion of cell apoptosis compared to the other groups (P < 0.05). Blood biochemical analysis of the six groups showed that the levels of aspartate aminotransferase (AST), phenylalanine aminotransferase (ALT), serum creatinine (CRE) and blood urea nitrogen (BUN) in the ICG-PTX NBs group and the ICG-PTX NBs+US group were significantly lower than those in the PTX group (P < 0.05). Moreover, H&E staining of tissue sections from vital organ showed no obvious abnormalities in the ICG-PTX NBs group and the ICG-PTX NBs+US group.Conclusions: ICG-PTX NBs can be used as a non-invasive, pro-apoptotic contrast agent for both diagnosis and treatment that can achieve enhanced imaging, effective inhibition and killing of prostate cancer under the guidance of multimodal imaging including ultrasound, fluorescence and photoacoustic imaging.

Minocycline hydrochloride loaded mPEG-PCLA membranes: Preparation and in vitro evaluation for periodontitis therapy

2021 ◽  
pp. 088391152199279
Author(s):  
Ningtao Wang ◽  
Zhengmei Huang ◽  
Shenchun Wang ◽  
Meidong Lang ◽  
Xiuyin Zhang
Keyword(s):  
Drug Delivery ◽  
Drug Loading ◽  
Membrane Surface ◽  
Local Treatment ◽  
In Vitro Release ◽  
Periodontal Pathogen ◽  
Antibacterial Drug ◽  
Periodontal Ligament Fibroblasts ◽  
Minocycline Hydrochloride

This study was aimed at alleviating shortcomings in the treatment of periodontitis by preparation of a biopolymer membrane loaded with minocycline hydrochloride (MH) inserted into periodontal pockets to treat infections. Monomethoxy-poly (ethylene glycol)-poly (ε-caprolactone-co-L-lactide) (mPEG-PCLA) is a biocompatible and biodegradable amphiphilic block copolymer. It, therefore, has attracted considerable attention in drug delivery systems and periodontal treatment. We chose it as a membrane material for MH-drug loading. The MH-loaded membranes were prepared by the solvent casting technique with the content of 5, 8 and 10 wt.%, respectively. Fourier transform infrared spectra (FTIR) revealed no interaction between MH and polymer. The drug-loaded membrane surface morphology was investigated by scanning electron microscopy (SEM). In vitro release studies showed that the initial drug release exceeded 40% within 24 h, followed by a sustained release for up to 2 weeks, which would enable the therapeutic level to maintain over a longer time. The antibacterial activity studies in vitro demonstrated a positive effect on the periodontal pathogen. MH drug-loaded membranes have no adverse effect on the growth of periodontal ligament fibroblasts in the MTT test. The study suggests that mPEG-PCLA membranes containing MH are a potential antibacterial drug delivery system for local treatment of periodontitis.

scholarly journals SYNTHESIS AND CHARACTERIZATION OF THIOLATED JACKFRUIT SEED STARCH AS A COLONIC DRUG DELIVERY CARRIER

2019 ◽  
pp. 53-62 ◽  
Author(s):  
Sanjoy Das ◽  
Malay K. Das
Keyword(s):  
Drug Delivery ◽  
Release Kinetics ◽  
Drug Loading ◽  
Local Treatment ◽  
Entrapment Efficiency ◽  
Esterification Reaction ◽  
Compatibility Study ◽  
Mice Model ◽  
Drug Delivery Carrier

Objective: Site-specific drug delivery into the colonic region is extremely fascinating for local treatment of various colonic diseases like ulcerative colitis, colon cancer but it should be capable of saving the drug from hydrolysis and degradation. The present study reports the application of jackfruit seed starch and its thiol derivative as a drug delivery carrier for the colon. Methods: The starch was extracted from the jackfruit seeds by water extraction method and modified by the esterification reaction with thioglycolic acid. The thiolated starch was characterized for morphology, functional and flow properties. The safety profile of the thiolated starch was confirmed by acute toxicity study in a mice model as per OECD guidelines 423. The microspheres based on thiolated starch were prepared by ionic gelation method incorporating Ibuprofen as a model drug. The prepared microspheres were characterized for particle size, drug entrapment efficiency, drug loading, compatibility study, surface morphology, in vitro drug release and release kinetics. Results: The result attributed that starch was successfully modified by the thiolation with a degree of substitution of 3.30. The size of prepared microspheres ranges from 825.5±4.58 to 857±6.24 µm, the entrapment efficiencies ranges from 69.23±1.19 to 76.15±0.83 % and the drug loading capacity ranges from 17.75±0.30 to 46.05±0.49 %. The FT-IR, DSC and XRD studies confirmed that there is no interaction within drug and excipients. The thiolated starch microspheres show the maximum release of drug at pH 7.4 in the presence of rat caecal content as compared to pH 1.2 and pH 6.8 for up to 24 h and are following first order release kinetics. Conclusion: These results suggest the application of thiolated jackfruit seed starch could be promising as a long-term drug delivery carrier for the colon.

scholarly journals Fabrication of Chitosan Based Antibacterial Implant for Multibacterial Bone Infection

2021 ◽  
pp. 224-241
Author(s):  
Ashish Y. Pawar ◽  
Sejal R. Jadhav ◽  
Deelip V. Derle
Keyword(s):  
Drug Loading ◽  
Local Treatment ◽  
In Vitro Study ◽  
Bone Infection ◽  
Infection Site ◽  
Ciprofloxacin Hydrochloride ◽  
Surgical Methods ◽  
Evaluation Parameters

Despite advancements in medicines and novel surgical methods, osteomyelitis is still a complex and difficult to treat multi-bacterial bone infection. It generates in tissue necrosis along with rupturing of bone in chronic cases leading towards limited vascularity at infection site, local treatment might not show accountable level of antibiotic at infection site. The present research aims towards development and evaluation of bio-degradable implant of Ciprofloxacin hydrochloride to treat local osteomyelitis. Chitosan is widely investigated biodegradable polymer with hydroxyl moiety which is active and can be altered chemically to develop biomedical and therapeutic dosage forms. Here this active group was modified using epichlorohydrin & crosslinked Chitosan matrices were used as carrier to formulate different Ciprofloxacin implant. In vivo parameters and in vitro study was conducted for optimized batch. The formulation having 40% drug loading (EC4) was found to be optimum when all evaluation parameters were tested. The concentration of Ciprofloxacin Hydrochloride (HCl) in bone and surrounding tissues is much higher than minimum inhibitory concentration (MIC) even after a month. After observing the water uptake and extended release of drug from all formulations the drug loading was found to be higher. The present work concluded that, the highly branched chitosan remarkably reduce the percent (%) drug release up to a month which could be useful in the treatment of osteomyelitis.

ARV-330: Androgen receptor PROTAC degrader for prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 267-267 ◽  
Author(s):  
Taavi K Neklesa ◽  
Meizhong Jin ◽  
Andrew P Crew ◽  
AnnMarie K Rossi ◽  
Ryan R Willard ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Therapeutic Effects ◽  
Preclinical Development ◽  
Protein Levels ◽  
Novel Approach ◽  
Subsequent Degradation ◽  
20 Nm

267 Background: The transition from localized prostate cancer to metastatic disease often involves modulation of the Androgen Receptor (AR). During the disease progression, patients progressing on enzalutamide or abiraterone therapy exhibit amplified AR, increased intra-tumoral androgen production or AR mutations leading to promiscuity to other ligands. Therefore, AR is still the principal driver of the disease. Methods: A novel approach to block AR signaling is to specifically target AR for degradation. To this end, we have developed the PROteolysis TArgeting Chimera (PROTAC) technology that employs hetero-bifunctional small molecules that simultaneously bind VHL E3 ubiquitin ligase and a target of interest (e.g. AR). Due to induced proximity between VHL and AR, an AR PROTAC leads to ubiquitination and subsequent degradation of AR. Results: Our lead AR PROTAC, ARV-330, degrades 92-98% of total AR in all cell lines tested, with 50% degradation concentrations (DC50) < 1nM. AR degradation suppresses the AR-target gene PSA expression, inhibits proliferation, and induces potent apoptosis in VCaP cells with maximal apoptosis observed at 20 nM. While enzalutamide loses its activity in the presence of > 0.5 nM R1881, ARV-330 maintains its activity. In cells containing the ARF876L mutation, enzalutamide is an agonist; however, ARV-330 remains effective. In fact, ARV-330 is able to degrade all clinically relevant AR mutations. ARV-330 exhibits good pharmacokinetic properties, with t1/2 values of several hours and bioavailability of > 80% after sc injection. Treatment of mice with ARV-330, at doses ranging from 0.3 to 10 mg/kg, results in reduction of AR protein levels. The in vitro potency translates into in vivo efficacy, as ARV-330 demonstrates prostate involution in intact mice. In castrated mice implanted with VCaP tumors, ARV-330 shows robust reduction of plasma PSA and blockade of tumor growth. Conclusions: In summary, the AR PROTAC ARV-330 removes AR from prostate cancer cells in a potent manner and produces therapeutic effects as a result. This cellular efficacy has translated into biomarker activity and efficacy in animal models, and ARV-330 is now in preclinical development.

Preparation and Characterization of PEGylated Iron Oxide-Gold Nanoparticles for Delivery of Sulforaphane and Curcumin

Drug Research ◽  
2017 ◽  
Vol 67 (12) ◽  
pp. 698-704 ◽  
Author(s):  
Hossein Danafar ◽  
Ali Sharafi ◽  
Sonia Askarlou ◽  
Hamidreza Manjili
Keyword(s):  
Cell Line ◽  
Water Solubility ◽  
Drug Loading ◽  
In Vitro Study ◽  
Entrapment Efficiency ◽  
Breast Adenocarcinoma ◽  
Therapeutic Effects ◽  
Loading Capacity ◽  
Au Nps

AbstractNatural products have been used for the treatment of various diseases such as cancer. Curcumin (CUR) and sulforaphane (SF) have anti-cancer effects, but their application is restricted because of their low water solubility and poor oral bioavailability. To improve the bioavailability and solubility of SF and CUR, we performed an advanced delivery of SF and CUR with PEGylated gold coated Fe3O4 magnetic nanoparticles (PEGylated Fe3O4@Au NPs) to endorse SF and CUR maintenance as an effective and promising antitumor drugs. The structure of the synthesized nanocarrieris evaluated by, transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR). The results revealed that the size of NPs was 20 nm. They were mono-dispersed in water, with high drug-loading capacity and stability. CUR and SF were encapsulated into NPs with loading capacity of 16.32±0.023% and 15.74±0.015% and entrapment efficiency of 74.57±0.14% and 72.20±0.18% respectively. The in-vitro study of SF and CUR loaded PEGylated Fe3O4@Au NPs on human breast adenocarcinoma cell line (SK-BR-3) confirmed that cytotoxicity of SF and CUR can enhance when they are loaded on PEGylated Fe3O4@Au NPs in comparison to Free SF and void CUR. The results of flow cytometry and real-time PCR shown that nano-carriers can increase therapeutic effects of SF and CUR by apoptosis and necrosis induction as well as inhibiting of migration in SK-BR-3 cell line.

scholarly journals Preparation and Evaluation of Beta sitosterol Nanogel: A Carrier Design for Targeted Drug Delivery system

2018 ◽  
Vol 6 (3) ◽  
pp. 81-87
Author(s):  
Yashashri Mohan Inamdar ◽  
Bhushan Rane ◽  
Ashish Jain
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Transdermal Drug Delivery ◽  
Drug Loading ◽  
Drug Formulation ◽  
Gelling Agent ◽  
Therapeutic Effects ◽  
Transdermal Drug Delivery System

Transdermal drug delivery system is promising but challenging system available for local as well as systemic effect of the drug. The prolonged residence of drug formulation in the skin is important for transdermal drug delivery. Nanogel drug delivery has remained as one of the most challenging task. The objective of the investigation was to develop a nanogel with reduced particle size in order to improve the bioavailability of the hydrophobic drug. The objective of the controlled and sustained delivery is to provide and maintained adequate concentration of drugs at the site of action. Nanogels based materials have high drug loading capacity, biocompatibility and biodegradability which are key points to design the drug delivery system effectively. Drug molecules loaded into the nanogel need to be retained and not to be transported out or leak prematurely while circulating in order to provide maximum therapeutic effects and minimum toxicity or side effects. The present study is to formulate nanosizes dispersion of Beta sitosterol by nanoprecipitation method and incorporating it into the gelling agent to produce nanogel by dispersion method. 1% of carbopol 934 shows better in-vitro drug release than the other concentrations of carbopol 934.

Papain mediated synthesized gold nanoparticles encore the potency of bioconjugated Flutamide

2020 ◽  
Vol 21 ◽  
Author(s):  
Xiao Xu ◽  
Libo Man
Keyword(s):  
Prostate Cancer ◽  
Gold Nanoparticles ◽  
Cancer Cells ◽  
Drug Loading ◽  
Inhibitory Effect ◽  
Therapeutic Drug ◽  
Ros Generation ◽  
High Concentration ◽  
Vis Spectroscopy

Background: Prostate cancer is the second most common cause of male cancer death after lung cancer in the US. Therefore, there is an urgent need for a highly effective therapeutic drug at substantially low doses. Objective: Anti-androgen drug flutamide was delivered to the prostate cancer cells using papain mediated synthesized gold nanoparticles (PGNPs) as the drug delivery system. PGNPs and flutamide worked synergistically against cancer cells. Method: Flutamide was used to bioconjugate with PGNPs to improve its efficacy against prostate cancer. The synthesis and bioconjugation of flutamide with PGNPs (F-PGNPs) were characterized by various characterization techniques such as UV–vis spectroscopy, Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and zeta potential to ensure the synthesis, size, shape, size distribution, and stability. The drug loading efficiency of flutamide in F-PGNPs was confirmed and validated by UV–vis spectroscopy. Eventually, in vitro studies were performed to determine the potency of F-PGNPs, changes in nuclear morphology, and generation of Reactive Oxygen Species (ROS). Results: The efficacy of F-PGNPs (IC50 is 46.54 µg/mL) was found to be improved significantly over pure flutamide (IC50 is 64.63 µg/mL) against human prostate cancer PC–3 cell line whereas F-PGNPs did not show any significant toxicity up to a fairly high concentration toward normal mouse macrophage J774A.1 cells. The apoptotic effects and ROS generation of F-PGNPs were analyzed by increased permeability of the cell membrane and condensed chromatin with deep blue and green fluorescent nucleus, respectively. The results clearly showed that F-PGNPs significantly improved the potency of flutamide by delivering it directly into the nucleus of cancer cells through caveolae-dependent endocytosis. Conclusion: Thus, the greater inhibitory effect of F-PGNPs over the pure drug would be of great advantage during prostate cancer treatment.

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