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1.
Nanomedicine (Lond) ; 18(25): 1855-1873, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37991168

RESUMO

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, typically diagnosed in advanced stages. Chemotherapy is necessary for treating advanced liver cancer; however, several challenges affect its effectiveness. These challenges include low specificity, high dosage requirements, high systemic toxicity and severe side effects, which significantly limit the efficacy of chemotherapy. These limitations can hinder the treatment of HCC. This review focuses on the prevalence of HCC, different types of liver cancer and the staging of the disease, along with available treatment methods. Additionally, explores recent and relevant studies on smart drug- and gene-delivery systems specifically designed for HCC. These systems include targeted endogenous and exogenous stimuli-responsive platforms.


Liver cancer is the third leading cause of cancer deaths in the world that is usually diagnosed in the last stages. Chemotherapy is commonly used to treat advanced liver cancer, but it faces several challenges that reduce its effectiveness. These challenges include low specificity (not targeting cancer cells specifically), high dosage requirements and side effects that can affect anywhere in the body. As a result, the efficacy of chemotherapy is significantly limited, making it difficult to treat liver cancer. This review discusses the prevalence of liver cancer, different types of liver cancer and how the disease is staged. It also explores various treatment methods available for liver cancer. Furthermore, the article explores recent and relevant studies on smart drug- and gene-delivery systems that are specifically designed to target liver cancer. These systems include platforms that respond to targeted and internal or external stimuli. They aim to improve the effectiveness of treatment for liver cancer.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Terapia de Alvo Molecular , Técnicas de Transferência de Genes
2.
Adv Pharm Bull ; 13(3): 532-538, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37646059

RESUMO

Purpose: Poor aqueous solubility hampers the development of several compounds as pharmacological agents. Hence, preparing novel formulations with augmented absorption is a challenge in pharmaceutical industries. In this paper, we have examined the effect of basic amino acids including arginine (ARG), lysine (LYS), and glucosamine (GlucN) on the solubility of ibuprofen (IBU) and piroxicam (PXM) as drugs with limited solubility. We have also studied the effect of the dissolution media with the pH values 1.2 to 7.4. Methods: The saturation shake-flask method was used for solubility studies in the presence of amino acids. Briefly, buffer solutions containing different concentrations of amino acids were prepared. Then, an excess amount of each drug with these buffers was shaken to reach equilibrium. After 48 hours, the upper phase was separated, and solubility was calculated by reading their UV-Vis absorbance. Results: The results illustrated that amino acids increased solubility of both drugs with different ratios, which were pH and concentration-dependent. Solubility improved as the amount of amino acids went up, and this upward pattern was more robust with ARG than LYS. The presence of GlucN in citrate buffer significantly enhanced IBU solubility. The solubility of PXM in accompany of GlucN in water did not change significantly while in citrate buffer solubility enhanced specially at pH 6. Conclusion: Overall, GlucN in citrate buffer and ARG in phosphate buffer could be introduced as the most suitable media for IBU and PXM solubility improvement, respectively.

3.
Int J Mol Sci ; 23(22)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36430951

RESUMO

Aptamers are synthetic single-stranded oligonucleotides (such as RNA and DNA) evolved in vitro using Systematic Evolution of Ligands through Exponential enrichment (SELEX) techniques. Aptamers are evolved to have high affinity and specificity to targets; hence, they have a great potential for use in therapeutics as delivery agents and/or in treatment strategies. Aptamers can be chemically synthesized and modified in a cost-effective manner and are easy to hybridize to a variety of nano-particles and other agents which has paved a way for targeted therapy and diagnostics applications such as in breast tumors. In this review, we systematically explain different aptamer adoption approaches to therapeutic or diagnostic uses when addressing breast tumors. We summarize the current therapeutic techniques to address breast tumors including aptamer-base approaches. We discuss the next aptamer-based therapeutic and diagnostic approaches targeting breast tumors. Finally, we provide a perspective on the future of aptamer-based sensors for breast therapeutics and diagnostics. In this section, the therapeutic applications of aptamers will be discussed for the targeting therapy of breast cancer.


Assuntos
Aptâmeros de Nucleotídeos , Neoplasias da Mama , Humanos , Feminino , Técnica de Seleção de Aptâmeros , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Aptâmeros de Nucleotídeos/uso terapêutico , Sistemas de Liberação de Medicamentos , Ligantes
4.
Int J Pharm ; 625: 122063, 2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-35964827

RESUMO

The development of a therapeutic system for hepatic fibrosis has become a research hotspot to date. Butein, a simple chalcone derivative, displays anti-fibrotic effects through different pathways. However, impurities, low solubility, and low concentration in the target tissue hinder therapy with herbal ingredients. Hepatic stellate cells (HSCs), the vitamin A (VA) storage cells, as the main contributors to liver fibrogenesis, are not readily accessible to drugs owing to their anatomical location. Targeted delivery of therapeutics to the activated HSCs is therefore critical for successful treatment. For these reasons, the current study aimed at increasing butein delivery to the liver. Hence, high purity butein was synthesized in three steps. A novel VA-Myrj52 ester conjugate was also synthesized using all-trans retinoic acid and a hydrophilic emulsifier (Myrj52) as a targeting agent. Next, butein was encapsulated inside the novel VA-modified solid lipid nanoparticles (VA-SLNs) and studied in vitro and in vivo. According to our evaluations, negatively charged SLNs with a mean diameter of 150 nm and entrapment efficacy of 75 % were successful in liver fibrosis amelioration. Intraperitoneal (i.p.) injection of VA-SLNs in fibrotic rats, for four weeks long, reduced serum AST and ALT by 58% (P, 0.001) and 72% (P, 0.05), respectively, concerning the CCl4 group. Additionally, histologic damage score decline and normalization of tissue oxidative stress markers collectively confirmed the efficacy of formulations in hepatic fibrosis and kidney damage amelioration.


Assuntos
Chalconas , Animais , Células Estreladas do Fígado/metabolismo , Lipossomos , Fígado/metabolismo , Cirrose Hepática/metabolismo , Nanopartículas , Ratos , Vitamina A/metabolismo
5.
Expert Opin Drug Deliv ; 19(6): 685-705, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35698794

RESUMO

INTRODUCTION: Compared to normal cells, malignant cancer cells require more iron for their growth and rapid proliferation, which can be supplied by a high expression level of transferrin receptor (TfR). It is well known that the expression of TfR on the tumor cells is considerably higher than that of normal cells, which makes TfR an attractive target in cancer therapy. AREAS COVERED: In this review, the primary focus is on the role of TfR as a valuable tool for cancer-targeted drug delivery, followed by the full coverage of available TfR ligands and their conjugation chemistry to the surface of liposomes. Finally, the most recent studies investigating the potential of TfR-targeted liposomes as promising drug delivery vehicles to different cancer cells are highlighted with emphasis on their improvement possibilities to become a part of future cancer medicines. EXPERT OPINION: Liposomes as a valuable class of nanocarriers have gained much attention toward cancer therapy. From all the studies that have exploited the therapeutic and diagnostic potential of TfR on cancer cells, it can be realized that the systematic assessment of TfR ligands applied for liposomal targeted delivery has yet to be entirely accomplished.


Assuntos
Antineoplásicos , Neoplasias , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Ligantes , Lipossomos/metabolismo , Neoplasias/tratamento farmacológico , Receptores da Transferrina/metabolismo , Transferrina/metabolismo
6.
Acta Pharm Sin B ; 10(7): 1279-1293, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32874828

RESUMO

Liver fibrosis results from chronic damages together with an accumulation of extracellular matrix, and no specific medical therapy is approved for that until now. Due to liver metabolic capacity for drugs, the fragility of drugs, and the presence of insurmountable physiological obstacles in the way of targeting, the development of efficient drug delivery systems for anti-fibrotics seems vital. We have explored articles with a different perspective on liver fibrosis over the two decades, then collected and summarized the information by providing corresponding in vitro and in vivo cases. We have discussed the mechanism of hepatic fibrogenesis with different ways of fibrosis induction in animals. Furthermore, the critical chemical and herbal anti-fibrotics, biological molecules such as micro-RNAs, siRNAs, and growth factors, which can affect cell division and differentiation, are mentioned. Likewise, drug and gene delivery and therapeutic systems on in vitro and in vivo models are summarized in the data tables. This review article enlightens recent advances in emerging drugs and nanocarriers and represents perspectives on targeting strategies employed in liver fibrosis treatment.

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