Recent Advances in Lipid-Based Nanovesicular Delivery Systems for Melanoma Therapy
01 Jan 2021-Critical Reviews in Therapeutic Drug Carrier Systems (Begel House Inc.)-Vol. 38, Iss: 4, pp 1-38
TL;DR: Various lipid-based nano-formulations used in the diagnosis, treatment, or both for melanoma are discussed and a state-of-the-art overview of alternative therapeutic approaches for the treatment of melanoma, such as photodynamic, immune, and gene therapies are presented.
Abstract: Melanoma is one of the most aggressive forms of cancer with limited treatment options available. Successful treatment involves a combination of surgical resection of the tumor; chemotherapy and immunotherapy. Given their complex nature, the rapid development of drug resistance and metastatic spread, nanotechnology-based therapeutics are an attractive option for effective melanoma treatment. Nano-vesicular-based delivery systems hold the promise of aiding in the diagnosis and treatment of melanoma. These formulations can improve targeted delivery, deliver insoluble drugs belonging to class II, biopharmaceutical classification system, and alter drug pharmacokinetics and exposure profiles. These nanometer-sized carriers predominantly bypass the reticuloendothelial system and, thereby, improve blood circulation time and enhance tumor cell uptake with reduced toxicity. In this review, various lipid-based nano-formulations used in the diagnosis, treatment, or both for melanoma are discussed. Utilization of these na-no-formulations with a single drug or a combination of drugs, nucleic acid-based compounds (small interfering RNA, DNA) and targeting antibodies as other possibilities for melanoma are reviewed. We also present a state-of-the-art overview of alternative therapeutic approaches for the treatment of melanoma, such as photodynamic, immune, and gene therapies.
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TL;DR: In this paper, the authors discuss the advantages of transdermal route over oral and parenteral routes for popular chemotherapeutic drugs and also discuss a possible in silico approach, Formulating for Efficacy™, to design trans-dermal formulations that would probably be economical, robust, and more efficacious.
Abstract: Chemotherapeutic drugs are primarily administered to cancer patients via oral or parenteral routes. The use of transdermal drug delivery could potentially be a better alternative to decrease the dose frequency and severity of adverse or toxic effects associated with oral or parenteral administration of chemotherapeutic drugs. The transdermal delivery of drugs has shown to be advantageous for the treatment of highly localized tumors in certain types of breast and skin cancers. In addition, the transdermal route can be used to deliver low-dose chemotherapeutics in a sustained manner. The transdermal route can also be utilized for vaccine design in cancer management, for example, vaccines against cervical cancer. However, the design of transdermal formulations may be challenging in terms of the conjugation chemistry of the molecules and the sustained and reproducible delivery of therapeutically efficacious doses. In this review, we discuss the nano-carrier systems, such as nanoparticles, liposomes, etc., used in recent literature to deliver chemotherapeutic agents. The advantages of transdermal route over oral and parenteral routes for popular chemotherapeutic drugs are summarized. Furthermore, we also discuss a possible in silico approach, Formulating for Efficacy™, to design transdermal formulations that would probably be economical, robust, and more efficacious.
16 citations
TL;DR: Current nanosystems used in the diagnosis and treatment of melanoma are discussed, including lipid systems, inorganic nanoparticles, polymeric systems, and natural nanosSystems.
Abstract: Melanoma is a malignant tumor arising in melanocytes from the basal layer of the epidermis and is the fifth most commonly diagnosed cancer in the United States. Melanoma is aggressive and easily metastasizes, and the survival rate is low. Nanotechnology-based diagnosis and treatment of melanoma have attracted increasing attention. Importantly, nano drug delivery systems have the advantages of increasing drug solubility, enhancing drug stability, prolonging half-life, optimizing bioavailability, targeting tumors, and minimizing side effects; thus, these systems can facilitate tumor cytotoxicity to achieve effective treatment of melanoma. In this review, we discuss current nanosystems used in the diagnosis and treatment of melanoma, including lipid systems, inorganic nanoparticles, polymeric systems, and natural nanosystems. The excellent characteristics of novel and effective drug delivery systems provide a basis for the broad applications of these systems in the diagnosis and treatment of melanoma, particularly metastatic melanoma.
10 citations
TL;DR: A review of different types of dermal/transdermal DDSs, along with a critical discussion of the advantages and disadvantages of these systems can be found in this article .
TL;DR: In this article , a review highlights recent advances in targeted nanoparticle drug delivery systems for melanoma therapy, which encourage drug accumulation at the tumor site, enhance antitumor efficacy, and reduce systemic toxicity.
TL;DR: In this paper , a novel approach was developed for CDDP encasement within liposome based on the formation of a coordination bond between the platinum (II) atom and a carboxylic group in aspartic acid (AA) and glutamic acid (GA).
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TL;DR: This review of the recent research on the endocytosis and exocyTosis of functionalized nanoparticles based on various sizes, shapes, and surface chemistries contributes to the design of safe nanoparticles that can efficiently enter and leave human cells and tissues.
Abstract: Engineered nanoparticles that can be injected into the human body hold tremendous potential to detect and treat complex diseases. Understanding of the endocytosis and exocytosis mechanisms of nanoparticles is essential for safe and efficient therapeutic application. In particular, exocytosis is of significance in the removal of nanoparticles with drugs and contrast agents from the body, while endocytosis is of great importance for the targeting of nanoparticles in disease sites. Here, we review the recent research on the endocytosis and exocytosis of functionalized nanoparticles based on various sizes, shapes, and surface chemistries. We believe that this review contributes to the design of safe nanoparticles that can efficiently enter and leave human cells and tissues.
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TL;DR: The aim of this review is to describe the "perfect vector" for systemic gene therapy against cancer based on the advantages and disadvantages of existing vectors and on the hurdles encountered with these carriers.
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TL;DR: Although non-viral vectors are less efficient than viral ones, they have the advantages of safety, simplicity of preparation and high gene encapsulation capability.
668 citations
TL;DR: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.
Abstract: Purpose To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). Patients and methods Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. Results Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. Conclusion Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.
612 citations
TL;DR: In vitro toxicities demonstrated superiority of the targeted dual-drug combination NPs over NPs with single drug or nontargeted NPs, revealing the potential of a single, programmable nanoparticle to blend and deliver a combination of drugs for cancer treatment.
Abstract: The genomic revolution has identified therapeutic targets for a plethora of diseases, creating a need to develop robust technologies for combination drug therapy. In the present work, we describe a self-assembled polymeric nanoparticle (NP) platform to target and control precisely the codelivery of drugs with varying physicochemical properties to cancer cells. As proof of concept, we codelivered cisplatin and docetaxel (Dtxl) to prostate cancer cells with synergistic cytotoxicity. A polylactide (PLA) derivative with pendant hydroxyl groups was prepared and conjugated to a platinum(IV) [Pt(IV)] prodrug, c,t,c-[Pt(NH3)2(O2CCH2CH2COOH)(OH)Cl2] [PLA-Pt(IV)]. A blend of PLA-Pt(IV) functionalized polymer and carboxyl-terminated poly(d,l-lactic-co-glycolic acid)-block-poly(ethylene glycol) copolymer in the presence or absence of Dtxl, was converted, in microfluidic channels, to NPs with a diameter of ∼100 nm. This process resulted in excellent encapsulation efficiency (EE) and high loading of both hydrophilic platinum prodrug and hydrophobic Dtxl with reproducible EEs and loadings. The surface of the NPs was derivatized with the A10 aptamer, which binds to the prostate-specific membrane antigen (PSMA) on prostate cancer cells. These NPs undergo controlled release of both drugs over a period of 48–72 h. Targeted NPs were internalized by the PSMA-expressing LNCaP cells via endocytosis, and formation of cisplatin 1,2-d(GpG) intrastrand cross-links on nuclear DNA was verified. In vitro toxicities demonstrated superiority of the targeted dual-drug combination NPs over NPs with single drug or nontargeted NPs. This work reveals the potential of a single, programmable nanoparticle to blend and deliver a combination of drugs for cancer treatment.
562 citations