Delivery Of Antineoplastic Agents Research Articles

Gel Formulations for Topical Treatment of Skin Cancer: A Review.

Skin cancer, with all its variations, is the most common type of cancer worldwide. Chemotherapy by topical application is an attractive strategy because of the ease of application and non-invasiveness. At the same time, the delivery of antineoplastic agents through the skin is difficult because of their challenging physicochemical properties (solubility, ionization, molecular weight, melting point) and the barrier function of the stratum corneum. Various approaches have been applied in order to improve drug penetration, retention, and efficacy. This systematic review aims at identifying the most commonly used techniques for topical drug delivery by means of gel-based topical formulations in skin cancer treatment. The excipients used, the preparation approaches, and the methods characterizing gels are discussed in brief. The safety aspects are also highlighted. The combinatorial formulation of nanocarrier-loaded gels is also reviewed from the perspective of improving drug delivery characteristics. Some limitations and drawbacks in the identified strategies are also outlined and considered within the future scope of topical chemotherapy.

Molecularly imprinted cryogel membranes for mitomycin C delivery

In this study, cryogel-based implantable molecularly imprinted drug delivery systems were designed for the delivery of antineoplastic agent. Mitomycin C imprinted poly(2-hydroxyethyl methacrylate-N-methacryloyl-l-glutamic acid) cryogel membranes were produced by free-radical bulk polymerization under partially frozen conditions. The membranes were characterized by swelling tests, Fourier transform infrared spectroscopy, scanning electron microscopy, surface area measurements and in vitro hemocompatibility tests. In vitro delivery studies were carried out to examine the effects of cross-linker ratio and template content. Mitomycin C imprinted cryogel membranes have megaporous structure (10–100 μm in diameter). The cumulative release of mitomycin C was decreased with increasing cross-linking agent ratio and increased with the amount of template in the cryogel structure. The nature of transport mechanism of the mitomycin C from the membranes was non-Fickian.

Development of Anti-Cancer Stem Cells as Theranostic Agents in the Treatment of Different Cancer Types: An Update

Various unprecedented anti-tumor potential targets that robustly target cancer cells while sparing normal cells have been produced by biomedical research in cancer therapeutic intervention for interrupting disease progression and their cure. Stem cells characterize an accessible cell source for novel cell based clinical therapies by inhibiting tumor progression signalling pathways. They carry distinctive characteristics of isolation and migration to tissue inflammation site, inherited modifiability and protein expression. Stem cells are also used in immune-reconstitution and tissue regeneration. Implication of different types of stem cells as an attractive candidate for targeted delivery of anti-neoplastic agents has emerged as a promising field in anticancer therapy. Mutual interaction between cancer cells and stem cells results in effective and safer clinical therapy for tumors. Keeping in view, this review highlights the potential role of stem cells in the progression of tumor metastasis and also summarizes the role of different signaling pathways in carcinogenesis and their involvement in disease treatment. It also focuses on the current advances in stem cells practice in therapeutics of cancer.

The receptor binding fragment of alpha-fetoprotein is a promising new vector for the selective delivery of antineoplastic agents

The alpha-fetoprotein (AFP) binding protein, a putative AFP receptor, is a tumour marker that is present on the surfaces of malignant cells. AFP enters cells through receptor-mediated endocytosis. The recombinant C-terminal fragment of AFP (AFP-3BC, which consists of amino acid residues 473–596) was obtained by the expression in Escherichia coli. AFP-3BC was shown to be bound specifically to the AFP putative receptor on tumour cells and accumulated by endocytosis in these cells in a similar manner to that of full-length human AFP. In lymphocytes, the binding and endocytosis of AFP-3BC were absent. Thus, the AFP receptor binding site was shown experimentally to be located within the AFP-3BC sequence. A conjugate of synthesised AFP-3BC with the antitumour antibiotic doxorubicin (DOX-AFP-3BC) demonstrated high antitumour activity in vitro. Thus, AFP-3BC can be used successfully as a vector for the targeted selective delivery of drugs into tumour cells.

Effect of X-ray irradiation on expression of organic anion transporting polypeptides

Purpose: Some members of the organic anion transporting polypeptide (OATP) family may play critical roles in determining the concentration of anticancer drugs in targeted organs/cells. The purpose of the present study was to investigate whether radiation can alter the expression of OATP in cancer cells so that OATP can be used as a specific drug target for anti-tumor treatment in combination with radiotherapy.Materials and methods: Two cancer cell lines (HepG2 and MCF7) were irradiated with three doses of X-ray and the expression levels of six OATP were assessed.Results: Expressions of several OATP were altered after irradiation. OATP1A2, an OATP that was found to transport anti-tumor drugs and was undetectable in untreated cells, showed dramatically elevated level of expression after irradiation in MCF7 cells. The combined treatment of X-rays and the OATP1A2 substrate methotrexate exerted a more significant effect on growth rate and cell death compared with radiation or methotrexate treatment alone. At certain time points, X-rays increased OATP1A2 level while suppressing the expression of efflux transporters.Conclusions: Radiation may simultaneously increase the expression of uptake transporters and decrease the level of efflux transporters, suggesting OATP may be considered a novel target for delivery of anti-neoplastic agents in combination with radiotherapy.

On The Biomedical Promise of Cell Penetrating Peptides: Limits Versus Prospects

The cell membrane poses a substantial hurdle to the use of pharmacologically active biomacromolecules that are not per se actively translocated into cells. An appealing approach to deliver such molecules involves tethering or complexing them with so-called cell penetrating peptides (CPPs) that are able to cross the plasma membrane of mammalian cells. The CPP approach is currently a major avenue in engineering delivery systems that are hoped to mediate the non-invasive import of problematic cargos into cells. The large number of different cargo molecules that have been efficiently delivered by CPPs ranges from small molecules to proteins and even liposomes and particles. With respect to the involved mechanism(s) there is increasing evidence for endocytosis as a major route of entry. Moreover, in terms of intracellular trafficking, current data argues for the transport to acidic early endosomal compartments with cytosolic release mediated via retrograde delivery through the Golgi apparatus and the endoplasmic reticulum. The focus of this review is to revisit the performance of cell penetrating peptides for drug delivery. To this aim we cover both accomplishments and failures and report on new prospects of the CPP approach. Besides a selection of successful case histories of CPPs we also review the limitations of CPP mediated translocation. In particular, we comment on the impact of (i) metabolic degradation, (ii) the cell line and cellular differentiation state dependent uptake of CPPs, as well as (iii) the regulation of their endocytic traffic by Rho-family GTPases. Further on, we aim at the identification of promising niches for CPP application in drug delivery. In this context, as inspired by current literature, we focus on three principal areas: (i) the delivery of antineoplastic agents, (ii) the delivery of CPPs as antimicrobials, and (iii) the potential of CPPs to target inflammatory tissues.

Targeted delivery of biologic and other antineoplastic agents.

This review summarizes several strategies under investigation for targeted delivery of antineoplastic agents to tumor cells, which avoids normal tissue damage. Monoclonal antibodies remain the molecules of choice for targeted therapy, and several improvements to immunotargeting are discussed. These improvements include the use of novel radioisotopes, cytokines, new linkers for chemotherapeutic drugs, more potent drugs, and improved immunotoxins. Bifunctional antibodies, in which one antigen-binding site recognizes a tumor-associated antigen and the other an antineoplastic agent, have been investigated for radioimmunotherapy and for the activation of cytotoxic cells for targeted immunotherapy. The activation of relatively nontoxic prodrugs by antibody-enzyme conjugates is increasingly being investigated in an effort to reduce the systemic toxicity associated with conventional chemotherapy. Finally, the use of liposomes as carriers of drugs or as activators of macrophages is described.

Effects of induced hypertension on blood flow and capillary permeability in rats with experimental brain tumors

To study the possibility of enhancing the delivery of antineoplastic agents to tumor tissue, we conducted an experimental study using induced hypertension with angiotensin II in rats with experimental brain tumors. Drug delivery was evaluated by measuring local cerebral blood flow (LCBF) and regional cerebral capillary permeability with quantitative autoradiography. There was no significant difference of LCBF in the central region of tumor tissue between the control group and the induced hypertension group. LCBF in the peripheral region of tumor tissue in the induced hypertension group was significantly higher than that in the control group. On the other hand, despite induced hypertension, no significant changes in the regional cerebral capillary permeability were observed between the groups. These results indicate that delivery of the lipid-soluble antineoplastic agents, which depend upon cerebral blood flow, can be enhanced by induced hypertension.