Targeting luteinizing hormone-releasing hormone: A potential therapeutics to treat gynecological and other cancers.

Cancer is a prime healthcare problem that is significantly responsible for universal mortality. Despite distinguished advancements in medical field, chemotherapy is still the mainstay for the treatment of cancers. During chemotherapy, approximately 90% of the administered dose goes to normal tissues, with mere 2-5% precisely reaching the cancerous tissues. Subsequently, the resultant side effects and associated complications lead to dose reduction or even discontinuance of the therapy. Tumor directed therapy therefore, represents a fascinating approach to augment the therapeutic potential of anticancer bioactives as well as overcomes its side effects. The selective overexpression of LHRH receptors on human tumors compared to normal tissues makes them a suitable marker for diagnostics, molecular probes and targeted therapeutics. These understanding enabled the rational to conjugate LHRH with various cytotoxic drugs (doxorubicin, DOX; camptothecin etc.), cytotoxic genes [small interfering RNA (siRNA), micro RNA (miRNA)], as well as therapeutic nanocarriers (nanoparticles, liposomes or dendrimers) to facilitate their tumor specific delivery. LHRH conjugation enhances their delivery via LHRH receptor mediated endocytosis. Numerous cytotoxic analogs of LHRH were developed over the past two decades to target various types of cancers. The potency of LHRH compound were reported to be as high as 5,00-10,00 folds compared to parent molecules. The objective of this review article is to discuss reports on various LHRH analogs with special emphasis on their prospective application in the medical field. The article also focuses on the attributes that must be taken into account while designing a LHRH therapeutics with special account to the biochemistry and applications of these conjugates. The record on various cytotoxic analogs of LHRH are also discussed. It is anticipated that the knowledge of therapeutic and toxicological aspects of LHRH compounds will facilitate the development of a more systematic approach to the targeted delivery of cytotoxic agents using peptides.

Experimental Models for Evaluation of Nanoparticles in Cancer Therapy.

Nanoparticles (NPs), the submicron-sized colloidal particles, have recently generated enormous interest among biomedical scientists, particularly in cancer therapy. A number of models are being used for exploring NPs safety and efficacy. Recently, cancer cell lines have explored as prominent experimental models for evaluating pharmacokinetic parameters, cell viability, cytotoxicity and drug efficacy in tumor cells. This review aims at thorough compilation of various cancer cell lines and in vivo models for evaluation of efficacy of NPs on one platform. This will provide a basis to explore and improvise pre-clinical models as a prelude to successful cancer research.

Significance of Various Experimental Models and Assay Techniques in Cancer Diagnosis.

The experimental models are of vital significance to provide information regarding biological as well as genetic factors that control the phenotypic characteristics of the disease and serve as the foundation for the development of rational intervention stratagem. This review highlights the importance of experimental models in the field of cancer management. The process of pathogenesis in cancer progression, invasion and metastasis can be successfully explained by employing clinically relevant laboratory models of the disease. Cancer cell lines have been used extensively to monitor the process of cancer pathogenesis process by controlling growth regulation and chemo-sensitivity for the evaluation of novel therapeutics in both in vitro and xenograft models. The experimental models have been used for the elaboration of diagnostic or therapeutic protocols, and thus employed in preclinical studies of bioactive agents relevant for cancer prevention. The outcome of this review should provide useful information in understanding and selection of various models in accordance with the stage of cancer.

Luteinizing hormone-releasing hormone peptide tethered nanoparticulate system for enhanced antitumoral efficacy of paclitaxel.

AIM: Paclitaxel (PTX) is an effective anticancer agent used in the therapy of a wide variety of cancers. However, the drug is difficult to formulate due to its low solubility, and therefore, it is administered under slow infusion with castor oil/ethanol solution as surfactant that causes serious side effects. This investigation investigates leutinizing hormone releasing hormone (LHRH)-tethered nanparticulate system as modality for cancer-specific delivery of PTX and therefore minimizing the adverse effects. MATERIALS & METHODS: LHRH-tethered poly(lactic-co-glycolic acid) copolymer with poly ethylene glycol side chain was synthesized, characterized and employed to formulate PTX-loaded nanoparticulate system. RESULTS & CONCLUSION: The developed nanoparticulate appears to be proficient in carrying as well as targeted delivery of PTX with improved therapeutic efficacy and better safety.

Galactose engineered solid lipid nanoparticles for targeted delivery of doxorubicin.

The present investigation reports the preparation, optimization, and characterization of surface engineered solid lipid nanoparticles (SLNs) encapsulated with doxorubicin (DOX). Salient features such as biocompatibility, controlled release, target competency, potential of penetration, improved physical stability, low cost and ease of scaling-up make SLNs viable alternative to liposomes for effective drug delivery. Galactosylation of SLNs instructs some gratifying characteristic, which leads to the evolution of promising delivery vehicles. The impendence of lectin receptors on different cell surfaces makes the galactosylated carriers admirable for targeted delivery of drugs to ameliorate their therapeutic index. Active participation of some lectin receptors in immune responses to antigen overlaid the application of galactosylated carriers in delivery of antigen and immunotherapy for treatment of maladies like cancer. These advantages revealed the promising potential of galactosylated carriers in each perspective of drug delivery. The developed DOX loaded galactosylated SLNs formulation was found to have particle size 239 ± 2.40 nm, PDI 0.307 ± 0.004, entrapment efficiency 72.3 ± 0.9%. Higher cellular uptake, cytotoxicity, and nuclear localization of galactosylated SLNs against A549 cells revealed higher efficiency of the formulation. In a nutshell, the galactosylation strategy with SLNs could be a promising approach in improving the delivery of DOX for cancer therapy.

Transdermal delivery of cyclodextrin-solubilized curcumin.

The purpose of the present investigation was to explore the effect of cyclodextrin (CD) as permeation enhancer through rat skin in the form of a valuable and stable transdermal drug delivery system by exploiting its favorable properties. Phase-solubility studies demonstrated that the CD:drug ratio 1:2 was employed in complexation. Solid-state characterizations of complexes was performed by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared, nuclear magnetic resonance spectrophotometry analysis, and scanning electron micrograph. The HP-ß-CD by virtue of its greater stability than the pure curcumin (CMN), allowed greater transdermal flux of CMN indicative of enhanced permeation via CMN-2-hydroxy propyl ß cyclodextrins (HP-ß-CD). Permeability studies of drug, complex, and with various penetration enhancers (PEs), were performed through rat skin, highlighted a favorable effect of CDs on drug permeation rate, due to its solubilizing action; in contrast with unpredictably poor skin permeation of pure drug. The complexes were found to cause relatively less irritation as compared to the pure drug and drug with PEs in skin irritation studies. The anti-inflammatory activity using paw odema model showed that the formulations of CMNCur-HP-ß-CD complex exhibited significant (p < 0.001) decrease in paw edema volume than its pure CMN gel demonstrating enhanced biological activity.

Carbon nanotube exploration in cancer cell lines.

Complete with extraordinary structures and properties, carbon nanotubes (CNTs) have recently emerged as a potential new option for use in cancer treatment. During recent years, cancer cell lines have also been explored as prominent experimental models for evaluating pharmacokinetic parameters, cell viability, cytotoxicity and drug efficacy in tumor cells. Thus, cell lines have emerged as the best-fit model that has been thoroughly investigated and explored. This review focuses on potential applications and a compilation of various cancer cell lines used to evaluate CNT efficacy on one platform. This is likely to aid the researchers in exploring another dimension of CNTs in cancer treatment.