Current Drug Delivery - Volume 17, Issue 10, 2020

The prevalence of liver cancer is increasing over the years and it is the fifth leading cause of mortality worldwide. The intrusive features and burden of low survival rate make it a global health issue in both developing and developed countries. The recommended chemotherapy drugs for patients in the intermediate and advanced stages of various liver cancers yield a low response rate due to the nonspecific nature of drug delivery, thus warranting the search for new therapeutic strategies and potential drug delivery carriers. There are several new drug delivery methods available to ferry the targeted molecules to the specific biological environment. In recent years, the nano assembly of lipoprotein moieties (lipidic nanoparticles) has emerged as a promising and efficiently tailored drug delivery system in liver cancer treatment. This increased precision of nano lipoproteins conjugates in chemotherapeutic targeting offers new avenues for the treatment of liver cancer with high specificity and efficiency. This present review is focused on concisely outlining the knowledge of liver cancer diagnosis, existing treatment strategies, lipoproteins, their preparation, mechanism and their potential application in the treatment of liver cancer.

Quercetin (QT, 3,3′,4′,5,7-pentahydroxyflavone), is a natural flavonoid with nutritional value and acts as a potential free-radical scavenger (antioxidant). QT has also been explored for its anti-cancer as well as anti-proliferative activities against numerous cancerous cells. Moreover, QT exhibits significant pro-apoptotic activity against tumor cells and is well established to control the growth of different carcinoma cells at various phases of the cell cycle. Hence, it can reduce the burden of human solid cancer and metastasis. Both these activities have been established in a diverse class of human cell lines in-vitro as well as in animal models (in-vivo). Apart from the promising therapeutic activities of QT molecule, their applications have been limited due to some major concerns, including low oral bioavailability and poor aqueous solubility. Also, rapid gastrointestinal digestion of QT seems to be a key barrier for its clinical translations for oral drug delivery in conventional dosage form. Henceforth, to overcome these drawbacks, QT is loaded with liposomal systems, which exhibit promising outcomes in the upregulation of QT by the epithelial system and also improved its targeting at the site of action. Furthermore, Liposomes based Drug Delivery Systems (LDDS) have showed significant therapeutic activity with conjugated drug moiety and exhibit safety, biocompatibility, biodegradability, and mitigated toxicity despite having certain limitations associated with physiological and biological barriers. Herein, in this review, we have focused on the mechanism related with the chemotherapeutic activity of QT and also discussed the promising activity of QT-loaded LDDS as a potent chemotherapeutic agent for cancer therapy.

Cancers are life threatening diseases and their traditional treatment strategies have numerous limitations which include poor pharmacokinetic profiles, non-specific drug distribution in the body tissues and organs and deprived tumor cells penetration. This attracted the attention of researchers to tailor efficient drug delivery system for anticancer agents to overcome these limitations. Liposomes are one of the newly developed delivery systems for anticancer agents. They are vesicular structures, which were fabricated to enhance drug targeting to tumor tissues either via active or passive targeting. They can be tailored to penetrate tumor cells membrane which is considered the main rate limiting step in antineoplastic therapy. This resulted in enhancing drug cellular uptake and internalization and increasing drug cytotoxic effect. These modifications were achieved via various approaches which included the use of cell-penetrating peptides, the use of lipid substances that can increase liposome fusogenic properties or increase the cell membrane permeability toward amphiphilic drugs, surface modification or ligand targeted liposomes and immuno-liposomes. The modified liposomes were able to enhance anticancer agent’s cellular uptake and this was reflected in their ability to destroy tumor tissues. This review outlines different approaches employed for liposomes modification for enhancing anticancer agent’s cellular uptake.

Since the discovery of liposomes, these vesicular carriers have attracted the researchers from all the vistas of the biomedical domain to explore and harness the potential benefits. Many novel drug delivery-based products have been approved by the United States Food and Drug Administration (USFDA) and other federal agencies of the globe, out of which the major share is of the liposomes and related carriers. Taking cognizance of it, the US-FDA has recently come up with ‘Guidance for Industry on Liposome Drug Products’. In cancer management, chemotherapy is the most frequently employed approach which is still not devoid of untoward challenges and side effects. In chemotherapy, the taxanes, esp. Docetaxel shares a huge percentage in the prescription pattern. Also, the first marketed liposomal product was encasing one drug of this category. Henceforth, the present review will highlight the advances in the delivery of taxanes, in particular docetaxel, with an emphasis on the need, success and pharmacoeconomic aspects of such vesicular-carrier mediated docetaxel delivery.

Background: The present work aimed to develop an ethosomal gel of naproxen sodium for the amelioration of rheumatoid arthritis. Objective: In the present work, we have explored the potential of ethosomes to deliver naproxen into deeper skin strata. Further, the anti-inflammatory efficacy of naproxen ethosomal formulation was assessed using the carrageenan-induced rat paw edema model. Methods: Naproxen sodium nanoethosomes were prepared using different proportions of lipoid S100 (50mg-200mg), ethanol (20-50%) and water, and were further characterized on the basis of vesicle morphology, entrapment efficiency, zeta potential, in-vitro drug release and ex-vivo permeation studies. Results: The optimized ethosomal formulation was found to have 129 ± 0.01 nm particle size, 0.295 Polydispersity Index (PDI), -3.29 mV zeta potential, 88% entrapment efficiency and 96.573% drug release in 24 hours. TEM and SEM analysis of the optimized formulation showed slightly smooth spherical structures. The Confocal laser scanning microscopy showed that ethosomes could easily infiltrate into deeper dermal layers (upto 104.9μm) whereas the hydroalcoholic solution of the drug could penetrate up to 74.9μm. Further, the optimized ethosomal formulation was incorporated into 1% carbopol 934 gel base and optimized wherein the transdermal flux was found to be approximately 10 times more than the hydroethanolic solution. Also, the in-vivo pharmacodynamic study of the optimized ethosomal gel exhibited a higher percentage inhibition of swelling paw edema than marketed diclofenac gel. Conclusion: The ethosomal gel was successfully developed and has shown the potential to be a good option for the replacement of conventional therapies of rheumatoid arthritis.

Purpose: Hepatocellular carcinoma (HCC) is a common liver malignancy, which has a low survival rate of all cancers. 5-fluorouracil (5-FU) is clinically recognized to treat HCC. However, the success of this therapy is highly limited due to rapid clearance and non- selective distribution. Cholesterol- conjugate (5-FUC) loaded liposomes proposed to facilitate the transport of 5-FUC into tumor cells via Low-Density Lipoprotein receptor (LDL receptor) that overexpressed in HCC. Thus, the aim of this study was to use 5-FUC loaded liposome as a promising strategy to combat HCC and improve the response of HCC to chemotherapy. Methods: 5-FUC and 5-FU loaded liposomes were optimized based on Cholesterol (CHO) ratio and type of phospholipid to achieve a potential effect on HCC. Liposomes were prepared by the thin-film hydration method, and evaluated in terms of particle size, polydispersity, zeta potential, Entrapment Efficiency (EE), morphology, drug release and cytotoxicity. Results: The obtained liposomes had a suitable nano-range particle size with negative zeta potential, and acceptable EE%. In vitro drug release of 5-FUC loaded liposomes showed a lower cumulative release over 24 h as compared to 5-FU loaded liposomes. 5-FUC loaded liposomes exhibited a higher in vitro cytotoxic effect as compared to the free drug and 5-FU loaded liposomes against HepG2 cell lines after 48 h via MTT assay. Conclusion: These results concluded that 5-FUC loaded liposomes could be used as an alternative tactic to increase the therapeutic index of 5-FU and pave the way for potential clinical applications.

Colon cancer is one of the most prevalent diseases, and traditional chemotherapy has not been proven beneficial in its treatment. It ranks second in terms of mortality due to all cancers for all ages. Lack of selectivity and poor biodistribution are the biggest challenges in developing potential therapeutic agents for the treatment of colon cancer. Nanoparticles hold enormous prospects as an effective drug delivery system. The delivery systems employing the use of polymers, such as chitosan and pectin as carrier molecules, ensure the maximum absorption of the drug, reduce unwanted side effects and also offer protection to the therapeutic agent from quick clearance or degradation, thus allowing an increased amount of the drug to reach the target tissue or cells. In this systematic review of published literature, the author aimed to assess the role of chitosan and pectin as polymer-carriers in colon targeted delivery of drugs in colon cancer therapy. This review summarizes the various studies employing the use of chitosan and pectin in colon targeted drug delivery systems.