1- Introduction

2- Experimental section

3- Results and discussion

4- Conclusions

References

Abstract

In this paper, a targeting hyaluronic acid (HA)/mesoporous silica nanoparticle (MSN) based drug delivery system (DDS) with dual-responsiveness was prepared for cancer therapy. To avoid the side reaction between the anti-cancer drug doxorubicin hydrochloride (DOX) and HA, host-guest interaction was applied to fabricate the DDS named DOX@MSN-SS-N=C-HA. The “nanocontainer” MSN was modified with benzene ring via both pH-sensitive benzoic imine bond and redox-sensitive disulfide linkage. When DOX was loaded in the pores of MSN, the channels were then capped by the “gatekeeper” β-CD grafted HA (HA-g-CD) through host-guest interaction between β-CD and benzene. HA endowed the drug carriers with the targeting capability in CD44 over-expressed cancer cells. After cellular uptake, the carriers could rapidly release DOX for cell apoptosis due to both the hydrolysis of benzoic imine bond at low pH and the cleavage of disulfide bond at a high concentration of glutathione (GSH) intracellular. In vitro drug release studies and in vitro cytotoxicity studies were taken to investigate the dual-responsiveness of the carriers. And the CD44-receptor mediated cancer cell targeting capability was investigated as well. In conclusion, the targeted dual-responsive complex DDS fabricated through host-guest interaction has promising potential in cancer therapy.

Introduction

Chemotherapy remains one of the major therapeutic approaches applied to treat cancer in clinic. However, the disadvantages of traditional chemotherapeutic drugs such as unfavorable pharmacokinetics, poor biodistribution and lack of selectivity for target tissues reduce the utilization of the drugs and cause serious side effects [1]. To tackle these problems, anti-cancer drug delivery systems (DDSs) based on nanotechnology have been introduced and developed rapidly in recent decades [1–4]. DDSs such as liposomal daunorubicin (DaunoXome), pegylated liposomal doxorubicin (Doxil), albumin nanoparticle based Nan-paclitaxel (Abraxane) and polymeric micelle paclitaxel (GenexolPM) have already been approved for clinical treatment of cancer [3,4]. These nanosized DDSs can be accumulated in tumor tissues more easily via enhanced permeability and retention (EPR) effect to improve the pharmacokinetics and biodistribution of the drugs, as well as to reduce their side effects [5]. Though the commercial DDSs represented by the liposomal doxorubicin can overcome part of the shortcomings of traditional anticancer drugs, they cannot or only modestly improve patients’ overall survival [3,6–9]. Therefore, more efforts are needed to develop novel advanced DDSs. The properties including controlled drug release based on stimuli- sensitivity [10,11] and ligand-mediated active cancer targeting [12–15] introduced make the newly reported DDSs with better therapeutic effects [1–4]. During the past decade, mesoporous silica nanoparticle (MSN) based DDSs have attracted considerable attention from scientists worldwide [16,17]. MSNs can be simply synthesized with tunable size, shape, pore size and volume [17,18], and are easy surface functionalization [16]. These advantages, as well as the high drug loading capacity and good biocompatibility, ensure that MSNs are excellent choices for designing safe and efficient drug carriers [16–18].

1- Introduction

2- DDS for targeted BC treatment

3- Conclusion and outlook

References

Abstract

Bladder cancer is a severe disease that threatens human health. The high recurrence rate and severe side-effects of traditional bladder cancer therapy require more efficient and higher targeting treatment. Drug delivery systems especially being endowed with the targeting property may provide a feasible means to solve such problems. Herein, we have reviewed the recent progress of the drug delivery systems aiming at bladder cancer therapy especially focusing on their targeting strategies. Additionally, we give some outlook of the design on targeting strategy for more effective anti-cancer applications.

Introduction

Cancer is a category of disease originating from unregulated cell growth and such abnormal cells are able to spread or invade other parts of our body. It is a major public health problem and becomes the second leading cause of death worldwide. Among them, bladder cancer (BC) tops the list of the estimated new cases and deaths [1]. In Europe, BC is the 5th most common cancer type for both sexes affecting rather men than women [2]. In US, BC ranks the 4th most common caner and the 8th in mortality in men [1]. In principle, BC is a rather heterogeneous disease, resulting in a challenge in classification, staging and grading. Generally, 70% of bladder urothelial cell carcinomas represent a superficial disease called nonmuscle-invasive BC, while the other 30% develop a muscle-invasive disease bearing the risk of metastatic spread of the tumor [3]. The standard scheme for superficial BC treatment is surgical transurethal resection with an 80% early success rate. Unfortunately, among them, 70% of those patients develop tumor recurrence within 5 years after surgical transurethal resection [4]. Therefore, chemotherapy still plays an important role in the prevention of tumor recurrence and progression. Although systemic or intravesical chemotherapy using the first-line chemotherapeutic agents (cisplatin, taxanes, gemcitabine, etc.) enables long-term survival in some patients, the high recurrence rate and severe side-effects still hinder BC therapy. Thus, more efficient and higher targeting treatment is in urgent need to improve the quality of the BC patients’ lives.

1- Introduction

2- Material and methods

3- Results and discussion

4- Conclusions

References

Abstract

Mesoporous silica nanoparticles with folic acid (MSN−COOH-Tet-HBP-FA) are able to mediate targeting and have a pH stimulation response character, and therefore have been successfully synthesized as vectors for antitumor drug delivery. The model drug is tetrandrine (Tet). The chemical structure and properties of these NPs were characterized through systematic characterization analyses. Their drug loading capacity was significantly improved through carboxy modification (26.86 % in max), and they exhibited pH-dependent drug release profiles(“zero pre-release” within 20 h in a normal physiological environment). In vitro cytotoxicity and cell uptake of the as-synthesized NPs in Hela and A549 cells were also evaluated, and exhibited high cytotoxicity and cell-targeted uptake capacity. It was concluded that MSN−COOH-Tet-HBP-FA could be used as a promising drug delivery system for cancer therapy.

Introduction

Cancer is currently considered to be a leading factor that threatens human lives, and chemotherapy remains one of the most common methods used for cancer treatment. However, traditional drugs are nonspecific and cannot discriminate cancer cells and normal cells, which not only limits the accumulation of drugs in tumor cells, but also leads to systemic toxicity and adverse side effects. In order to improve the efficacy of chemotherapy, many studies have been devoted to the development of tumor-targeted nanocarriers, which can be used to control the delivery of antitumor drugs. Using the enhanced permeation and retention (EPR) effects, researchers have developed multiple nanocarrier platforms, including liposomes, polymer nanoparticles, nano-micelles, and dendrimers, which are used to delivery anticancer drugs into tumor tissues. However, the EPR effect is not efficient enough to eradicate the side effects of cytotoxic drugs and to exert the anticancer therapy selectively in cancer cells. In order to enhance the targeting and tumoral uptake ability, the external surface of nanocarrier is often modified with various ligands, which can significantly enhance the interaction between the cancer cells and the nanocarriers[. Targeted agents typically include antibodies (such as monoclonal antibodies), peptides (such as Arg-Gly-Asp (RGD)), and small molecule compounds (such as folic acid).

1- Introduction

2- Materials and methods

3- Results and discussion

4- Conclusions

References

Abstract

Nowadays, a combinatorial drug delivery system that simultaneously transports two or more drugs to the targeted site in a human body, also recognized as a dual-drugs delivery system, represents a promising strategy to overcome drug resistance. Solid lipid nanoparticles loaded with clotrimazole (CLZ) and alphalipolic acid (ALA), considered as an effective agent in the reduction of reactive oxygen species, can enhance anti-infective immunity being proposed as a non-toxic and mainly non-allergic dual-drugs delivery system. In this study, uncoated and cationic CLZ-ALA-loaded SLN were prepared and compared. Suspensions with a narrow size distribution of particles of mean size below 150 nm were obtained, having slight negative or highly positive zeta potential values, due to the presence of the cationic lipid, which also increased nanoparticles stability, as confirmed by Turbiscan® results. Calorimetric studies confirmed the rationale of separately delivering the two drugs in a dual-delivery system. Furthermore, they confirmed the formation of SLN, without significant variation in presence of the cationic lipid. In vitro release studies showed a prolonged drug release without the occurrence of any burst effect. In vitro studies performed on 25 strains of Candida albicans showed the antimicrobial drug activity was not altered when it was loaded into lipid nanoparticles. The study has proved the successfully encapsulation of CLZ and ALA in solid lipid nanoparticles that may represent a promising strategy to combine ALA protective effect in the treatment with CLZ.

Introduction

Fungal infections, most of all candidiasis, represent an increasing challenge affecting global health, that in many cases produces morbidity and mortality in immunocompromised and intensive care unit patients [1,2]. Among different types of fungi, Candida albicans represents the main cause of fungal diseases, responsible of both orally and vaginally yeast infections, overall when a decrease in Lactobacillus concentration appears [3]. Usually, polyenes, echinocandins and azoles are the most used drugs for the treatment of fungal infections [4], even if the requirement of early treatment and the occurrence of side effects still limit the efficiency of the therapy. Among azoles, Clotrimazole (CLZ) is one of the most broad-spectrum antimycotic drug used for the treatment of vulvovaginal and oropharyngeal candidiasis [5]. Moreover, CLZ has been claimed to show a selective antibacterial activity [6,7] and ability to inhibit in vitro Streptococcus mutans biofilm and virulence [8]. CLZ antifungal activity is related to its capability to interfere with the biosynthesis of ergosterol, the major component of the fungal cytoplasmic membrane, with the consequent depletion of ergosterol and its replacement with the aberrant sterol species, 14-amethylsterol, thus disturbing the membrane permeability and fluidity [9]. However, the increasing antifungal resistance to azoles, mainly among immunocompromised patients, strongly limits the effective treatment of mycoses [10]. Combinatorial drug delivery is a promising strategy to prevent potential drug resistance [11]. We have recently demonstrated the possibility to improve CLZ effectiveness exploiting its nanoencapsulation in lipid nanoparticles prepared by additionally using of essential oils from Mediterranean area, highlighting their synergistic effect [12].