Pharmaceutical Nanotechnology - Volume 6, Issue 4, 2018

Hepatocellular carcinoma (HCC) causes significant morbidity and high fatal outcome globally. Conventional therapeutic strategies for HCC have achieved significant improvements, but they have limitations and are far from ideal. Novel nanoparticulate drug delivery systems have recently presented great therapeutic potential for cancer therapeutics. Appropriate and accurate animal models (main mice) are the basis of preclinical and translational research of nanoparticulate drug formulations in HCC. This review will provide an overview of different animal models of HCC, with a particular emphasis on those applied to assess the clinical potential for drug nanopharmaceutics.

Cancer cells are able to avoid immune surveillance and exploit the immune system to grow and metastasize. With the development of nano- and micro-particles, there has been a growing number of immunotherapy delivery systems developed to elicit innate and adaptive immune responses to eradicate cancer cells. This can be accomplished by training resident immune cells to recognize and eliminate cells with tumor-associated antigens or by providing external stimuli to enhance tumor cell apoptosis in the immunosuppressive tumor microenvironment (TME). In this review we will focus on nano- and micro-particle (NP and MP) based immunotherapies and vaccines used to elicit a potent and sustained antitumor immune response.

Background: Mesoporous silica nanoparticles (MSNs) are emerging as one of the new and promising nanomaterials for biomedical applications, but enough investigation has not been done in the field of the biocompatibility of MSNs in vitro condition. Objective: The present study aims to investigate the toxicity of mesoporous silica nanoparticles in BM-MNCs and SHSY5Y Cell. Method: The synthesis of MSN was performed and it was characterized for its size by SEM and XRD. The cellular toxicity of MSN was investigated by MTT assay as well as LDH assay in BMMNCs and SHSY5Y Cell. Results: In this article, cellular toxicity of mesoporous silica has been targeted keeping in view the size, toxicity, dose administered and in vitro toxicity. In the present study, mesoporous silica was synthesized and characterized for its size via SEM and XRD as 123.05 nM. The antibacterial test via disc diffusion assay was performed and no significant antimicrobial effect was found at low dose i. e less than 150 uM. The in vitro toxicity of MSN in bone marrow mononuclear cells and SHSY5Y cell was investigated in a time and dose-dependent manner. These results also confirmed no significant toxic effect at a low dose while at the higher doses, toxicity was observed. Conclusion: Altogether, this article illuminates mesoporous silica as safe nanoparticle at low doses for drug delivery. The present finding will help researchers to develop and target MSN nanoparticlebased therapeutics for several applications in biological science.

Aim: The present investigation was aimed to formulate and evaluate Metformin loaded pectin (PCM) nanoparticles (NPs) for sustained action for management of Type 2 Diabetes Mellitus (T2DM). Method: The nanoparticles were formulated by ionic gelation technique. The nano-formulations were subjected for the analyses of entrapment efficiency and drug release stud for 12h. The optimized formulation examined various in vitro characterizations such as particle size, zeta potential, surface morphology and FTIR studies. The in vitro heamocomptability, protein binding stability and glucose uptake studies were performed with nanoparticles. Results: The PCMNP-4 showed drug entrapment efficiency, 68 ± 4.2 % and demonstrated favourable in vitro prolonged release characteristics. The mean particles diameter of optimized formulation was 482.7 nm and 0.270 poly dispersity index (PI), had spherical shape and zeta potential of (+38.85 mV). In addition, the nanoparticles were reasonably stable in the presence of excess bovine serum albumin, which suggested that the nanoparticles may also be stable in the blood stream. The percentage of haemolysis induced by Metformin and placebo PCNPs were less than 5%. The results indicated that the PCMNPs are hemocompatible and therefore, safe for oral administration. The glucose uptake was increased 1.5 fold in RBCs and L6 skeleton muscle cell line compared with Metformin. Conclusion: Hence, the designed nanoparticle system could possibly be advantageous in terms of prolonged release, to achieve reduced dose frequency and improve patient compliance.

Objective: The present research work was designed to formulate and evaluate solid lipid nanoparticles (SLN) loaded gel of Dapsone (DS). An attempt was made to develop topical gel with better skin permeation rate. Method: The SLN formulations of DS were prepared by microemulsion technique and evaluated for its in vitro characteristics. The effect of DS concentration in lipid phase (X1), Gelucire:Precirol ratio (X2) and lipid:Smix ratio (X3) on entrapment efficiency (Y1) and drug release (Y2) from SLN was studied using Box-Behnken design. The result of dependent variables was used to generate polynomial equations and the surface response and counterplots. The optimized SLN formulation was incorporated into the gel using 1% carbopol-934 as a gelling agent. The SLN loaded gel was characterized for pH, viscosity, percent drug content, in vitro drug release and ex vivo permeation through rat skin. Results: The optimized DS SLN formulation, with 20% drug loading, 0.5:1 as Gelucire : Precirol ratio in lipid phase and 1:3 as Lipid : Smix ratio, showed 95.64±0.2% drug entrapment, 61.1±0.6% of drug release after 8 h, particle size of 168.5 nm with polydispersity index of 0.335 and zeta potential of -16.8±6.1 mV. DS SLN gel demonstrated biphasic release pattern with greater drug permeation through rat skin (Jss, 39.27±2.1 μg/cm2/hr) as compared to plain DS gel (Jss, 22.64±1.8 μg/cm2/hr). Conclusion: The present study demonstrated DS SLN gel as a possible alternative to a conventional topical formulation for the treatment of acne.

Background and Objectives: The combination of nano-metals and antibacterial agents could improve the efficacy of antibiotics against pathogens. This study suggested a combination method for increasing the antibacterial and anti-biofilm activity of ampicillin and gentamicin using iron oxide nanoparticles. Method: The synthesis of lipoamino acid-coated IONs (LION14) was done by co-precipitation method. The LION14s were characterized by several techniques. The antimicrobial and biofilm inhibitory activities of nanoparticles at three-time intervals were investigated alone and in combination with ampicillin and gentamicin against Staphylococcus aureus and Escherichia coli. In-vitro cytotoxicity assay was performed to assess potential toxic effects of LION14 on mammalian cell line. Results: Detailed characterization of the LION14 confirmed the presence of about 7 nm sized magnetic nanoparticles coated with lipo-amino acid. The antimicrobial and biofilm inhibitory effects of ampicillin and gentamicin were increased in the presence of the appropriate concentration of LION14s against tested microorganisms. The highest synergistic effect was observed for ampicillin against Escherichia coli. Also in the presence of antibiotics, the antibacterial and biofilm inhibitory effect of LION14 was significantly increased. The cytotoxicity results of LION14 showed the minimum cytotoxicity on the L929 cell line. Conclusion: The result showed that the combination of antibiotics with LION14 provides enhanced antimicrobial and anti-biofilm results for antibiotics along with acceptable biocompatibility. This synergistic effect could be used against biofilm forming bacteria and resistant microorganisms in the future.