Pharmaceutical Nanotechnology - Volume 5, Issue 2, 2017

Background: Targeting drug delivery is an attractive research area, as it enables localized treatment, improves the efficacy of therapeutics and reduces systemic toxicity. Colon targeting delivery is particularly beneficial to the treatment of colon diseases, such as inflammatory bowel disease and colon cancer, due to the improved local drug concentrations. The traditional strategies for colon targeting delivery include time-dependent and pH-dependent technologies, etc. In recent years, nanotechnology has emerged as a novel and efficient tool for targeting drug delivery. After oral administration, nano-based formulations are able to protect drug from the harsh gastrointestinal environment and selectively increase the drug concentration at the disease site. Various orally administered drug-loaded nano-systems for colon targeting delivery have been well documented and shown great potentials in colon disease therapy. Objective: In this work, we aim to provide a comprehensive understanding of the recent progress in the area of colon targeting delivery in combination with introduction of the pathophysiological changes of diseased colon sites and the obstacles for drug delivery.

Background: Skin cancer is depicted to be the most common malignant disease across the globe that is frequently diagnosed in people bearing light skin. Three common forms of skin cancers are squamous cell carcinoma, basal cell carcinoma, and malignant melanoma. Treatment of skin cancers comprises of various forms of management strategies that can help in curing the disease including the use of several therapeutic agents. Though numerous therapies have been explored till date to deliver the active therapeutics, nanoparticulate based targeted therapy has garnered considerable interest and is a promising approach in treating skin cancers. Objective: The present review aims to explore a novel nano-sized carrier, carbon nanotubes for the delivery of various actives researched for skin cancer treatment. The write up traces the pre-clinical and clinical reports on carbon nanotubes. The feasibility of the nanoparticulate system has been elaborated inclusive of the safety and toxicological aspects of the carrier system. Conclusion: From the reviewed literature it can be concluded that carbon nanotubes are the emerging treatment modality in skin cancers as they offer targeted delivery to the cancerous cells, act selectively and provide better penetration in the neoplastic cells due to improved permeability and retention effect.

Background: Breast cancer, apart from skin cancer, is the most common cancer among women accounting for nearly 1 in 3 cancers and the second leading cause of cancer-related death among women after lung cancer. Finding new approaches to treat such cancers is critically important. Objective: This work investigated the ability of a simple system based on paclitaxel conjugated gold nanoparticles (AuNP) to induce efficient cytotoxicity against T47D breast cancerous cells at different pH values. Methods: The synthesis and characterization of nanoparticles using two approaches are presented. In one case, the AuNP capping agent is exchanged for a long chained thiol with a terminal carboxylic acid which can then be connected to paclitaxel (termed the Chemical Modification approach) while in the other case, the thiol capping agent is chemically modified with the paclitaxel first and then exchanged onto the AuNP (termed the Ligand Exchange approach). Cytotoxicity of conjugates based on gold nanoparticles at pH 7.4 (normal physiological pH) and 6.5 (more acidic pH found near tumors) against the T47D breast cancer cell line was assessed using the 3-(4, 5 dimethylthiazol-2-yl)-2, 5- diphenyltetrazolium (MTT) viability assay. Results: T47D viability decreased significantly after treatment with the chemical modification conjugate at pH 6.5 compared to that at pH 7.4. The ligand exchange conjugate also decreased cell viability with a gap of 10 % between the two pHs. Conclusion: These nanoparticles are promising conjugates for the treatment of breast cancer using small amounts of the active chemotherapy agents which will lead to fewer side effects.

Background: Chemoprevention is a strategy which uses drugs which are traditionally not used as anti-cancer drugs; however, they prevent the carcinogenesis. Meloxicam (MLX) is traditionally used as a non-steroidal anti-inflammatory drug (NSAID), but it has been proven to have activity against colorectal cancer. Subsequently MLX seems to be a likely candidate to be utilized in the chemopreventive therapy of colorectal cancer. However, MLX poses shortcomings with respect to its dose required to elicit cytotoxicity. To improve the formulation, we used Quality by design (QbD) for optimization. QbD is a method that employs quality-improving scientific methods that build quality into the formulation by isolating the factors which affect the critical quality attributes of the formulation. The aim of the present study was to utilize the principles of QbD to formulate MLX into a formulation so as to exploit its potential to the fullest. Methods: Conventional (CLM) and PEGylated liposomes (MPL) of MLX was prepared using hydrogenated soya phosphatidylcholine (HSPC), distearyl phosphatidyl glycerol (DSPG), cholesterol and 1, 2-distearoyl- phosphatidylethanolamine-methyl-polyethyleneglycol conjugate-2000 sodium salt (MPEG 2000 DSPE). The liposomes were prepared using thin film hydration method. The optimization of the formulation was done by employing the QbD approach. The formulation was optimized on the basis of the factors which were affecting the critical quality attributes (CQAs) such as particle size and entrapment efficiency. The final optimized formulation was characterized by assessing the particle size, percent entrapment efficiency, zeta potential, long-term stability, morphology, in vitro release and in vitro cytotoxic activity. Result: PEGylated liposomes having high percent entrapment efficiency (87.25 %±0.72%) could be obtained. The entrapment of drug in the liposomes was confirmed using Differential Scanning Calorimetry (DSC), Fourier Transform Infrared spectroscopy (FT-IR) and Powder X-Ray diffraction (PXRD) studies. The mean particle size of the liposomes was 113 nm±67nm and they were found to exhibit sustained release profile (56.59 %±0. 43% drug in 24h). The Small Angle Neutron Scattering (SANS) analysis revealed that the liposomes were uniform sized LUVs (nm) and were spherical in shape. The shape of the liposomes was further confirmed by transmission electron microscopy (TEM). Long term stability study indicated that the formulation was stable for three months. Sulphorhodamine B (SRB) cytotoxicity assay was carried out in HT-29 cell to prove that the PEGylated liposomal formulations had higher cytotoxicity than the conventional liposomes after 48 hours of incubation. Conclusion: The study affirmed that MLX loaded PEGylated liposomes had superior in vitro cytotoxicity as compared to the free drug as well as conventional liposomes. QbD resulted in the fabrication of a stable liposomal formulation with all the desirable characteristics. Hence, MLX loaded PEGylated liposomes can be considered to be a promising system for the delivery of MLX.

Background: Multiple applications of antipsychotic agents are the main obstacle in the treatment of schizophrenia. Due to behavioral abnormalities, low compliance is observed in most of the psychotic patients. Designing of new drug delivery systems to overcome compliance problem seems to be necessary. In situ forming implants are a suitable choice for the delivery of antipsychotic agents due to their easy administration process and sustained release kinetics. Objective: In this study, a novel poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) based nanoporous in situ implant system is developed for delivery of aripiprazole. Methods: Entrapment efficiency, drug loading, rheological features, morphological characteristics and release profile of nano-porous in situ implant system are analyzed in this study. Results: Entrapment efficiency and drug loading coefficient were modeled and impact of different experimental parameters was analyzed using D-optimal study. Entrapment efficiency and drug loading were optimized at 99.32% and 75.23%, respectively. Rheological analyses demonstrated that the developed formulation is a highly cross-linked gel with possible capability for controlled delivery of aripiprazole. According to the FTIR studies, aripiprazole was intact within polymer networks. SEM and light microscopic analyses proved the acceptable morphological characteristics of in situ gels. Release studies demonstrated a biphasic pattern of release. After initial burst release, a sustained pattern was observed for 18 days. The release data was fitted to Korsmeyer-Peppas model and release pattern was found out to be Fickian. In addition, the release profile was compared with novel pluroniccarrageenan based hydrogel system. Conclusion: PHBV based in situ forming implant seems to be a novel formulation for delivery of Aripiprazole.

Background: The emergence of drug resistant pathogens is a major concern to the scientific community. Novel approaches such as the use of functionalized nanomaterials with antimicrobial activity is required to treat infectious diseases. Objective: In the present study, the metallic nanoparticles (iron, gold, zinc oxide and copper oxide) were evaluated for the antimicrobial, biofilm inhibitory and anti-infective activity against human pathogens methicillin resistant Staphylococcus aureus and Pseudomonas aeruginosa PA01. Methods: The efficacy of nanoparticles on the planktonic growth of clinically relevant pathogens was determined by MIC. Further, the effect of nanoparticles was studied on their biofilms using crystal violet microtiter plate assay and fluorescent microscopy. The cytotoxicity of nanoparticles was studied in HT29 cell line. Results: The nanoparticles of copper and zinc oxide (size < 50 nm) were more effective against Grampositive and Gram-negative pathogens in comparison to gold and iron nanoparticles. The ZnO nanoparticles had an MIC in the range of 3.125 μg/ ml and 6.25 μg/ ml against the tested pathogens. The nanoparticles at the tested concentration reduced biofilm burden by > 75% in the pathogens. The nanoparticles showed cytotoxicity in HT 29 at 20 μg/ ml. Conclusion: The results of the study showed that of all the tested nanoparticles, ZnO nanoparticles had significant antimicrobial activity against the drug resistant pathogens and could be used at concentrations less toxic to mammalian cells. Hence, ZnO nanoparticles have the potential for the design of novel antibacterial agents and therapeutics.

Background: Dissipative particle dynamics (DPD) is a simulation method that has one of its applications in the field of pharmaceutical science and drug delivery. Objective: DPD is employed to study morphology and some other characteristics of polymeric nanomicelles. Two systems were considered in this study: system A which includes curcumin, Polycaprolactone (PCL), Polyethylene glycol (PEG) and water beads and system B which includes paclitaxel, Polylactic acid (PLA), PEG and water beads. Method: In this study we focused on the simulation of drug entrapment in polymeric micelles using DPD method. Results: Results indicated that the qualitative comparison of polymeric-micelles with different compositions, after carefully tuning input parameters and simulation conditions, can be successfully performed using DPD. Conclusion: Considering real state of a system for DPD simulation will have a great impact on the reliability of the simulation results.