Pharmaceutical Nanotechnology - Volume 6, Issue 2, 2018

Background: Brain is a delicate organ, separated from general circulation and is characterized by the presence of relatively impermeable Blood Brain Barrier (BBB). The BBB maintains homeostasis in the brain thus restricting the entrance of foreign bodies and several molecules from reaching the brain. As a result several promising molecules do not reach the target site and fail to produce in vivo response. Nevertheless, lipid nanoparticles are taken up readily by the brain because of their lipophilic nature. The bioacceptable and biodegradable nature of lipid nanoparticles makes them less toxic and suited for brain targeting. Objective: In the present review the BBB, mechanism of transport across the BBB, strategies to bypass the blood-brain barrier have been presented. The aptness of lipid nanoparticles for brain targeting has been highlighted. The proposed mechanism of uptake of the lipid nanoparticles, methods of prolonging the plasma retention and various methods of preparation for formulation of effective delivery systems for brain targeting have been included and dealt in this review. Conclusion: Lipid based formulations can be designated as the current and future generation of drug delivery systems as these possess tremendous potential to bypass BBB and reach the target site due to their small size and ability to dodge the reticular endothelial system. However, these nanostructures need to be investigated intensively to successfully reach the clinical trials stage.

Background: Breast cancer is the most widely occurring non-cutaneous cancer in women. Treatment options available for breast cancer are limited and there are a number of toxicity concerns associated with them. Therefore, nanocarrier based approaches have been explored for breast cancer treatment. Nanocarriers implemented for breast cancer treatment are nanoliposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, gold nanoparticles, dendrimers, and protein nanocages. Objective: Objective of this review was to explore the therapeutic efficacy of various nanocarrier systems against breast cancer. Method: Existing literature regarding nanocarrier systems for breast cancer therapy was reviewed using Pubmed and Google Scholar. Results: Nanocarriers may show prolonged circulation time of chemotherapeutic agent with efficient breast tumor targeting. Both active and passive targeting methodologies can be explored to target breast cancer cells using different nanocarriers. Targeted nanocarriers have the capability to reduce side effects caused by various conventional formulations used to treat breast cancer. Conclusion: Various nanocarriers listed above have shown their therapeutic potential in preclinical studies to treat breast cancer. Satisfactory clinical evaluation and scale up techniques can promote their entry into the pharmaceutical market in greater extent.

Background: Radiotherapy is an important protocol in the treatment of cancers, but radioresistance of cancerous cells is a challenge in cancer treatment. Objective: The aim of this study was to evaluate the radiosensitizing effect of Cerium oxide Nanoparticles (CNPs) on human promyelocytic leukemia cells (HL-60). Method: HL-60 cells were treated with CNPs at different concentrations (10-100 μg/ml) and exposed to Ionizing Radiation (IR). The genotoxicity effects of CNPs or/and IR were assessed by micronuclei assay in HL-60 cells. Results: It was found that CNPs increased the frequencies of micronuclei in HL-60 cells. CNPs pretreatment to irradiation significantly increased the IR-induced micronuclei incidences in HL-60 cells. The present study demonstrates CNPs to be an effective sensitizer on DNA damage induced by IR in HL-60 cells. Conclusion: These findings suggest the potential application of CNPs as a highly effective radiosensitizer for the treatment of leukemia.

Background: Patients undergoing chemotherapy can develop resistance not only to the administered drug, but also to many other unrelated types of drugs, a phenomenon known as multidrug resistance. One of the most common mechanisms of multidrug resistance is an elevated expression of drug efflux pumps. Codelivery of an efflux pump inhibitor with a chemotherapeutic can increase the killing of multidrug-resistant cancer cells. Objective: Our hypothesis was that delivering doxorubicin directly to the cytosol of multidrug resistant cancer cells via a folate-targeted liposome loaded with a perfluoropentane emulsion droplet and doxorubicin (folated eLipoDox), along with the delivery of verapamil to block the efflux pumps will prove to be more effective in killing multidrug resistant cancer cells compared to conventional drug delivery. Method: Multidrug-resistant KB-V1 cells and doxorubicin-sensitive KB-3-1 cells were treated with 500 μM verapamil and 6.5 μM doxorubicin for 2 hours. Cell viability was measured 48 hours later via an MTT assay. Results: Doxorubicin-sensitive KB-3-1 cells had a cell viability of 29% when treated with verapamil and folated eLipoDox, whereas multidrug-resistant KB-V1 cells had a cell viability of 25% (p=0.38). The co-delivery of verapamil and folated eLipoDox produced the greatest toxicity to KB-V1 and KB- 3-1 cells. Conclusion: We conclude that the cytosolic delivery of doxorubicin via folated eLipoDox combined with the blocking of export pumps via verapamil can overcome the multidrug resistance of KB-V1 cells and even significantly reduce the viability of doxorubicin-sensitive KB-3-1 cells.

Background: Oral delivery of biopharmaceuticals is limited by the absorption barriers in the Gastrointestinal Tract (GIT) such as low permeability across the biological membranes and the enzymatic degradation by proteases. In this study, lipid-based drug delivery systems were proposed to overcome these obstacles. Objective: The aim of this study was to evaluate the effect of particle preparation methods and excipients on the characteristics of Solid Lipid Microparticles (SLM) and Solid Lipid Nanoparticles (SLN). Method: Different triglycerides (TG) were used as the major excipients for the SLM and SLN. Insulin was used as the model protein; insulin-phospholipid (PL) was prepared to increase drug lipophilicity and compatibility with lipid excipients. Four methods were used for preparing lipid particles, i.e. a Hot Melting Dispersion (HMD) technique, a Solvent Evaporation (SE) method, a modified Solvent Evaporation (mSE) method and a Spray Drying technique. The lipid particles were evaluated in terms of size, size distribution, surface morphology and drug Entrapment Efficiency (EE). Results: The results suggested that SE method was the most suitable method for preparing insulin-PL loaded Solid Lipid Particles (SLP). No differences were observed when the SLP with a Long Chain Triglyceride (LCT) either a Medium Chain Triglyceride (MCT) in term of size. 70-90% of the lipidified insulin was incorporated in the lipid particles. Conclusion: The preparation methods affected the size and morphology of SLP significantly, and the selection of lipid excipient should be done based on specific application requirements. Furthermore, the use of the lipidified protein was an efficient way to encapsulate protein in lipid carriers.

Objective: The aim of the present study was to develop and evaluate nanostructured lipid carrier based topical hydrogel of mometasone furoate for the treatment of psoriasis. Method: Drug loaded NLCs were successfully developed by microemulsion technique. Pseudo ternary phase diagrams were constructed using different combinations of surfactant and co-surfactants to study the microemulsion existence range. Different compositions were selected from the phase diagram showing maximum microemulsion region and were converted into NLCs by dilution in water (1:20). The optimized formulation was characterised for droplet size, zeta potential, entrapment efficiency and morphology was studied using Transmission Electron Microscopy. Ex vivo permeation studies were carried out using Wistar rat skin. The potential of this formulation in treating psoriatic inflammation was studied using imiquimod induced skin inflammation animal model. Results: The optimized formulation (F4) has droplet size of 163.2±0.522 nm, zeta potential - 0.086±0.099 mV and entrapment efficiency of 60.0±0.187%. Transmission electron microscopy confirmed spherical shape of nanostructured lipid carrier. Carbopol 940 was used to convert NLC dispersion into NLC based hydrogel to improve its viscosity for topical administration. Drug permeation studies showed prolonged drug release from the NLC based gel as compared to marketed formulation following Higuchi release kinetics. The skin deposition of MF loaded NLC based hydrogel was found to 2.5 fold higher than marketed formulation with primary skin irritation index of 0.20. In vivo studies showed complete clearance of parakeratosis by treatment with the prepared NLC formulation. Accelerated stability studies signify high robustness scale of optimized formulation under one month storage period. Conclusion: The prepared NLC based formulation has proved to be a promising carrier system for the treatment of psoriasis.