Envisioning Clinical Management of Breast Cancer: a Comprehensive Review.

Coming to the edge of disease manufacturing in the twenty-first-century, breast cancer occupies a terrifying scenario in the globe, especially in adult women. Its curiosity endeavours remarkable advances made during the past decennaries for cancer treatment and diagnosis.

Lomustine Incorporated Lipid Nanostructures Demonstrated Preferential Anticancer Properties in C6 Glioma Cell Lines with Enhanced Pharmacokinetic Profile in Mice.

Effective treatment of glioma still stands as a challenge in medical science. The work aims for the fabrication and evaluation of lipid based nanostructures for improved delivery of lomustine to brain tumor cells. Experimental formulations (LNLs) were developed by modified lipid layer hydration technique and evaluated for different in vitro characteristics like particle size analysis, surface charge, surface morphology, internal structure, in vitro drug loading, drug release profile etc. Anticancer potential of selected LNLs was tested in vitro on C6 glioma cell line. Electron microscopic study depicted a size of less than 50 nm for the selected LNLs along 8.8% drug loading with a sustained drug release tendency over 48 h study period. Confocal microscopy revealed extensive internalization of the selected LNL in C6 cells. LNLs were found more cytotoxic than free drug and blank nanocarriers as depicted from MTT assay. The selected LNL showed improved pharmacokinetic profile both in blood and brain in the experimental mice models along with negligible hemolysis in mice blood cells. Further studies are warranted for the future translation of LNLs at clinics.

Targeting to Brain Tumor: Nanocarrier-Based Drug Delivery Platforms, Opportunities, and Challenges.

Cancer is a class of disorder characterized by anomalous growth of cells escalating in an uncontrolled way. Among all the cancers, treatment of cancerous brain tumors has been a tough challenge for the research scientists. Moreover, the absence of early-stage symptoms delays its diagnosis, consequently worsening its severity. Conventional treatments such as surgery, radiation, and chemotherapy are still linked with several limitations. The therapeutic effect of most of the anticancer drugs is highly restricted by their inability to pass the blood-brain barrier, low solubility, limited therapeutic window, and so on. Alarming incidences of brain cases associated with low survival rate across the globe coupled with the inefficiency of current treatment strategies have forced the formulation scientists to investigate nanotechnology-based advanced therapeutic approaches to tackle the disease. Various nanoplatforms such as polymeric nanoparticles (NPs), nanoliposomes, dendrimers, carbon nanotubes, and magnetic NPs have been reported in the past years to improve the drug administration into brain tumor cells and to minimize their off-target distribution for lesser side effects and better treatment outcomes. The review presents updated information on the nanocarrier-based drug delivery systems reported in the past few years for the treatment of brain tumor along with new advancements in this field. It also throws some light on the recent challenges faced in the practical field for the successful clinical translation of such nanodrug carriers along with a discussion on the future prospects.

AQbD Driven Development of an RP-HPLC Method for the Quantitation of Abiraterone Acetate for its Pharmaceutical Formulations in the Presence of Degradants.

OBJECTIVES: Abiraterone acetate is a well-known anticancer drug and a steroidal derivative of progesterone for treatment of patients with hormone-refractory prostate cancer. Chemometrics-assisted reverse phase high performance liquid chromatography (RP-HPLC) development of the drug abiraterone acetate has been employed in this study using an analytical quality by design (AQbD) approach. MATERIALS AND METHODS: Drug separation was performed using a Princeton Merck-Hibar Purospher STAR (C18, 250 mm × 4.6 mm) i.d., 5 µm particle size) with ultraviolet detection at 235 nm. A Box-Behnken statistical experimental design with response surface methodology was executed for method optimization and desired chromatographic separation from its formulation with a few numbers of experimental trials. The impact of three independent variables, namely, composition of the mobile phase, pH, and flow rate, on response retention time and peak area was studied by constructing an arithmetic model from these variables. RESULTS: Optimized experimental conditions for the proposed work include the mobile phase acetonitrile and phosphate buffer (10 mM KH2PO4) (20:80 %v/v). At the concentration range of 2-100 µg/mL, a linear calibration curve was found. Recovery was performed at three concentrations and was foun to be between 98% and 102%. The 3D response surface curves revealed that mobile phase composition and flow rate were the most substantial critical factors affecting desired responses. CONCLUSION: An attempt has been made to develop and validate an economical, precise, robust, stability-indicating AQbD-based RP-HPLC method that can be employed successfully for the routine analysis of abiraterone acetate in quality control labs.

Nanobiotechnology-based drug delivery in brain targeting.

Blood brain barrier (BBB) found to act as rate limiting factor in drug delivery to brain in combating the central nervous system (CNS) disorders. Such limiting physiological factors include the reticuloendothelial system and protein opsonization, which present across BBB, play major role in reducing the passage of drug. Several approaches employed to improve the drug delivery across the BBB. Nanoparticles (NP) are the solid colloidal particle ranges from 1 to 1000 nm in size utilized as career for drug delivery. At present NPs are found to play a significant advantage over the other methods of available drug delivery systems to deliver the drug across the BBB. Nanoparticles may be because of its size and functionalization characteristics able to penetrate and facilitate the drug delivery through the barrier. There are number of mechanisms and strategies found to be involved in this process, which are based on the type of nanomaterials used and its combination with therapeutic agents, such materials include liposomes, polymeric nanoparticles and non-viral vectors of nano-sizes for CNS gene therapy, etc. Nanotechnology is expected to reduce the need for invasive procedures for delivery of therapeutics to the CNS. Some devices such as implanted catheters and reservoirs however will still be needed to overcome the problems in effective drug delivery to the CNS. Nanomaterials are found to improve the safety and efficacy level of drug delivery devices in brain targeting. Nanoegineered devices are found to be delivering the drugs at cellular levels through nono-fluidic channels. Different drug delivery systems such as liposomes, microspheres, nanoparticles, nonogels and nonobiocapsules have been used to improve the bioavailability of the drug in the brain, but microchips and biodegradable polymeric nanoparticulate careers are found to be more effective therapeutically in treating brain tumor. The physiological approaches also utilized to improve the transcytosis capacity of specific receptors expressed across the BBB. It is found that the low density lipoproteins related protein (LPR) with engineered peptide compound (EpiC) formed the platform incorporating the Angiopep peptide as a new effective therapeutics. The current challenges are to design and develop the drug delivery careers, which must be able to deliver the drug across the BBB at a safe and effective manner. Nanoparticles are found to be effective careers in delivery of conventional drugs, recombinant proteins, vaccines as well as nucleotides. Nanoparticlulate drug delivery systems are found to be improving in the pharmacokinetic strategies of the drug molecules such as biodistribution, bioavailability and drug release characteristics in a controlled and effective manner with site specific drug delivery targeting to tissue or cell with reduction in toxic manifestation. Therefore, the use of nanotechnology in the field of pharmaceutical biotechnology helps in improving the drug delivery strategy including the kinetics and therapeutic index to solve the delivery problems of some biotech drugs including the recombinant proteins and oligonucleotides. This review is made to provide an insight to the role of nanobiotechnology in drug delivery and drug targeting to brain and its recent advances in the field of drug delivery systems.

Submicron-size biodegradable polymer-based didanosine particles for treating HIV at early stage: an in vitro study.

Human immunodeficiency viruses (HIV) hide themselves in macrophages at the early stage of infection. Delivering drug in a sustained manner from polymeric nanoparticles in those cells could control the disease effectively. The study was intended to develop poly(d,l-lactic-co-glycolic acid)-based nanoparticles containing didanosine and to observe their uptake by macrophages in vitro. Various physicochemical evaluations related to nanoparticles, such as drug-excipient interaction, surface morphology, particle size, zeta potential, polydispersity index, drug loading, in vitro drug release and nanoparticle-uptake by macrophages in vitro were determined. Homogenising speeds and drug-polymer ratio varied drug loading and polydispersity index of nanoparticles, providing sustained drug release. Dimethyl sulphoxide/polyethylene glycol improved drug loading predominantly. Nanoparticle-uptake by macrophages was concentration dependent. Experimental nanoparticles successfully transported didanosine to macrophages in vitro, suggesting reduction of dose, thus minimising toxicity and side effects. Developed nanoparticle may control HIV infection effectively at an early stage.