Antibody-mediated drug delivery.

Passive and active targeted nanoparticulate delivery systems show promise to compensate for lacking properties of conventional therapy such as side effects, insufficient efficiency and accumulation of the drug at target site, poor pharmacokinetic properties etc. For active targeting, physically or covalently conjugated ligands, including monoclonal antibodies and their fragments, are consistently used and researched for targeting delivery systems or drugs to their target site. Currently, there are several FDA approved actively targeted antibody-drug conjugates, whereas no active targeted delivery system is in clinical use at present. However, efforts to successfully formulate actively targeted delivery systems continue. The scope of this review will be the use of monoclonal antibodies and their fragments as targeting ligands. General information about targeted delivery and antibodies will be given at the first half of the review. As for the second half, fragmentation of antibodies and conjugation approaches will be explained. Monoclonal antibodies and their fragments as targeting ligands and approaches for conjugating these ligands to nanoparticulate delivery systems and drugs will be the main focus of this review, polyclonal antibodies will not be included.

Development and evaluation of polymeric micelle containing tablet formulation for poorly water-soluble drug: tamoxifen citrate.

Poor aqueous solubility is one of the key reasons for slow dissolution rate and poor intestinal absorption and finally that causes low therapeutic efficacy of many existing drugs. Tamoxifen citrate (TMX) (BCS Class II drug) with low water solubility has poor oral bioavailability in the range of 20%-30%, therefore, high doses are required for treatment with TMX. Self-assemblage of amphiphilic polymers leads to the formation of polymeric micelles which makes them unique nano-carriers with excellent biocompatibility, low toxicity, enhanced blood circulation time, and solubilization of poorly water-soluble drugs. In this study poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) triblock copolymer, which has been approved by FDA for oral application was used to benefit its micellar solubilization effect. Self-assembled micelles were prepared for the delivery of TMX and this way TMX solubility was increased approximately 60 times. TMX-treated cells showed 38.06 ± 1.5% viability at 50 µM concentration for 24 h; 66.71 ± 11.6% viability at 25 µM concentration for 48 h, at the same conditions TMX-loaded micelles exhibited 24.994 ± 0.25% and 43.36 ± 4.37% cell viability, respectively (p < 0.05). These results showed that the encapsulation of TMX into PEG-PPG-PEG micelles facilitated the cellular uptake, which led to an increased cytotoxicity in MCF-7 cancer cells. Tablet formulation containing lyophilized TMX-loaded micelles was showed an improved dissolution than commercial TMX tablet (Tamoxifen® TEVA). It can be reasonably expected that the obtained drug dissolution rate and increased cytotoxicity to tumor cells will result in an increase of TMX bioavailability and tolerability associated with an important dose reduction and decreased side effects.

Current Advances in Nanopharmaceuticals.

Nanotechnology is one of the hot topics not only in pharmaceutical industry, but also in many others that are currently existing in our daily lives. Since the last two decades, many nanotechnology based drugs have been introduced in the market providing new and optimized treatment perspectives. In addition to that, local regulatory authorities also meet new challenging issues regarding the development process of the nanopharmaceuticals. It is a clear fact that the novelty of nanopharmaceuticals also include a more precise clarification process on the efficacy and safety of the formulations for the benefit of public health. Therefore, current scientific improvements as well as current regulatory perspectives are reflected in this review.

Novel advances in targeted drug delivery.

Developing a new drug molecule is not only time-consuming and expensive, but also mostly a failing process. However, improving bioavailability, targetability, efficacy or safety of old drugs could be more effective way to use them in clinic. For these purposes, so many strategies including individualising drug therapy, nanoparticle-based drug delivery systems, drug conjugates, therapeutic drug monitoring, stimuli-sensitive targeted therapy are investigated intensely. Depending on the desired application or targeted site, nanoparticles can be administrated as orally, locally, topically and systemically. Currently, the Food and Drug Administration and the European Medicines Agency approved nanoparticles are mostly aimed to treat cancer. Although some of these formulations were approved by Food and Drug Administration and/or European Medicines Agency to use in clinic, most of them have fell down to pass either pre-clinical or clinical trials. To have high approval rate, failure reasons need to be better understand.