Current Drug Therapy - Volume 9, Issue 3, 2014

Recent advances in cancer immunotherapy have significantly improved patient life expectancy, either prophylactically or by active treatment of existing malignancies. Effective immune response by host innate and adaptive immune systems can be generated by targeting critical elements of these immune systems which include antigenpresenting cells (APC), toll-like receptors (TLR), and natural killer (NK) cells, as well as specific tumor sites which display tumor specific tumor-associated antigens. One of the major hurdles in the development of therapeutic cancer vaccines arises from the various immunosuppressive mechanisms powered by tumor cells including down-regulation of immunoresponsive antigens and cytokines. Significant strides have been made in the last decade in the identification of specific tumor receptors and tumor-specific tissue-associated antigens. Gaining a deeper level of understanding of the mechanisms by which various effectors meditate immune response and the interplay between various components of innate and adaptive immune systems has spurred research in this field. This review will discuss the innovative approaches for design and active targeted delivery of vaccines to cancers and solid tumors. Delivery systems investigated for this purpose predominantly fall into two main categories; namely biological and physical systems. Biological vaccine delivery systems include bacterial ghosts, plasmid DNA, modified dendritic cells (DCs), whole cells and tumor cell lysates, and modified viral vectors etc. Physical delivery systems include nanoparticulate and nanocolloidal systems as liposomes, polymerosomes, dendrimers, etc. The efficiency of targeting by both types of systems can be further improved by surface modification by antibodies and ligands to effectively target the appropriate tumor target.

Vaccines are primarily employed for triggering the acquired immune response of the body to combat against diverse pathogenic organisms. Conventional approaches for vaccine delivery possess multiple challenges for effective delivery owing to lack of potential for targeting ability to a particular antigen and protection of antigens from physiological environments of body. In the past a few decades, nanocolloidal carriers have gained higher attention in vaccine delivery due to advantages of targeting ability, reduced immunogenicity and significant augmentation in immune response. Instances of colloidal carriers employed for vaccine delivery include liposomes, niosomes, microspheres, proteosomes, virosomes and virus like particles, reconstituted influenza viruses, immunostimulating complexes, antigen cochleates, etc. Further, surface engineering of these carriers with ligands, functional moieties and monoclonal antibodies has yielded enhanced immune recognition potential to the vaccine antigens for eliciting immune response by promoting differentiation of the antigen specific memory T-cells. In a nutshell, the present review provides an updated and exhaustive account on the recent advancements in various colloidal delivery systems employed for vaccine delivery outlining their potential applications, mechanism of augmenting the immune response and instances of the products existing in market in an explicit manner.

Pulmonary vaccine delivery has gained increasing attention during the last decade. This vaccination method has advantages other than parenteral vaccination such as it omits the application of needle. The appropriate formulation of antigens can result improved stability complications associated with conventional vaccines. Antigens formulated as nano carriers reach the respiratory airways of the lungs providing greater chance of uptake by relevant immune cells. These advances promise to accelerate the development and testing of new pulmonary vaccines against many human diseases.

Oral delivery of vaccines is able to induce systemic as well as mucosal immune responses but is largely inefficient due to intestinal degradation and impermeable barrier property of GIT of administered antigen. Efforts are being made to develop a safe and effective oral vaccination by offering resistant against acidic and enzymatic degradation before reaching to the target site. Several strategies are developed to target antigen to the gut associated lymphoid tissue (GALT) present in the intestine where antigen-specific immune responses are initiated. This review discusses various technologies and targets for antigen delivery to induce protective immunization by oral vaccine.

Finding specific inhibitors for the immunodeficiency syndrome caused by virus, HIV-1 or HIV-2 is still a difficult task. HIV most commonly uses CCR5 and CXCR4 as a co-receptor along with CD4 to enter the target cells. CCR5 plays a main role in the integration of the virus inside the host cells by the interaction of CCR5 with the gp120 of the virus. Hence, CCR5 has been considered as a potential drug target in the field of HIV, and researchers are trying to find inhibitors or antagonists that can be targeted against CCR5 which can act as an entry inhibitor. In our current study, ligand-based pharmacopore modeling was done for 41 analogs of maraviroc which are substituents of 1- Amido-1-phenyl- 3-piperidynylbutanes. It results in the formulation of a five-point hypotheses pharmacophoric model AADPR.356. The main factor contributing the model AADPR.356 consists of two hydrogen bond acceptor groups, one hydrogen bond donor group, one positively charged group, and one aromatic ring group. Our developed model represents a statistically significant model with r2 value of 0.6801 and q2 value of 0.6731. Predicting the activity of the test set molecules provides a means for validating the QSAR model developed, and the activities predicted were in the range of the observed experimental activity values. Hence, our model represents a robust and statistical significant form which can be used to design better potential drugs that can target against CCR5 receptor.

The aim of the present work was to prepare, characterize and evaluate the solubility and dissolution behavior of ketoprofen co-crystals. Fusion method was employed for the preparation of ketoprofen co-crystals. The co-formers selected were cinnamic acid, glutaric acid, maleic acid, malonic acid, nicotinamide, oxalic acid, p-amino-benzoic acid, pamino salicylic acid, saccharin and urea. The prepared ketoprofen co-crystals were characterized by FT-IR, DSC and XRD. Ketoprofen co-crystals were evaluated for solubility and dissolution. Micromeritic properties were evaluated for cocrystal exhibiting higher solubility. A Shift in the IR peaks was observed for all the prepared co-crystals with no presence of additional peaks. DSC studies showed decrease in the heat of fusion from 257.74 to 50.39 J/g and melting point of drug from 95.80 to 73.57°C in the co-crystals. XRD peaks exhibited different peak patterns than peaks shown by the pure ketoprofen. All the preparations exhibited enhanced aqueous solubility as well as dissolution when compared with pure ketoprofen. Amongst the co-crystals prepared, Ketoprofen-p-Amino-salicylic acid co-crystals, exhibited 14 fold increases in aqueous solubility and in vitro release was found to be 93.41% in 60 mins. This work demonstrates the potential of cocrystallization by fusion as screening method for particle engineering. The results demonstrate the feasibility of pharmaceutical co-crystal design for ketoprofen.