Highly active antiretroviral (ARV) therapy (HAART) for chronic suppression of HIV replication has revolutionized the treatment of HIV/AIDS. HAART is no panacea; treatments must be maintained for life. Although great progress has been made in ARV therapy, HIV continues to replicate in anatomical and intracellular sites where ARV drugs have restricted access. Nanotechnology has been considered a platform to circumvent some of the challenges in HIV/AIDS treatment. Dispersion polymerization was used to fabricate two types (PMM and ECA) of polymeric nanoparticles, and each was successfully loaded with four ARV drugs (zidovudine, lamivudine, nevirapine, and raltegravir), followed by physicochemical characterization: scanning electron microscope, particle size, zeta potential, drug loading, and in vitro availability. These nanoparticles efficiently inhibited HIV-1 infection in CEM T cells and peripheral blood mononuclear cells; they hold promise for the treatment of HIV/AIDS. The ARV-loaded nanoparticles with polyethylene glycol on the corona may facilitate tethering ligands for targeting specific receptors expressed on the cells of HIV reservoirs.

Quality by design (QbD) in the pharmaceutical industry involves designing and developing drug formulations and manufacturing processes which ensure predefined drug product specifications. QbD helps to understand how process and formulation variables affect product characteristics and subsequent optimization of these variables vis-à-vis final specifications. Statistical design of experiments (DoE) identifies important parameters in a pharmaceutical dosage form design followed by optimizing the parameters with respect to certain specifications. DoE establishes in mathematical form the relationships between critical process parameters together with critical material attributes and critical quality attributes. We focused on the fabrication of biodegradable nanoparticles by dispersion polymerization. Aided by a statistical software, d-optimal mixture design was used to vary the components (crosslinker, initiator, stabilizer, and macromonomers) to obtain twenty nanoparticle formulations (PLLA-based nanoparticles) and thirty formulations (poly-ɛ-caprolactone-based nanoparticles). Scheffe polynomial models were generated to predict particle size (nm), zeta potential, and yield (%) as functions of the composition of the formulations. Simultaneous optimizations were carried out on the response variables. Solutions were returned from simultaneous optimization of the response variables for component combinations to (1) minimize nanoparticle size; (2) maximize the surface negative zeta potential; and (3) maximize percent yield to make the nanoparticle fabrication an economic proposition.

Genetic imprinting: the parent of origin-specific biased expression of alleles is an important type of epigenetic gene regulation in flowering plants and mammals. All imprinted genes show either maternal -or paternal-specific mono-allelic expression. Considering that plants and mammals shared a common ancestor more than one billion years ago, significant overlap and potentially equally significant differences in the genomic imprinting mechanisms in these two taxa are emerging. In plants, the imprinted genes are primarily imprinted in the ephemeral endosperm tissues of the seeds which do not contribute any genome to future generations, while in mammals, the imprinted genes are located in embryo, placenta, and the adult body. Though both kingdoms silence imprinted genes using DNA methylation, imprinted alleles in mammals are targeted for silencing while in plants preexisting methylation is specifically removed from the allele destined to be active in maternally expressed genes in the endosperm. It is now accepted that imprinting evolved in both taxa due to competition between parental genomes over resource allocation to offspring. Moreover, the distinct life cycle stages between the taxa may account for the different strategies used by plants and mammals to regulate parent-specific gene expression. The elucidation of the genetic basis and molecular mechanisms responsible for genetic imprinting have provided answers to various crucial questions arising in biological sciences.