Drug Delivery and Development of Anti-HIV Microbicides by José das Neves, Bruno Sarmento

By José das Neves, Bruno Sarmento

The around the globe influence of HIV/AIDS is easily famous. This e-book presents for the 1st time an intensive and demanding evaluate of present points, contemporary advancements, and tendencies within the formula and drug supply touching on anti-HIV microbicides via top scientists within the box. also, pertinent regulatory features and socioeconomical matters relating to the topic are mentioned. within the absence of a medication, prophylaxis represents a cornerstone within the conflict opposed to an infection. One promising approach includes the use round the time of sexual activity of vaginal/rectal items containing antiviral compounds, termed microbicides. it really is now well-known that categorical improvement of drug dosage varieties and/or drug supply structures is an fundamental point for the luck of microbicides. assorted teams strived during the last decade to optimize the biophysical and technological functionality of conventional dosage varieties (gels, drugs, and suppositories) to meet the specificities of microbicides use, with no neglecting clients’ personal tastes and affordability matters. in addition, new formula methods, reminiscent of vaginal jewelry and movies, nanotechnology-based structures, stimuli-sensitive formulations, detailed drug supply structures, between others were proposed and are at present present process pre-clinical or perhaps scientific trying out.

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4â•… RNA-Based Aptamer Microbicides Aptamers are single-stranded synthetic oligonucleotides that are selected from random sequences and then expose them to the target bits of protein to identify the tight-binding RNA sequences [151]. Repeated rounds of the process—known as in vitro selection or systematic evolution of ligands by exponential enrichment—can yield aptamers with improved affinities for their targets [152,153]. The ability of aptamers to fold into a variety of complex, sequencespecific tertiary conformations enables them to bind a wide range of targets and rival antibodies in their potential diversity.

Aptamer-siRNA chimeras efficiently transfect and knockdown gene expression in cells bearing the surface receptor recognized by the aptamer. Fusion of an anti-HIV tat/rev siRNA to an aptamer directed to the surface gp120 protein on HIV-infected cells has led to cell type-specific delivery of the siRNA [158]. The antiviral activity of aptamer was enhanced by aptamer-mediated delivery of an anti-HIV-delivered siRNA. Chimeric-siRNAs containing an aptamer that recognizes HIV-gp120 inhibit HIV replication in already infected cells in vitro and in vivo [157–160].

Typical processing temperatures for creating polymeric elastomeric devices range from 130 to 190°C [200]. Therefore, ARVs incorporated within the device need to be stable under these conditions, at least for several minutes while the drug is being compounded into the polymer melt and then processed to form the final device. The high solubility of hydrophobic drug substances in the polymer at the high melt extrusion temperature creates an amorphous dosage form that is potentially thermodynamically unstable and may undergo an amorphous to crystalline transformation.

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