Chemotherapeutic loading via tailoring of drug-carrier interactions in poly (sialic acid) micelles

New methods in nanoparticle development have aimed to develop customized carriers suited for specific purposes. Micelles, due to their highly tailorable nature, are prime candidates for this customizable methodology. In order to maximize drug loading and tailor release, groups of the micelle core should be carefully selected in order to exploit inherent interactions between the selected drug and the carrier core. Small variations within the composition of these groups can greatly affect micelle characteristics (e.g., size, stability, loading and release). While covalent bonding of drug-to-carrier has enhanced drug loading, drawbacks include inhibited release and altered drug properties. As a result, drug/carrier non-covalent interactions such as hydrophobic attraction, hydrogen bonding and π-π stacking have all garnered great interest, allowing for both enhanced loading as well as bond dissociation to aid in drug release. Just as important, external composition of these micelles should be suited for specific therapeutic applications. Examples include providing stabilization, enhanced circulation times and site-specific targeting. Poly (sialic acid) (PSA), a naturally occurring polysaccharide, has been shown to exhibit all three of these properties yet remains relatively unexplored in the field of micelle-based cancer drug delivery applications. Here, we have grafted various phenyl-terminated alkyl groups (PTAGs) onto the backbone of PSA (PTAG-g-PSA), each selected in order to exploit a specific non-covalent interaction (hydrophobic attraction, hydrogen bonding and π-π stacking) between the PTAG group and the anthracycline chemotherapeutic doxorubicin (DOX) (Figure 1). Upon aqueous self-assembly, these amphiphiles formed micelles which exhibited variation in size, stability, cytotoxicity and DOX loading/release based upon the PTAG selected. For example, PTAGs selected to exploit either hydrogen bonding or π-π stacking loaded in a similar fashion yet varied greatly in release properties. Therefore, the synergistic effect of these small-scale modifications in core groups selected can greatly effect micelle characteristics and result in highly tailorable carriers

Supra-Pubic Single Incision Cholecystectomy

Surgery is moving towards less invasive and cosmetically superior approaches such as single incision laparoscopy (SIL). While trans-umbilical SIL is gaining popularity, incisions may lead to post-operative deformations of the umbilicus and the possibility of an increased rate of incisional hernias. Access within the pubic hairline allows preservation of the umbilicus and results in a scar which is concealed within the pubic hair. Supra-pubic single incision cholecystectomy was performed in a 30-year-old patient with symptomatic gallstones. A 2.5-cm transverse incision was placed within the pubic hairline and a subcutaneous tunnel was formed. Three 5-mm ports were introduced into the tunnel and perforated the anterior rectus sheath superior to the skin incision. The surgical procedure was then undertaken with conventional laparoscopic instrumentation. The adjacent 5-mm incisions were merged for gallbladder removal. The entry site was closed under direct vision. The above procedure was technically feasible and without complication. Operative time was 45 min, and the patient was discharged 5 h post-operatively. Supra-pubic single incision laparoscopic cholecystectomy may offer a more cosmetically appealing result than standard umbilical access. The operation can be performed by surgeons skilled in single incision techniques with good result

Supra-Pubic Single Incision Cholecystectomy

Surgery is moving towards less invasive and cosmetically superior approaches such as single incision laparoscopy (SIL). While trans-umbilical SIL is gaining popularity, incisions may lead to post-operative deformations of the umbilicus and the possibility of an increased rate of incisional hernias. Access within the pubic hairline allows preservation of the umbilicus and results in a scar which is concealed within the pubic hair. Supra-pubic single incision cholecystectomy was performed in a 30-year-old patient with symptomatic gallstones. A 2.5-cm transverse incision was placed within the pubic hairline and a subcutaneous tunnel was formed. Three 5-mm ports were introduced into the tunnel and perforated the anterior rectus sheath superior to the skin incision. The surgical procedure was then undertaken with conventional laparoscopic instrumentation. The adjacent 5-mm incisions were merged for gallbladder removal. The entry site was closed under direct vision. The above procedure was technically feasible and without complication. Operative time was 45 min, and the patient was discharged 5 h post-operatively. Supra-pubic single incision laparoscopic cholecystectomy may offer a more cosmetically appealing result than standard umbilical access. The operation can be performed by surgeons skilled in single incision techniques with good result