Formulation of antiretroviral nanocrystals and development into a microneedle delivery system for potential treatment of HIV-associated neurocognitive disorder (HAND)

Folic Acid-Decorated Nanocrystals as Highly Loaded Trojan Horses to Target Cancer Cells

“…Importantly, the preparation of drug NCs using magnetically powered media milling stirring has been reported previously in the literature. Romero et al described the use of 2 mL vials to produce NCs, whereas work from our group reported the manufacture of drug NCs of various drugs including CUR using 10 mL vials. ,,− In this process, the movement of the magnetic bars and milling media leads to the impact, shear and compression forces, and particle breakage . Since the milling occurs in a solution of the surfactant, the newly created surfaces are quickly stabilized by the polymer/surfactant molecules that place their hydrophobic moieties on the NCs’ surface by electrostatic forces .…”

“…A similar case was reported by Abbate et al, where NCs of rilpivirine and cabotegravir were coated with chitosan. 28 This is crucial to this work, as the chitosan molecules stabilized on the NCs’ surface allowed further functionalization with FA as described in the following section.…”

“… 68 Research papers from this group, where drug NCs were loaded into dissolving microneedles, showed drug depots in the rats’ skin for up to 4 weeks. A report from Abbate et al 28 described an interesting approach, where microneedle-mediated delivery of positively charged rilpivirine and cabotegravir NCs led to drug accumulation in the central nervous system. Another work from Shen et al 18 demonstrated that integral quercetin NCs administered orally were detected in the plasma for up to 48 h. Once internalized by macrophages, NCs are located in the phagolysosome, from where the hydrophobic active eventually dissolves and permeates back to the cytosol and then back to the plasma, modifying the pharmacokinetic performance of the drug.…”

“…A media milling technique utilizing an ultrasmall-system assembly that was previously reported was applied to prepare NCs, with minor changes. ,,− Chitosan (CS) in combination with TPGS was used to stabilize the NCs (CS-NCs), which enabled to have −NH 2 groups available on the NCs’ surface for subsequent drafting with FA, as detailed in the following section. To obtain the NCs, 100 mg of CUR, 5 mL of 0.5% w/v TPGS, and 3 mL of 0.1, 0.2, or 0.4% w/v CS were added into a 12 mL glass vial together with 3 mL of yttria-stabilized zirconia beads and two magnetic stirring bars of 25 × 8 mm (IKAFLON, IKA, Staufen, Germany).…”

Polymer Delivery Systems for Long-Acting Antiretroviral Drugs

“…Although varying compositions of RPV nanocrystal suspension and PVP were used to manufacture MNs, the MNs with 70% RPV, 15% PVP, and 15% water demonstrated better plasma RPV levels compared to other MNs. Due to the discreet nature of the MNs and their ability for localized delivery of drugs, the same type of RPV MN was also generated by the same group for vaginal and CNS delivery of RPV [ 228 , 229 ].…”