Chiral Nanosilica Drug Delivery Systems Stereoselectively Interacted with the Intestinal Mucosa to Improve the Oral Adsorption of Insoluble Drugs

Abstract

Chiral nanoparticles (NPs) with nanoscale rough surfaces have enormous application prospects in drug delivery. However, the stereoselective interactions between the chiral NPs and biosurfaces remain challenging and mysterious. Herein, we designed mesoporous silica nanocarriers (l/d/dl-TA-PEI@CMSN) exhibiting the same structural parameters (hydrophilic, electroneutral, spherical NPs, ∼120 nm) but different geometrical chirality as oral nanodrug delivery systems (Nano-DDS) for insoluble drugs nimesulide (NMS) and ibuprofen (IBU) and demonstrated their stereoselective interactions with the intestinal mucosa, that is, l-TA-PEI@CMSN as well as Nano-DDS in the l-configuration displayed apparent superior behaviors in multiple microprocesses associated with oral adsorption, including adhesion, penetration, adsorption, retention and uptake, causing by the stereomatching between the chiral mesostructures of NPs and the inherent chiral topologies of the biosurfaces. As hosting systems, l/d/dl-TA-PEI@CMSN effectively incorporated drugs in amorphous states and helped to overcome the stability, solubility and permeability bottlenecks of drugs. Subsequently, Nano-DDS in the l-configuration (including IBU/l-TA-PEI@CMSN and NMS/d-TA-PEI@CMSN owing to a chiral inversion) showed higher oral delivery efficiency of NMS and IBU evidenced by the larger relative bioavailability (1055.06% and 583.17%, respectively) and stronger anti-inflammatory and analgesic effects. In addition, l/d/dl-TA-PEI@CMSN were stable, nonirritative, biocompatible and biodegradable, benefiting for their clinical applications. These findings provided insights into the rational design of functionalized Nano-DDS and contributed to the further knowledge in the field of chiral pharmaceutical science.

Acid-Responsive Macroporous Silica Nanoparticles for Bcl-2-Functional-Converting Peptide Release and Synergism with Celastrol for Enhanced Therapy against Resistant Cancer

“…One was synthesizing various Ce derivatives. The other was constructing drug nanocarriers to enhance the efficiency and reduce the undesired toxic and side effects . Different from the ones mentioned above, we tried to use low doses of Ce in combination with protein/peptide nanodrugs to combat drug-resistant tumors.…”

“…The other was constructing drug nanocarriers to enhance the efficiency and reduce the undesired toxic and side effects. 38 Different from the ones mentioned above, we tried to use low doses of Ce in combination with protein/peptide nanodrugs to combat drug-resistant tumors. The low and safe concentration of free Ce for the cellular experiments was determined based on not only our previous report that was below 2 μM (∼1 μg/mL) 18 but also the sensitivity to different cancer cell lines.…”

pH-Sensitive Biomimetic Nanosystem Based on Large-Pore Mesoporous Silica Nanoparticles with High Hyaluronidase Loading for Tumor Deep Penetration

“…Among various kinds of nanocarriers, mesoporous silica nanoparticles (MSNs) have attracted great interest on account of their biocompatibility, high surface area and pore volume, composition modifiability, size adjustability, chirality adjustability, and surface engineering ability. , MSNs have been functionalized with Hyal for enhanced chemo-immunotherapy. However, until now there are very few reports , of loading Hyal in MSNs for tumor deep penetration.…”

“…However, until now there are very few reports , of loading Hyal in MSNs for tumor deep penetration. Hyal has a large size (60 kDa, ∼6 nm diameter) and negative surface charges (PI: 5–6) in neutral solutions . For effective loading Hyal, MSNs with large pore sizes are beneficial and prerequisite.…”

“…Hyal has a large size (60 kDa, ∼6 nm diameter) and negative surface charges (PI: 5−6) in neutral solutions. 14 For effective loading Hyal, MSNs with large pore sizes are beneficial and prerequisite. In addition, positively charged MSNs should be able to facilitate Hyal loading through electrostatic interactions.…”