Bioinspired synthesis of bioactive glass nanocomposites for hyaluronic acid delivery to bone and skin.

In this study, we present nanocomposites of bioactive glass (BG) and hyaluronic acid (HA) (nano-BGHA) for effective delivery of HA to skin and bone. The synthesis of the nanocomposites has been carried out through the bio-inspired method, which is a modification of the traditional Stober's synthesis as it avoids using ethanol, ammonia, synthetic surfactants, or high-temperature calcination. This environmentally friendly, bio-inspired route allowed the synthesis of mesoporous nanocomposites with an average hydrodynamic radius of ∼190 nm and an average net surface charge of ∼-21 mV. Most nanocomposites are amorphous and bioactive in nature with over 70 % cellular viability for skin and bone cell lines even at high concentrations, along with high cellular uptake (90-100 %). Furthermore, the nanocomposites could penetrate skin cells in a transwell set-up and artificial human skin membrane (StratM®), thus depicting an attractive strategy for the delivery of HA to the skin. The purpose of the study is to develop nanocomposites of HA and BG that can have potential applications in non-invasive treatments that require the delivery of high molecular weight HA such as in the case of osteoarthritis, sports injury treatments, eye drops, wound healing, and some anticancer treatments, if further investigated. The presence of BG further enhances the range to bone-related applications. Additionally, the nanocomposites can have potential cosmeceutical applications where HA is abundantly used, for instance in moisturizers, dermal fillers, shampoos, anti-wrinkle creams, etc.

Albumin Nanoparticles Surface Decorated with a Tumor-Homing Peptide Help in Selective Killing of Triple-Negative Breast Cancer Cells.

In this article, we describe a method of delivery of doxorubicin using a novel tumor-homing peptide-based albumin nanoparticle system to triple-negative breast cancer cells (TNBC). The absence and reduced expression of the hormone (estrogen, progesterone) and HER2 (human epidermal growth factor 2) receptors, respectively, render TNBC patients nonsusceptible to different available targeted therapies. These peptide-modified nanoparticles could be taken up by TNBC cells more effectively than their bare counterparts. The drug-loaded peptide-modified nanoparticles achieved an optimal but crucial balance between cell killing in cancerous cells and cell survival in the noncancerous ones. This appears to be because of different routes of entry and subsequent fate of the bare and peptide-modified nanoparticles in cancerous and noncancerous cells. In a TNBC mouse model, the peptide-modified system fared better than the free drug in mounting an antitumor response while not being toxic systemically.

Surface-Engineered Mucus Penetrating Nucleic Acid Delivery Systems with Cell Penetrating Peptides for the Lungs.

Nucleic acids, both DNA and small RNAs, have emerged as potential therapeutics for the treatment of various lung disorders. However, delivery of nucleic acids to the lungs is challenging due to the barrier property imposed by mucus, which is further reinforced in disease conditions such as chronic obstructive pulmonary disease and asthma. The presence of negatively charged mucins imparts the electrostatic barrier property, and the mesh network structure of mucus provides steric hindrance to the delivery system. To overcome this, the delivery system either needs to be muco-inert with a low positive charge such that the interactions with mucus are minimized or should have the ability to transiently dismantle the mucus structure for effective penetration. We have developed a mucus penetrating system for the delivery of both small RNA and plasmid DNA independently. The nucleic acid core consists of a nucleic acid (pDNA/siRNA) and a cationic/amphipathic cell penetrating peptide. The mucus penetrating coating consists of the hydrophilic biopolymer chondroitin sulfate A (CS-A) conjugated with a mucolytic agent, mannitol. We hypothesize that the hydrophilic coating of CS-A would reduce the surface charge and decrease the interaction with negatively charged mucins, while the conjugated mannitol residues would disrupt the mucin-mucin interaction or decrease the viscosity of mucus by increasing the influx of water into the mucus. Our results indicate that CS-A-mannitol-coated nanocomplexes possess reduced surface charge, reduced viscosity of artificial mucus, and increased diffusion in mucin suspension as well as increased penetration through the artificial mucus layer as compared to the non-coated ones. Further, the coated nanocomplexes showed low cytotoxicity as well as higher transfection in A-549 and BEAS-2B cells as compared to the non-coated ones.