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Side effects and acquired resistance by cancer cells limit the use of platinum anticancer drugs. Modification of oxaliplatin (OXA) into a lipophilic Pt(IV) complex [Pt(DACH)(OAc)(OPal)(ox)] (1), containing both lipophilic and hydrophilic axial ligands, was applied to improve performance and facilitate incorporation into polymeric nanoparticles. Complex 1 exhibited unique potency against a panel of cancer cells, including cisplatin-resistant tumor cells. [Pt(DACH)(OAc)(OPal)(ox)] incorporated nanoparticles (2) presented a mean diameter of 146 nm with encapsulation yields above 95% as determined by HPLC. Complexes 1 and 2 showed enhanced in vitro cellular Pt accumulation, DNA platination, and antiproliferative effect compared to OXA. Results of an orthotopic intraperitoneal model of metastatic ovarian cancer (SKOV-3) and a xenograft subcutaneous model of colon (HCT-116) tumor in SCID-bg mice showed that the activity of 1 and 2 significantly decreased tumor growth rates compared to control and OXA treatment groups. Consequently, these findings warrant further development toward clinical translation.

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Intranasal drug administration is considered a routine in the treatment of many nasal conditions including chronic rhinosinusitis (CRS), which is a common disease involving long-term inflammation of the nasal mucosa. Topical nasal steroid treatment is safe and easy to use and plays a basic role in both nonsurgical and surgical treatments for CRS. Intranasal steroid therapy for various time intervals is commonly used before and after endoscopic CRS nasal surgeries to reduce inflammation and edema and to improve mucosal healing. The medication is currently administered via conventional nasal sprays; therefore, there is an incentive to develop more efficient drug delivery systems for the controlled release of topical steroids into the sinonasal cavities over a prolonged period of time. In this study, poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with mometasone furoate (MF) were generated using the nanoprecipitation method and characterized physicochemically and morphologically. MF NPs exhibited adequate physicochemical properties and high drug encapsulation efficiency and loading content. MF exhibited sustained release from NPs over 7 days in vitro with an initial burst release; various mathematical models were applied to determine the kinetics of drug release. Having demonstrated the ability to load MF in PLGA-NPs using the nanoprecipitation method for the first time, these NPs urge the need for additional investigations to demonstrate their therapeutic potential in nasal delivery applications.

Drug delivery through the skin has immense advantages compared to other routes of administration and offers an optimal way to treat inflammatory skin diseases, where corticosteroids are the cornerstone of topical therapy. Still, their therapeutic efficiency is limited due to inadequate skin permeability, potential side effects, and reduced patient compliance. To overcome these drawbacks, we propose a drug delivery system consisting of dexamethasone (DEX)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) incorporated in sodium alginate (SA) microneedles (MNs) as a minimally invasive dosage form for controlled drug release. Drug-loaded PLGA NPs were prepared by a nanoprecipitation method with a high encapsulation yield. They exhibited a controlled release pattern over 120 h. A modified vacuum-deposition micromolding method was used to load the obtained DEX-NPs into the tips of dissolving MNs. The NP-MNs showed improved insertion capabilities into the skin-simulant parafilm model and enhanced mechanical strength when tested against different static forces compared to their counterparts (SA-MNs). The results of an MN dissolution study following application to ex vivo chicken skin and agarose gel indicate that the NP-loaded segments of MNs dissolve within 15 s, in which the NPs are released into the skin. Taken together, the incorporation of DEX-NPs into SA-MNs could be a promising approach to bypass the limitations of conventional topical treatment of skin diseases, allowing for self-administration, increased patient compliance, and controlled drug release.

Background: upper airway complications are common sequelae of endotracheal tube (ETT) intubation, and systemic corticosteroids are considered a mainstay treatment for this problem. Drug-eluting ETT may present an attractive option for topical steroid delivery while avoiding systemic side effects and improving the therapeutic outcome. The objective of the present study is to evaluate the reduction of tube-related tracheal morbidity via a self-designed steroid-eluting ETT with controlled sustained release properties in an animal model. Methods: steroideluting ETTs were coated by poly(lactic-co-glycolic acid) -electrospun nanofibers loaded with mometasone furoate (MF) as a model drug. Animals were randomly assigned into three equal groups: non-intubated, blank-ETT, and loaded-ETT. The intubation interval was 1 week. Specimens were analyzed by histology, specific fibrosis staining, and scanning electron microscopy (SEM). Results: the blank-ETT group exhibited a significant increase in tracheal mucosal thickness compared to the loaded-ETT and control groups. Average tracheal mucosal thickness was 112 ± 34, 242 ± 49, and 113 ± 43 μm in the control, blank-ETT, and loaded-ETT groups, respectively. The blank-ETT group exhibited a significant increase in tracheal fibrosis compared to the loaded-ETT and control groups. Relative fibrosis values were 0.07 ± 0.05, 0.154 ± 0.1, and 0.0984 ± 0.084% for the control, blank-ETT, and loaded-ETT groups, respectively. While SEM imaging showed normal surface structures in the control group, intubated blank-ETT rats showed severe surface structural damage, whereas only mild damage was observed in the loaded-ETT group. Conclusions: local sustained release of MF via a self-designed drug-eluting ETT is a potential therapeutic approach which may significantly reduce tuberelated upper airway morbidity.

Transdermal drug delivery systems are a useful and minimally invasive alternative to other drug administration routes. Biodegradable polymeric microneedles (MNs) are widely used in controlled‐release drug delivery due to their...