Laminated holmium-166-containing electrospun bandages for use against skin cancer.

The number of non-melanoma skin cancer (NMSC) cases in the US will increase significantly over the next decade due to a rise in UV exposure. One of the treatment methods used to remove NMSC lesions is radiation therapy. The two types of radiation therapy used in the clinic are external beam therapy and brachytherapy. However, both require specialized on-site instrumentation and for patients to remain immobile. In this work, we studied an alternative radiation therapy - one that does not require expensive on-site equipment and would allow for enhanced patient mobility and, thus, comfort. We prepared sealed source, nylon-laminated holmium-166-containing radiotherapeutic bandages and used them in C3H/HeN mice with murine SCCVII tumor grafts. Overall, tumor sizes were smallest when treated with therapeutically relevant radiation doses via radiotherapeutic bandages (compared to controls), and no histological evidence of toxicity to tissues was observed. Thus, our optimized radiotherapeutic bandage offers a flexible approach to treating NMSC.

Preparation and Optimization of an Ultraflexible Liposomal Gel for Lidocaine Transdermal Delivery.

The pain caused by lidocaine injections into the face prior to facial plastic surgeries intended to remove growths or tumorous lesions has been reported by many patients to be the worst part of these procedures. However, the lidocaine gels and creams currently on the market do not deliver an equal or better local anesthetic effect to replace these injections. To develop an alternative to the painful local anesthetic injection, we prepared ultraflexible liposomes using soy phosphatidylcholine, lidocaine, and different amounts of sodium cholate, a surfactant. The prepared ultraflexible liposomes (UFLs) were examined for particle size, zeta potential, cytotoxicity, and in vitro release. By using a carbomer as a gelling agent, the prepared UFL lidocaine gels were evaluated for their penetration ability in a Franz diffusion cell, using Strat-M membranes. The formulation achieving the highest amount of penetrated lidocaine was chosen for further pH, viscosity, and stability tests. The local anesthetic efficacy of the formulation was investigated by an in vivo tail-flick test in rats. Our findings suggested that this topical gel formulated with ultraflexible liposomal lidocaine has enhanced skin permeation ability, as well as an improved local analgesic effect from the lidocaine.

Optimization of DOTAP/chol Cationic Lipid Nanoparticles for mRNA, pDNA, and Oligonucleotide Delivery.

Lipid nanoparticles (LNPs) can be used as delivery vehicles for nucleic acid biotherapeutics. In fact, LNPs are currently being used in the Pfizer/BioNTech and Moderna COVID-19 vaccines. Cationic LNPs composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (chol) LNPs have been classified as one of the most efficient gene delivery systems and are being tested in numerous clinical trials. The objective of this study was to examine the effect of the molar ratio of DOTAP/chol, PEGylation, and lipid to mRNA ratio on mRNA transfection, and explore the applications of DOTAP/chol LNPs in pDNA and oligonucleotide transfection. Here we showed that PEGylation significantly decreased mRNA transfection efficiency of DOTAP/chol LNPs. Among non-PEGylated LNP formulations, 1:3 molar ratio of DOTAP/chol in DOTAP/chol LNPs showed the highest mRNA transfection efficiency. Furthermore, the optimal ratio of DOTAP/chol LNPs to mRNA was tested to be 62.5 µM lipid to 1 µg mRNA. More importantly, these mRNA-loaded nanoparticles were stable for 60 days at 4 °C storage without showing reduction in transfection efficacy. We further found that DOTAP/chol LNPs were able to transfect pDNA and oligonucleotides, demonstrating the ability of these LNPs to transport the cargo into the cell nucleus. The influence of various factors in the formulation of DOTAP/chol cationic LNPs is thus described and will help improve drug delivery of nucleic acid-based vaccines and therapies.

3D Printing and Dissolution Testing of Novel Capsule Shells for Use in Delivering Acetaminophen.

Individualized drug delivery improves drug efficacy and safety for patients. To implement individualized drug delivery, patient-specific tailored dosages produced on a small scale are needed. However, current pharmaceutical manufacturing is not suitable for personalized dosage forms. Although convenient to deliver various drugs, current gelatin capsules using animal collagen protein have many limitations, such as releasing drugs too fast and incompatibility with some diets. In contrast, 3D printed capsules have great potential to advance individualized treatments. In this paper, we 3D printed and tested non-animal-based capsule shells for the delivery of acetaminophen. Capsule shells were composed of poly(vinyl) alcohol (PVA) and PVA blends with 5-25% hydroxypropyl methylcellulose (HPMC). Dissolution of acetaminophen when delivered in -hese capsule shells was tested using a USP dissolution test apparatus 2 (paddle type) at gastric pH. The novel shells were compared to each other and to commercially available hard gelatin capsules. Dissolution results show that acetaminophen when delivered in 3D printed capsules was slower than when delivered by gelatin capsules. Increasing the percentage of HPMC in the blend further delayed its release and dissolution. This delay could potentially increase the efficacy and reduce the side effects of acetaminophen. These shells also offer a non-animal-based alternative to gelatin capsules. Furthermore, 3D printing of capsule shells with specific polymer blends may be useful for patient-specific therapy in compounding pharmacies across the country.

Phenethyl Isothiocyanate-Containing Carbomer Gel for Use against Squamous Cell Carcinoma.

It is currently estimated that one in every five Americans will develop skin cancer during their lifetime. Squamous cell carcinoma (SCC) is a common type of skin cancer that can develop due to the skin's exposure to the sun. Herein, we prepared a topical gel containing 0.5% v/w phenethyl isothiocyanate (PEITC) for the treatment of SCC. PEITC is a naturally occurring isothiocyanate that has been shown to have efficacy against various types of cancer in preclinical studies. We first incorporated PEITC into a carbomer gel. A uniform formulation was prepared, and its viscosity was appropriate for topical application. We then demonstrated the release of PEITC from the gel into and through a Strat-M skin-like membrane. Finally, the effects of the PEITC-containing gel were tested against SCC and normal keratinocytes skin cells in culture, and these results were compared to those obtained for free 5-fluoruracil (5-FU), a commonly used skin-cancer drug. Our results show that a homogeneous PEITC-containing topical gel can be prepared and used to kill SCC cells. Thus, our formulation may be useful for treating SCC in the clinic.