Development of antimicrobial coating by layer-by-layer [corrected] dip coating of chlorhexidine-loaded micelles.

Layer-by-layer (LbL) dip coating, accompanying with the use of micelle structure, allows hydrophobic molecules to be coated on medical devices' surface via hydrogen bonding interaction. In addition, micelle structure also allows control release of encapsulated compound. In this research, we investigated methods to coat and maximize the amount of chlorhexidine (CHX) on silicone surface through LbL dip coating method utilizing hydrogen bonding interaction between PEG on micelle corona and PAA. The number of coated cycles was varied in the process and 90 coating cycles provided the maximum amount of CHX loaded onto the surface. In addition, pre-coating the surface with PAA enhanced the amount of coated CHX by 20%. Scanning electron microscope (SEM) and Fourier Transform Infrared Spectroscopy (FTIR) were used to validate and characterize the coating. For control release aspect, the coated film tended to disrupt at physiological condition; hence chemical crosslinking was performed to minimize the disruption and maximize the release time. Chemical crosslinking at pH 2.5 and 4.5 were performed in the process. It was found that chemical crosslinking could help extend the release period up to 18 days. This was significantly longer when compared to the non-crosslinking silicone tube that could only prolong the release for 5 days. In addition, chemical crosslinking at pH 2.5 gave higher and better initial burst release, release period and antimicrobial properties than that of pH 4.5 or the normal used pH for chemical crosslinking process.

Preparation and evaluation of blend polymer films for wound dressing using vancomycin-loaded polycaprolactone and carboxymethyl cellulose via crosslinking methods: Effect of mechanical strength, antibacterial activity, and cytotoxicity.

Polycaprolactone (PCL) and carboxymethyl cellulose (CMC) are two materials with beneficial properties for wound healing applications. Here, the simple preparation of PCL/CMC polymer films via the crosslinking method was demonstrated for the first time. The polymer films represented the suitable properties of liquid absorption and tensile strength to be used as a wound dressing. The blend polymer films can also load the vancomycin, which prolongs the drug release for effectiveness against S. aureus. The trifluoroethanol showed less toxicity in comparison with other crosslinking agents. This process can also be applied further in other medical devices and wound healing applications.

Investigating silver nanoparticles and resiquimod as a local melanoma treatment.

Over the last decade, the potential for silver nanoparticles (AgNP) to be used as an anti-melanoma agent has been supported by both in vitro and in vivo evidence. However, an undesirably high concentration of AgNP is often required to achieve an antitumor effect. Therefore a combination treatment that can maintain or improve antitumor efficacy (with lower amounts of AgNP) while also reducing off-target effects is sought. In this study, the combination of AgNP and resiquimod (RSQ: a Toll-like receptor agonist) was investigated and shown to significantly prolong the survival of melanoma-challenged mice when added sequentially. Results from toxicity studies showed that the treatment was non-toxic in mice. Immune cell depletion studies suggested the possible involvement of CD8+ T cells in the antitumor response observed in the AgNP + RSQ (sequential) treatment. NanoString was also employed to further understand the mechanism underlying the increase in the treatment efficacy of AgNP + RSQ (sequential); showing significant changes, compared to the naive group, in gene expression in pathways involved in apoptosis and immune stimulation. In conclusion, the combination of AgNP and RSQ is a new combination worthy of further investigation in the context of melanoma treatment.

Anti-melanoma Effects of Resiquimod (RSQ) In Vitro and in Combination with Immune Checkpoint Blockade In Vivo.

Melanoma is the deadliest form of skin cancer and surgery is currently the most effective treatment. However, there are situations where surgery fails or is not an option to treat melanoma patients. Immunotherapy such as immune checkpoint blockade (e.g., anti-PD-1) can be effective as an alternative treatment for melanoma patients; however, the percentage of melanoma patients that exhibit complete responses from anti-PD-1 monotherapy is low, and a hostile immunosuppressive tumor microenvironment may be at least partly responsible. Resiquimod (RSQ) is an imidazoquinolinamine derivative and TLR-7/8 agonist that could enhance the antitumor activity of immune checkpoint blockade when these agents are combined as a treatment for melanoma. Here, the effect of combining systemic anti-PD-1 and locally administered RSQ on the survival of melanoma-challenged mice was tested. Our results demonstrated that anti-PD-1 in combination with RSQ can significantly prolong the survival of melanoma-challenged mice, compared to untreated mice and mice treated with anti-PD-1 alone. In addition, the in vitro studies showed that RSQ can mediate a direct anti-proliferative effect on melanoma cells. In conclusion, the combination of RSQ and anti-PD-1 may be a promising treatment for melanoma patients, especially as both treatments have already been used independently to safely treat melanoma patients.

Topically Applied Resiquimod versus Imiquimod as a Potential Adjuvant in Melanoma Treatment.

Melanoma is the most lethal form of skin cancer and surgery remains the preferred and most effective treatment. Nevertheless, there are cases where surgery is not a viable method and alternative treatments are therefore adopted. One such treatment that has been tested is topical 5% imiquimod (IMQ) cream, which, although showing promise as a treatment for melanoma, has been found to have undesirable off-target effects. Resiquimod (RSQ) is an immunomodulatory molecule that can activate immune responses by binding to Toll-like receptors (TLR) 7 and 8 and may be more effective than IMQ in the context of melanoma treatment. RSQ can cross the stratum corneum (SC) easily without requiring pretreatment of the skin. In a gel formulation, RSQ has been studied as a monotherapy and adjuvant for melanoma treatment in pre-clinical studies and as an adjuvant in clinical settings. Although side effects of RSQ in gel formulation were also reported, they were never severe enough for the treatment to be suspended. In this review, we discuss the potential use of RSQ as an adjuvant for melanoma treatment.

Skin Penetration Enhancement Strategies Used in the Development of Melanoma Topical Treatments.

Malignant melanoma is an aggressive form of skin cancer for which there is currently no reliable therapy and is considered one of the leading health issues in the USA. At present, surgery is the most effective and acceptable treatment; however, surgical excision can be impractical in certain circumstances. Topical skin delivery of drugs using topical formulations is a potential alternative approach which can have many advantages aside from being a non-invasive delivery route. Nevertheless, the presence of the stratum corneum (SC) limits the penetration of drugs through the skin, lowering their treatment efficacy and raising concerns among physicians and patients as to their effectiveness. Currently, research groups are trying to circumvent the SC barrier by using skin penetration enhancement (SPE) strategies. The SPE strategies investigated include chemical skin penetration enhancers (CPEs), physical skin penetration enhancers (PPEs), nanocarrier systems, and a combination of SPE strategies (cream). Of these, PPEs and cream are the most advanced approaches in terms of preclinical and clinical studies, respectively.