The epidermal skin barrier protects the body from a host of daily challenges, providing protection against mechanical insults and the absorption of chemicals and xenobiotics. In addition to the physical barrier, the epidermis also presents an innate defense against microbial overgrowth. This is achieved through the presence of a diverse collection of microorganisms on the skin (the “microbiota”) that maintain a delicate balance with the host and play a significant role in overall human health. When the skin is wounded, the local tissue with a compromised barrier can become colonized and ultimately infected if bacterial growth overcomes the host response. Wound infections present an immense burden in healthcare costs and decreased quality of life for patients, and treatment becomes increasingly important because of the negative impact that infection has on slowing the rate of wound healing. In this review, we discuss specific challenges of treating wound infections and the advances in drug delivery platforms and formulations that are under development to improve topical delivery of antimicrobial treatments.

Chronic wounds are a significant and growing health problem, and clinical treatment is often a painful experience. A topical dosage form would be optimal to treat this pain. Poloxamer 407, a thermosensitive polymer that is a liquid at low temperatures but gels at higher temperatures, is well suited to administer topical analgesics to chronic wound sites. The goal of this study was to evaluate the gelation and drug delivery properties of poloxamer 407 gels containing diclofenac sodium for potential use in chronic wound analgesic delivery. The gelation properties of poloxamer formulations were evaluated rheologically. Drug delivery properties of poloxamers loaded with diclofenac sodium were evaluated using snakeskin dialysis membranes, intact porcine ear skin, and porcine ear skin impaired via tape stripping. A commercial gel product and a solution of diclofenac sodium in water were used as control formulations. Poloxamer concentration and gelation temperature varied inversely, and the addition of higher concentrations of diclofenac sodium correlated to significant increases in poloxamer gelation temperature. Poloxamer solutions were effective in limiting the permeation of diclofenac sodium through membranes with impaired barrier properties, and delivery of diclofenac sodium from poloxamer 407 did not vary significantly from delivery observed from the commercial gel product. The amount of drug delivered in 24 h did not change significantly with changes in poloxamer 407 concentration. The results of this study indicate that poloxamer 407 may be a useful formulation component for administration of an analgesic product to a chronic wound site.

In the skin, aging is associated with overall epidermal thinning, decreased barrier function and gradual deterioration of the epidermal immune response. However, the presence and role of cytokines, chemokines and biologic analytes (CCBAs) in immunosenescence are not known. Here we identified age-related changes in skin properties and CCBAs from stratum corneum of healthy human subjects, providing a means to utilize CCBAs as benchmarks for aging skin health. Transepidermal water loss and a(*) (skin redness) decreased in an age-dependent manner and were significantly lower (p < 0.05) in Groups 2 (56.6 ± 4.6 years) and 3 (72.9 ± 3.0 years) vs. Group 1 (24.3 ± 2.8 years). In skin wash fluid, 48 CCBAs were detected; seven were significantly lower (p < 0.05) in Groups 2 and 3: EGF, FGF-2, IFNα2, IL-1RA, HSA, keratin-6 and involucrin; cortisol was significantly higher (p < 0.05) in Groups 2 and 3. Our results correspond with the pro-inflammatory shift that occurs with immunosenescence and also provides basis for understanding the inflammatory changes in normal aging skin.

Background: Growing evidence suggests that pediatric palliative care (PPC) teams influence the care received by children and young adults with chronic, life-limiting illnesses. Little is known about how PPC involvement affects advance care planning (ACP) and circumstances of death in pediatric populations with a wide range of diagnoses. Objective: To determine the relationship between PPC involvement, ACP, and circumstances of death for pediatric patients. Design: A retrospective chart review of 558 pediatric patients who died between January 1, 2012 and December 31, 2016 was conducted. Descriptive statistics were used to characterize the sample. A multivariable logistic regression was used to obtain associations between PPC involvement and ACP. Setting: Large, multidisciplinary tertiary care center in a rural state. Measurements: Data abstracted for each patient included the following: demographic information, diagnosis, location of primary unit, hospice involvement, goals of care (GOC), code status, Physician Orders for Life-Sustaining Treatment (POLST) completion, and location of death. Results: Patients with PPC involvement were more likely to have had ACP addressed before death. After adjusting for covariates in the model, patients with PPC were more likely to have their GOC documented (odds ratio [OR] = 96.93), completion of POLST (OR = 24.06), do-not-resuscitate code status (OR = 7.71), and hospice involvement at the time of death (OR = 11.70) compared with those who did not receive PPC. Conclusions: Pediatric patients are more likely to have ACP addressed if they have PPC involvement. Patients with chronic complex conditions are most likely to receive palliative care.