Subcutaneous hydration and medications infusions (effectiveness, safety, acceptability): A systematic review of systematic reviews.

OBJECTIVE: To synthesize the current evidence for subcutaneous hydration and medication infusions from systematic reviews and to assess their methodological quality. INTRODUCTION: Peripheral intravascular cannula/catheter insertion is a common invasive procedure for administering fluids and medications. Venous depletion is a growing concern for several patient populations. Subcutaneous access for the administration of isotonic solutions and medications is an alternative; however, vascular access assessment and planning guidelines rarely consider this route. METHODS: Systematic review of systematic reviews (PROSPERO CRD42018046504). We searched 6 databases published in English language from 1990 to June 2020, identifying subcutaneous infusions an alternate route for fluids or medication. Methodological quality was evaluated using AMSTAR 2 criteria and data for mechanisms of infusion and outcomes related to effectiveness, safety, efficiency and acceptability extracted. The Johanna Briggs Institute's grades of recommendation informed the strength of recommendation. RESULTS: The search yielded 1042 potential systematic reviews; 922 were excluded through abstract and duplicate screen. Of the remaining articles, 94 were excluded, and 26 were included. Overall, evidence is strong for recommending subcutaneous hydration infusions for older adults, weak for pediatric patients and inconclusive for palliative patients. There is strong evidence for 10 medications; weak evidence supporting 28 medications; however, there are eight medications with inconclusive evidence to make a recommendation and four medications not appropriate for subcutaneous delivery. CONCLUSION: Subcutaneous access should be considered alongside intravenous therapy for hydration in older adults, and several medications. There are additional benefits in terms of ease of use and cost-effectiveness of this mode. Inclusion of subcutaneous access in clinical guidelines may promote uptake of this route to help preserve vessel health of vulnerable patients. Further high-quality research is needed to inform subcutaneous infusion therapy in a variety of populations (including pediatrics and palliative care) and medications and clarifying the mechanism of delivery.

1,25(OH)2VitD3 supplementation enhances suppression of grass pollen-induced allergic asthma by subcutaneous and sublingual immunotherapy in a mouse model.

Allergen specific immunotherapy (AIT) can provide long-term alleviation of symptoms for allergic disease but is hampered by suboptimal efficiency. We and others have previously shown that 1,25(OH)2-VitaminD3 (VitD3) can improve therapeutic efficacy of AIT. However, it is unknown whether VitD3 supplementation has similar effects in sublingual and subcutaneous immunotherapy. Therefore, we aimed to test VitD3 supplementation in both grass pollen (GP) subcutaneous-IT (SCIT) and sublingual-IT (SLIT) in a mouse model for allergic airway inflammation. To this end, GP-sensitized BALB/c mice received GP-SCIT or GP-SLIT with or without 10 ng VitD3, followed by intranasal GP challenges and measurement of airway hyperresponsiveness (AHR) and inflammation. VitD3 supplementation of GP-SCIT resulted in enhanced induction of GP-specific (sp)-IgG2a and suppression of spIgE after challenge. In addition, eosinophil numbers were reduced and levels of IL10 and Amphiregulin were increased in lung tissue. In GP-SLIT, VitD3 supplementation resulted in enhanced sp-IgG2a levels in serum, enhanced suppression of eosinophils and increased IL10 levels in lung tissue, as well as suppression of AHR to methacholine. These data show that VitD3 increases efficacy of both SCIT and SLIT, by enhancing induction of blocking antibodies and suppression of airway inflammation, underscoring the relevance of proficient VitD3 levels for successful AIT.

Use of subcutaneous fluids in palliative care with children: a case study.

Quality of life is a major consideration in children's palliative care, particularly at the end of life. Optimal symptom management is crucial in maintaining quality of life, with the aim being to ensure the child is as comfortable as possible. Ensuring adequate hydration will often be part of symptom management but may be associated with several practical and ethical challenges. Subcutaneous fluid administration in children's palliative care is relatively uncommon, so there is a lack of evidence on the topic. This article demonstrates that it is feasible to use subcutaneous fluid therapy in the children's hospice setting to address patients' hydration needs and manage their symptoms. It presents a case study of a child who received subcutaneous fluids in a children's hospice for dehydration and myoclonus. It uses the case study to discuss subcutaneous fluid therapy in the children's palliative care setting, including its indications and contraindications, administration, complications and important factors to consider.

Hipodermóclise para correção de desidratação hiperosmolar e distúrbios eletrolíticos graves: relato de caso / Hypodermoclysis for correction of hyperosmolar dehydration and severe electrolyte disturbances: a case report

O tratamento de desidratação e distúrbios eletrolíticos graves é contraindicado por meio de hipodermóclise, mas o nível de evidência da recomendação se baseia na opinião de especialistas. Descreve-se caso clínico de paciente com idade avançada, com indicação de cuidados paliativos, que evoluiu com desidratação hiperosmolar com hipernatremia grave, injúria renal aguda e hipercalemia. Tratou-se a paciente com solução hipotônica por meio da técnica de hipodermóclise, com resolução completa do quadro. Conclui-se que há necessidade de mais estudos sobre o uso da hipodermóclise para o tratamento de distúrbios hidroeletrolíticos graves.

The treatment of dehydration and severe electrolyte disturbances using hypodermoclysis is usually contraindicated, but the level of evidence for its recommendation is based on expert opinion. This case report describes an older patient receiving palliative care who developed hyperosmolar dehydration with severe hypernatremia, acute kidney injury, and hyperkalemia. She was treated with hypodermoclysis using a hypotonic solution, which led to complete resolution of the condition. In conclusion, further studies on the use of hypodermoclysis for the treatment of severe hydroelectrolytic disorders are needed.

Effects of a pyroglutamyl pentapeptide isolated from fermented barley extract on atopic dermatitis-like skin lesions in hairless mouse.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic and eczematous skin lesions. The skin of AD patients is generally in a dried condition. Therefore, it is important for AD patients to manage skin moisturization. In this study, we examined the effects of orally administered fermented barley extract P (FBEP), which is prepared from a supernatant of barley shochu distillery by-product, on stratum corneum (SC) hydration and transepidermal water loss (TEWL) in AD-like lesions induced in hairless mice using 2,4,6-trinitrochlorobenzene. Oral administration of FBEP increased SC hydration and decreased TEWL in the dorsal skin of this mouse model. Further fractionation of FBEP showed that a pyroglutamyl pentapeptide, pEQPFP comprising all -L-form amino acids, is responsible for these activities. These results suggested that this pyroglutamyl pentapeptide may serve as a modality for the treatment of AD.

Hypodermoclysis as a Strategy for Patients With End-of-Life Cancer in Home Care Settings.

BACKGROUND: The increase in the elderly population associated with a higher incidence of cancer strongly endorses palliative care (PC). Hypodermoclysis (HDC) is a feasible technique for drugs and fluids delivery at the home care setting. OBJECTIVES: To assess the use and benefits of HDC in patients with end-of-life cancer assisted by a single home-based palliative care program (HPCP) in Belo Horizonte, Brazil. METHODS: This was a retrospective study that analyzed medical charts from patients with end-of-life cancer who were assisted by an HPCP in a 1-year period of time. RESULTS: A total of 333 patients, 81.7% with advanced cancer, were included. The most frequent symptoms were fatigue (44.4%) and pain (43.2%). Hypodermoclysis was used in 77.5% of the patients for the administration of fluids or medicines. Continuous palliative sedation was applied to 70.5% of patients. The place of death was home for 90.2% of the patients. CONCLUSION: Receiving home care assistance with palliative intention may decrease the need for dying patients with cancer to visit emergency units, as their symptoms were well controlled. Hypodermoclysis was a safe and effective alternative for hydration and drug delivery when provided and supervised by an experienced team. The place of death is a reliable indicator of the quality of death, and, in this study, the HPCP allowed patients to die at home with their families. It is essential for PC professionals to understand the impact of HDC use at home care setting for patients with end-of-life cancer allowing the increase of quality of death indicators.

Efficacy of Oral Nicorandil to Prevent Contrast-Induced Nephropathy in Patients with Chronic Renal Dysfunction Undergoing an Elective Coronary Procedure.

OBJECTIVES: This prospective, randomized study was to investigate the role of nicorandil in the prevention of contrast-induced nephropathy (CIN) in patients with chronic renal dysfunction undergoing an elective coronary procedure. METHODS: A total of 252 eligible patients were enrolled in this study and allocated into the control group (n = 125) or nicorandil group (n = 127). Both groups received the standard hydration treatment, and patients in the nicorandil group were orally administrated 10 mg of nicorandil (t.i.d.) beginning 2 days before and continuing for 2 days after an elective coronary procedure. Serum creatinine (SCr) and cystatin C (CysC) were measured at 24 h before and 24, 48, and 72 h after the procedure. The occurrences of CIN and adverse events within 1 year were recorded. RESULTS: The nicorandil group had relatively lower SCr and CysC levels and a higher eGFR at 24 and 48 h after the procedure than the control group (p < 0.05). The incidence of CIN was significantly decreased in the nicorandil group compared to the control group. The multivariate logistic regression model revealed that nicorandil treatment was an independent protective factor for CIN (OR 0.669, 95% CI 0.522-0.857, p = 0.001). The multivariate COX proportional hazard model showed that nicorandil treatment was an independent protective predictor for adverse events (HR 0.881, 95% CI 0.781-0.993, p = 0.037). CONCLUSIONS: Nicorandil could exhibit a protective effect against CIN in patients with chronic renal dysfunction undergoing an elective coronary procedure and reduce the adverse events within 1 year after the procedure, which is superior to hydration treatment only.

Availability and perceived usefulness of guidelines and protocols for subcutaneous hydration in palliative care settings.

AIMS AND OBJECTIVES: To evaluate the availability of, adherence to, and perceived usefulness of guidelines and protocols for managing hydration and subcutaneous hydration in palliative care settings. BACKGROUND: Hydration at the end of life and the use of a subcutaneous route to hydrate generate some controversy among health professionals for different reasons. Having guidelines and protocols to assist in decision-making and to follow a standard procedure may be relevant in clinical practice. DESIGN: Cross-sectional telephone survey, with closed-ended and open-ended questions designed specifically for this study. METHODS: Data were obtained from 327 professionals, each from a different palliative care service. Mean, standard deviation, minimum and maximum were calculated for continuous variables; frequency distributions were obtained for categorical variables. A qualitative content analysis was performed on the open-ended questions. The article adheres to the STROBE guidelines for reporting observational studies. RESULTS: Only 24.8% of the participants had guidelines available to assist in making decisions regarding hydration, and 55.6% claimed to follow them 'always or almost always'. Of the participants, 38.8% had subcutaneous hydration protocols available, while 78.7% stated that they 'always or almost always' followed these protocols. The remaining participants considered the protocols as useful tools despite not having them available. CONCLUSIONS: Only 25% of the participants' services had guidelines for hydration, and less than 40% had protocols for subcutaneous hydration. However, adherence was high, especially in cases where protocols existed. Among the participants who did not have guidelines and protocols, attitudes were mostly favourable, but mainly as a reference and support for an individualised clinical practice. RELEVANCE TO CLINICAL PRACTICE: Guidelines and protocols on hydration in palliative care may be more useful as a solid reference and support for individualised practice than as instruments for standardising care. From this perspective, their development and availability in palliative care services are recommended.

Influence of Peripheral Neuropathy and Microangiopathy on Skin Hydration in the Feet of Patients With Diabetes Mellitus.

INTRODUCTION: Maintaining adequate skin hydration is crucial in the feet of patients with diabetes because xerotic skin may crack and develop fissures, thereby increasing vulnerability to ulceration and infection. The nervous system is considered the powerhouse for maintaining adequate skin hydration; however, no clinical study has assessed the effect of the nervous system on skin hydration. In addition, it is hypothesized that microcirculation may play an important role in maintaining adequate hydration in patients with diabetes. OBJECTIVE: This study aims to evaluate the influence of peripheral nerve function and microvascularity on skin hydration in the feet of patients with diabetes mellitus and compare the effects of these 2 functions on skin hydration. MATERIALS AND METHODS: This study included 266 patients with diabetic foot disease. Skin hydration was evaluated using corneometry and microvascularity by measuring the transcutaneous oximetry (TcpO2) of the foot. The Semmes-Weinstein 5.07/10-g monofilament test, electromyography, and nerve conduction velocity test were conducted to evaluate peripheral neuropathy. Patient data were divided into 3 subgroups according to test values, and statistical comparisons were performed using the linear-by-linear association trend and Pearson's chi-square tests. RESULTS: There was a significant correlation between skin hydration and TcpO2. However, there was no significant correlation between skin hydration and peripheral nerve function (P = .338). CONCLUSIONS: The results of this study demonstrated that skin hydration in the feet of patients with diabetes mellitus mainly is influenced by microcirculation rather than peripheral nerve function.

Vasopressor support vs. liberal fluid administration in deep inferior epigastric perforator (DIEP) free flap breast reconstruction - a randomized controlled trial.

BACKGROUND: Perioperatively, patients' hemodynamics are modulated predominantly by intravenous fluid administration and vasoactive pharmacological support. Vasopressor agents are suspected to be detrimental on free flap survival by the cause of vasoconstriction of the pedicle with consecutive reduced overall flap perfusion and by aggravation of flap dissection. OBJECTIVE: A novel, standardized fluid restrictive perioperative hemodynamic management was assessed for its feasibility in clinical practice in free flap patients undergoing breast reconstruction. METHODS: Patients were randomized to two perioperative regimens with different fluid and vasopressor limits. The primary endpoint regarded flap survival. Secondary endpoints included surgery times, time of patient ambulation and length of hospital stay. RESULTS: There was one total flap failure with liberal fluid administration (LFA). No total or partial flap failure was noted in the fluid restrictive regimen with norepinephrine administration up to 0.04µg/kg/min (FRV). No delay regarding operation time (p = 0.217), patient mobilization (p = 0.550) or hospital discharge (p = 0.662) was registered in the FRV study subpopulation compared to LFA. CONCLUSIONS: The results of this prospective interventional trial could not detect any negative impact of vasopressors, neither for the primary endpoint of flap survival nor for the overall patient outcome. The fear of vasopressor associated flap complications has led to a traditional liberal fluid administration, which failed to demonstrate any benefits when compared to a fluid restrictive vasopressor strategy.

Characterization of Water Self-Diffusion in Human Stratum Corneum.

The stratum corneum (SC) is the outermost layer of human skin and primary barrier to water loss and chemical exposure. It consists of keratin-filled corneocytes of large aspect ratio surrounded by a thin matrix of highly organized lipophilic molecules. In the presence of water, the corneocytes swell and permeability for many chemicals increases. The role of hydration and SC structure on water self-diffusion was investigated using the pulsed-gradient stimulated echo nuclear magnetic resonance technique. Proton (1H) self-diffusion, associated with water inside the corneocytes, was determined in human SC as a function of hydration, with and without lipid extraction, at 20°C to 40°C. SC layers were oriented either parallel or perpendicular to the field-gradient direction. Self-diffusion in the direction parallel to the long dimension of the corneocytes is unaffected by lipid extraction and consistent with a free-volume diffusion model. The effect of temperature corresponds with the activation energy of water in wool. Self-diffusion perpendicular to the long dimension of the corneocytes was less dependent on hydration and smaller than in the parallel direction, except at low hydration, when diffusion is insensitive to orientation. Corneocyte diffusion predicted by 2 microscopic SC models in common use are compared with our results.

N-Acetylglutaminoyl-S-farnesyl-L-cysteine (SIG-1191): an anti-inflammatory molecule that increases the expression of the aquaglyceroporin, aquaporin-3, in human keratinocytes.

Isoprenylcysteine (IPC) small molecules were discovered as signal transduction modulating compounds ~25 years ago. More recently, IPC molecules have demonstrated antioxidant and anti-inflammatory properties in a variety of dermal cells as well as antimicrobial activity, representing a novel class of compounds to ameliorate skin conditions and disease. Here, we demonstrate a new IPC compound, N-acetylglutaminoyl-S-farnesyl-L-cysteine (SIG-1191), which inhibits UVB-induced inflammation blocking pro-inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) production. To investigate further the previously reported hydrating potential of IPC compounds, SIG-1191 was tested for its ability to modulate aquaporin expression. Specifically, aquaporin 3 (AQP3) the most abundant aquaporin found in skin has been reported to play a key role in skin hydration, elasticity and barrier repair. Results show here for the first time that SIG-1191 increases AQP3 expression in both cultured normal human epidermal keratinocytes as well as when applied topically in a three-dimensional (3D) reconstructed human skin equivalent. Additionally, SIG-1191 dose dependently increased AQP3 protein levels, as determined by specific antibody staining, in the epidermis of the 3D skin equivalents. To begin to elucidate which signaling pathways SIG-1191 may be modulating to increase AQP3 levels, we used several pharmacological pathway inhibitors and determined that AQP3 expression is mediated by the Mitogen-activated protein kinase/Extracellular signal-regulated kinase kinase (MEK) pathway. Altogether, these data suggest SIG-1191 represents a new IPC derivative with anti-inflammatory activity that may also promote increased skin hydration based on its ability to increase AQP3 levels.

Primary hyperparathyroidism in pregnancy treated with cinacalcet: a case report and review of the literature.

BACKGROUND: The efficacy and safety of various modes of medical treatment for primary hyperparathyroidism in pregnancy are largely unknown. CASE PRESENTATION: We report the case of a 34-year-old white woman with primary hyperparathyroidism symptomatic for nephrolithiasis. Her serum calcium was 3.15 mmol/l and parathyroid hormone was 109.0 ng/L. Neck imaging found no pathological parathyroid tissue. Cinacalcet and cholecalciferol were started. She became pregnant 17 months later. The calcimimetic was stopped. During pregnancy, she was admitted for hydration administered intravenously two to three times per week. In her 24th week of pregnancy, cinacalcet was restarted. In her 32nd week, a cesarean section was carried out as planned. CONCLUSIONS: Only three cases of primary hyperparathyroidism in women on cinacalcet therapy in pregnancy have been published in the literature. In the present case, hydration was useful in controlling serum calcium. Cinacalcet therapy helped to control serum calcium.

Systematic review: periprocedural hydration in the prevention of post-ERCP pancreatitis.

BACKGROUND: With an overall incidence of 3.5%, pancreatitis is the most frequent complication of endoscopic retrograde cholangiopancreatography (ERCP). Periprocedural hydration may prevent post-ERCP pancreatitis by maintaining pancreatic microperfusion, thereby inhibiting the pancreatic inflammatory response. However, the evidence for periprocedural hydration as a preventive measure is unclear. AIM: To conduct a systematic review to assess the evidence regarding periprocedural hydration as a preventive measure for post-ERCP pancreatitis. METHODS: We searched PubMed and EMBASE databases and adhered to the PRISMA guidelines. We included studies addressing periprocedural hydration as a preventive measure to reduce frequency and severity of post-ERCP pancreatitis. Study quality was assessed by using the MINORS and Cochrane Collaboration's tool. RESULTS: Six studies with a total of 1102 patients were included. Two randomised controlled trials reported a decreased incidence of post-ERCP pancreatitis after hydration: 0% vs. 17% (P = 0.016) and 5.3% vs. 22.7% (P = 0.002). A third trial and two case-controls studies did not report significant differences. Two retrospective studies found that patients with mild post-ERCP pancreatitis had received significantly more fluids during (mean 940 mL vs. 810 mL; P = 0.031) or after ERCP (median 2834 mL vs. 2044 mL; P < 0.02) compared to patients with moderate/severe disease. Adverse events of periprocedural hydration were not reported in any of the included studies. The different methodologies of the included studies precluded a formal data synthesis. CONCLUSIONS: There is some evidence to suggest that hydration affords protection against post-ERCP pancreatitis, but study heterogeneity precludes firm conclusions. Adequately powered randomised trials are needed to evaluate the preventive effect of periprocedural hydration.

Manejo de la vía subcutánea en cuidados paliativos / Management of the subcutaneous way of administration in paliative care

El envejecimiento de la población, el aumento de enfermedades crónico-degenerativas, junto con una mayor esperanza de vida hacen que cada día el número de pacientes que requieren cuidados paliativos sea mayor. La vía de elección para tratar los síntomas en estos pacientes es la oral, pero ciertas circunstancias pueden imposibilitar su uso, siendo necesario recurrir a otras vías. La vía subcutánea supone una alternativa en estas situaciones al tratarse de una técnica sencilla, segura y de fácil manejo. El propósito de este trabajo es contribuir al buen uso de esta técnica y, por lo tanto, a un mejor control de los síntomas, describiendo la técnica, las ventajas y desventajas de su uso en cuidados paliativos, indicaciones y contraindicaciones, las posibles complicaciones, lugares y técnica de inserción, los cuidados posteriores, así como los tipos de administración y fármacos más empleados

The population ageing, the increase of chronic-degenerative diseases, together with a higher life expectancy, have led to an increasing number of patients who require palliative care. The administration way of choice to treat symptoms in these patients will be oral, but certain circumstances may render this impossible, making it necessary to resort to other ways. The subcutaneous way represents an alternative option in these situations, as it is a simple, safe, and easy to use technique. The objective of this paper is to contribute towards the good use of this technique and, therefore, to a better control of symptoms, describing the techniques, the advantages and disadvantages of its use in Palliative Care, indications and contraindications, potential complications, insertion sites and technique, subsequent care, as well as the most widely used types of administration and drugs

Dehydration, Hypernatremia, and Hyponatremia.

Disturbances of serum sodium are one of the most common findings in older persons. They are also a major cause of hospital admissions and delirium and are associated with frailty, falls, and hip fractures. Both hypernatremia and hyponatremia are potentially preventable. Treatment involves treating the underlying cause and restoring sodium and volume status to normal. The arginine vasopressin antagonists, vaptans, have increased the therapeutic armamentarium available to physicians.

[Subcutaneous rehydration for efficient treatment of elderly people during heat-waves]. / Subkutane Flüssigkeitssubstitution bei betagten Patienten während Hitzewellen.

Geriatric patients were more often treated in hospitals for Dehydration in the last years resembling a rising burden for Health systems. Elderly people are more vulnerable for Dehydration during Heat Waves especially when there are complicating factors like febrile episodes or multiple medications. In private care situations as in homes for elderly Strategies have to be implemented in Germany to prevent hospital admissions in the case of transient Dehydration. By this a rise of costs and a waste of resources should be diminished. Prehospital structures have to be implemented to maintain oral Rehydration aware of a more intensive care. At the same time there is the need to use the parenteral method of subcutaneous infusion (Hypodermoclysis) for a defined time.

Hypodermoclysis: a literature review to assist in clinical practice.

The aim of this study was to analyze the information available in the literature about the drugs that can be administered through hypodermoclysis and the resulting impact that this information may have on the routine of the pharmacist working at a hospital. The study was based on a review of the literature. The results showed positive points of the procedure, but little specific information about medications such as routes of administration, standard dilutions, optimal doses, etc. Thus, it was possible to verify that there is no definite information as to the correct way to administer the drugs in this route, even though this is an effective and safe option, according to the literature. The lack of information has a negative impact on the support provided by the pharmacist to the nursing staff to ensure that the drug actually reaches its therapeutic goals safely.

Hypodermoclysis: a literature review to assist in clinical practice / Hipodermóclise: revisão de literatura para auxiliar a prática clínica

The aim of this study was to analyze the information available in the literature about the drugs that can be administered through hypodermoclysis and the resulting impact that this information may have on the routine of the pharmacist working at a hospital. The study was based on a review of the literature. The results showed positive points of the procedure, but little specific information about medications such as routes of administration, standard dilutions, optimal doses, etc. Thus, it was possible to verify that there is no definite information as to the correct way to administer the drugs in this route, even though this is an effective and safe option, according to the literature. The lack of information has a negative impact on the support provided by the pharmacist to the nursing staff to ensure that the drug actually reaches its therapeutic goals safely.

O objetivo desse trabalho, foi analisar, na literatura, as informações disponíveis sobre os medicamentos que podem ser administrados através da hipodermóclise e o impacto que a informação pode acarretar na rotina do farmacêutico dentro de uma unidade hospitalar. O estudo foi baseado em uma revisão de literatura. Os resultados encontrados, demonstraram pontos positivos do procedimento, porém foram localizadas poucas informações específicas sobre medicamentos, como métodos de administração, padrões de diluição, dose ideal etc. Dessa forma, foi possível verificar que não há informações definitivas quanto ao modo mais correto de se administrar as drogas por essa via, mesmo sendo esta uma opção eficaz e segura, conforme a literatura. A falta de informação impacta negativamente no suporte realizado pelo farmacêutico à equipe de enfermagem para garantir que o medicamento realmente alcance seus objetivos terapêuticos com segurança.

Hydrogel-based ultra-moisturizing cream formulation for skin hydration and enhanced dermal drug delivery.

To develop an external vehicle for skin hydration and enhanced dermal drug delivery, a hydrogel-based ultra-moisturizing cream (HUMC) was successfully formulated with carbopol 934P, urea, Tinocare GL, grape seed oil, and other excipients. The HUMC showed plastic flow behavior due to a gel structure with a cream base. Different types of drug-free vehicles such as a hydrogel, conventional cream (CC), and three HUMCs were prepared and subjected to an in vivo skin hydration test on a hairless mouse using a corneometer. Hydration effect (∆AU) was in the order of HUMC2>HUMC1 ≥ CC>HUMC3>hydrogel. Using nile red (NR) and 5-carboxyfluorescein (5-CF) as lipophilic and hydrophilic fluorescent probes, respectively, in vitro skin permeation and accumulation studies were conducted using Franz diffusion cells. The values of steady-state flux (Jss, ng/h/cm(2)) were obtained: 74.8 (CC), 145.6 (HUMC1), and 161.9 (HUMC2) for NR delivery; 6.8 (CC), 8.3 (HUMC1), and 10.9 (HUMC2) for 5-CF delivery. The amounts retained in the skin at 12 h (Qr, ng/cm(2)) were determined: 86.4 (CC) and 102.0 (HUMC2) for NR; and 70.1 (CC) and 195.6 (HUMC2) for 5-CF. Confocal microscopy was used to visualize the distribution of the fluorescent probes. NR tended to be localized into the deeper part of the skin with adipose tissue whereas 5-CF localized in the upper layer of the skin. Thus we propose that HUMC2 is an efficacious vehicle for skin hydration and enhances dermal delivery of lipophilic and hydrophilic drugs.