Systemic Availability Of Drug Research Articles

Mesoporous Silica-Based Membranes in Transdermal Drug Delivery: The Role of Drug Loss in the Skin.

Compared to other forms of drug administration, the use of Transdermal Drug Delivery Systems (TDDSs) offers significant advantages, including uniform drug release profiles that contribute to lower side effects and higher tolerability, avoidance of direct exposure to the gastrointestinal tract, better patient compliance due to their non-invasive means of application and others. Mesoporous silica membranes are of particular interest in this regard, due to their chemical stability and their tunable porous system, with adjustable pore sizes, pore volumes and surface chemistries. While this allows for fine-tuning and, thus, the development of optimized TDDSs with high loading capacities and the desired release profile of a given drug, its systemic availability also relies on skin penetration. In this paper, using a TDDS based on mesoporous silica membranes in Franz cell experiments on porcine skin, we demonstrate surprisingly substantial drug loss during skin penetration. Drug passage through porcine skin was found to be dependent on the age and pre-treatment of the skin. pH and temperature were major determinants of drug recovery rates as well, indicating drug loss in the skin by enzymatic metabolization. Regarding the TDDS, higher loading obtained by SO3H surface modification of the mesoporous silica membranes reduced drug loss. Still, high loss rates in the skin were determined for different drugs, including anastrozole, xylazine and imiquimod. We conclude that, beyond the fine-tuned drug release profiles from the mesoporous silica membrane TDDS, remarkably high drug loss in the skin is a major issue for achieving desired skin penetration and, thus, the systemic availability of drugs. This also poses critical requirements for defining an optimal TDDS based on mesoporous silica membranes.

Preclinical pharmacokinetics, pharmacodynamics, and toxicity of novel small-molecule GPR119 agonists to treat type-2 diabetes and obesity

The escalating global prevalence of type-2 diabetes (T2D) and obesity necessitates the development of novel oral medications. Agonism at G-protein coupled receptor-119 (GPR119) has been recognized for modulation of metabolic homeostasis in T2D, obesity, and fatty liver disease. However, off-target effects have impeded the advancement of synthetic GPR119 agonist drug candidates. Non-systemic, gut-restricted GPR119 agonism is suggested as an alternative strategy that may locally stimulate intestinal enteroendocrine cells (EEC) for incretin secretion, without the need for systemic drug availability, consequently alleviating conventional class-related side effects. Herein, we report the preclinical acute safety, efficacy, and pharmacokinetics (PK) of novel GPR119 agonist compounds ps297 and ps318 that potentially target gut EEC for incretin secretion. In a proof-of-efficacy study, both compounds demonstrated glucagon-like peptide-1 (GLP-1) secretion capability during glucose and mixed-meal tolerance tests in healthy mice. Furthermore, co-administration of sitagliptin with investigational compounds in diabetic db/db mice resulted in synergism, with GLP-1 concentrations rising by three-fold. Both ps297 and ps318 exhibited low gut permeability assessed in the in-vitro Caco-2 cell model. A single oral dose PK study conducted on healthy mice demonstrated poor systemic bioavailability of both agents. PK measures (mean ± SD) for compound ps297 (Cmax 23 ± 19 ng/mL, Tmax range 0.5 – 1 h, AUC0–24 h 19.6 ± 21 h*ng/mL) and ps318 (Cmax 75 ± 22 ng/mL, Tmax range 0.25 – 0.5 h, AUC0–24 h 35 ± 23 h*ng/mL) suggest poor oral absorption. Additionally, examinations of drug excretion patterns in mice revealed that around 25 % (ps297) and 4 % (ps318) of the drugs were excreted through faeces as an unchanged form, while negligible drug concentrations (<0.005 %) were excreted in the urine. These acute PK/PD assessments suggest the gut is a primary site of action for both agents. Toxicity assessments conducted in the zebrafish and healthy mice models confirmed the safety and tolerability of both compounds. Future chronic in-vivo studies in relevant disease models will be essential to confirm the long-term safety and efficacy of these novel compounds.

A qualitative study on determinants of the use of malaria rapid diagnostic test and anti-malarial drug prescription practices by primary healthcare workers in Ebonyi state, Nigeria

BackgroundThe increased availability and use of malaria rapid diagnostic test (RDT) by primary healthcare (PHC) workers has made universal diagnostic testing before malaria treatment more feasible. However, to meaningfully resolve the problem of over-treatment with artemisinin-based combination therapy and the heightened risk of selection pressure and drug resistance, there should be appropriate response (non-prescription of anti-malarial drugs) following a negative RDT result by PHC workers. This study explored the determinants of the use of RDT and anti-malarial drug prescription practices by PHC workers in Ebonyi state, Nigeria.MethodsBetween March 2 and 10, 2020, three focus group discussions were conducted in English with 23 purposively-selected consenting PHC workers involved in the diagnosis and treatment of malaria. Data was analysed thematically as informed by the method by Braun and Clarke.ResultsThe determinants of the use of RDT for malaria diagnosis were systemic (RDT availability and patient load), provider related (confidence in RDT and the desire to make correct diagnosis, PHC worker’s knowledge and training, and fear to prick a patient), client related (fear of needle prick and refusal to receive RDT, and self-diagnosis of malaria, based on symptoms, and insistence on not receiving RDT), and RDT-related (the ease of conducting and interpreting RDT). The determinants of anti-malarial drug prescription practices were systemic (drug availability and cost) and drug related (effectiveness and side-effects of the drugs). The determinants of the prescription of anti-malarial drugs following negative RDT were provider related (the desire to make more money and limited confidence in RDT) and clients’ demand while unnecessary co-prescription of antibiotics with anti-malarial drugs following positive RDT was determined by the desire to make more money.ConclusionsThis evidence highlights many systemic, provider, client, and RDT/drug related determinants of PHC workers’ use of RDT and anti-malarial drug prescription practices that should provide tailored guidance for relevant health policy actions in Ebonyi state, Nigeria, and similar settings.

Formulation Development and Evaluation of Fast Dissolving Oral Film of Midodrine Hydrochloride

Oral fast dissolving midodrine hydrochloride films prepared by solvent casting method, PEG 400 was the selected plasticizers, incorporating superdisintegrants such as croscarmellose sodium (CCS) and sodium starch glycolate (SSG) to achieve the goal. Drug content, weight variability, film thickness, disintegration time, endurance, percentage of moisture content, and in vitro dissolution tests were analyzed for the prepared films. In all formulations, the tensile strength value was found from 0.965±0.045 and 1.256±0.032 and the folding capacity was over 100. The assay values ranged from 97.98±0.25 to 99.89±0.36 percent for all formulations. The disintegration time was ranging between 55±9 to 120±6 sec, the minimum time for disintegration was found in formulation F5 (55±9). The prepared F5 formulation shows greater release of the drug (99.25±0.41 percent) within 15 min relative to other formulations. As the drug having low solubility, fast disintegration may leads to more drug availability for dissolution, resulting in faster absorption in systemic circulation increased systemic availability of drug leads to quick onset of action which is prerequisite for hypertension.&#x0D; Keywords: Midodrine hydrochloride, Fast dissolving films, Solvent casting method, Superdisintegrants.

AN OVERVIEW ON INTRANASAL DRUG DELIVERY SYSTEM: RECENT TECHNIQUE AND ITS CONTRIBUTION IN THERAPEUTIC MANAGEMENT

Nasal drug administration has been used as an important another route for the systemic availability of drugs. Intranasal route has large surface area, high total blood flow, avoidance of first-pass metabolism, porous endothelial membrane, and ready accessibility. For nasal route administration various drugs including peptide and protein drugs, for systemic medication has been widely used in recent few years. This review article highlights the importance, strategies and advantages of the nasal drug delivery systems. Various methods are discussed here for increasing the residence time of drug formulations in the nasal cavity, for improving nasal drug absorption. In this review article we discuss the effects of bioadhesive drug delivery systems on nasal drug administration. Drug delivery systems (such as nanoemulsion, microspheres, liposome and gels) have good bioadhesive characteristics which swell easily when in contact with the nasal mucosa. These types of drug delivery systems protect the drug from enzymatic degradation in nasal secretions and also control the rate of drug clearance from the nasal cavity.

Formulation and Evaluation of an Injectable Dosage Form

The various initial formulations of the developed and those are examined for drug release profile, bioavailability, and clinical effectiveness and for the pilot plant studies and production scale-up. The drug that we need should be most convenient and in proper form then only it reaches to the desired site of action. This is greatly influenced by which the type of dosage form of the drug. Since, injections include much variety of therapeutic agents. Injections are sterile, pyrogen limited, that is, bacterial endotoxin units limit, preparations intended to be administered parenterally. It is well recognized that the advantages of parenteral injections are immediate systemic drug availability and rapid onset of action.

Lymphatic Drug Absorption via the Enterocytes: Pharmacokinetic Simulation, Modeling, and Considerations for Optimal Drug Development.

Most orally administered drugs gain access to the systemic circulation by direct passage from the enterocyte layer of the intestinal tract to the mesenteric blood capillaries. Intestinal lymphatic absorption is another pathway that certain drugs may follow to gain access to the systemic circulation after oral administration. Once absorbed, drug diffuses into the intestinal enterocyte and while in transit may associate with fats as they are processed into chylomicrons within the cells. The chylomicron-associated drug is then secreted from the enterocyte into the lymphatic circulation, thus avoiding the hepatic first-pass liver metabolism, and ultimately entering to the systemic circulation for disposition and action. Due to the possibility of parallel and potentially alternative absorptive pathways, mesenteric blood capillary and lymphatic drug exposure are both potential pathways of systemic availability for any individual drug. In this report, an in silico modeling approach was adopted to delineate the salient pharmacokinetic features of lymphatic absorption, and provide further guidance for the rationale design of drugs and drug delivery systems for lymphatic drug transport. The importance of hepatic extraction ratio, absorption lag time, lipoprotein binding, and the influence of competing portal and lymphatic pathways for systemic drug availability were explored using simulations. The degree of hepatic extraction was found to be an essential consideration when examining the influence of lymphatic uptake to overall oral drug bioavailability. Lymphatic absorption could potentially contribute to multiple peaking phenomena and flip flop pharmacokinetics of orally administered drugs.

FORMULATION AND EVALUATION OF AN INJECTABLE SOLUTION AS A DOSAGE FORM

The present study will outline formulation and the evaluation methods of injectable dosage form. The various initial formulations of the developed and those are examined for drug release profile, bioavailability, and clinical effectiveness and for the pilot plant studies and production scale-up. The drug that we need should be most convenient and in proper form then only it reaches to the desired site of action. This is greatly influenced by which the type of dosage form of the drug. Since, injections include much variety of therapeutic agents. Injections are sterile, pyrogen limited, that is, bacterial endotoxin units limit, preparations intended to be administered parenterally. It is well recognized that the advantages of parenteral injections are immediate systemic drug availability and rapid onset of action.&#x0D; Keywords: Injectable, Parenteral, Sterilization, Tonicity

Relative Oral Bioequivalence of Two 6-Mercaptopurine (6-MP) Liquid Formulations in Children with Acute Lymphoblastic Leukemia (ALL)

Introduction: Oral 6-MP remains a key drug for acute and maintenance treatment of ALL. Maintaining adequate systemic exposure so as to prevent disease relapse is challenging given variability in the pharmacokinetics (PK). Historically, pharmacies have prepared extemporaneous formulations of 6-MP to permit more individualized (i.e. mg/kg) and accurate dosing in small children which is difficult when using fixed dose tablets. We performed a preliminary investigation of the relative bioequivalence (rBE) of two extemporaneous oral liquid formulations of 6-MP.Methods: Children with ALL participated in a randomized, 2-sequence, 2-period crossover study conducted at a single site. In study arm A, patients received a 5 mg/ml oral, liquid formulation of 6-MP prepared in 1:1 Ora-Plus®:Ora-Sweet and a marketed 50 mg tablet (Roxane Laboratories). Study arm B evaluated a 50 mg/ml liquid formulation prepared in methylcellulose and simple syrup against the 50 mg tablet. Participants were administered their prescribed 6-MP dose following an overnight fast. Serial blood samples (n=14) were collected prior to and over 8 hours post-dose. Plasma 6-MP concentrations were quantitated under GLP conditions using a validated, LC-MS/MS method. 6-MP PK was determined using a standard noncompartmental approach. The relative oral bioavailability of 6-MP was determined by generating 90% confidence intervals for log transformed ratios (test/reference) of Cmax, AUC0-n, and AUC0-inf.Results: Twenty four participants (6-17 yrs) enrolled in this study. Eleven subjects (6 female) were in the 5 mg/ml study arm and 13 (8 female) were in the 50 mg/ml study arm.The inverse log of the 90% confidence interval generated by the ratio of thedifferences in exposures between the respective oral liquid formulations versus the tablet were as follows:Table 1ParameterTest Formulations5 mg/ml liquid50 mg/ml liquidCmax (ng/ml)1.64-2.721.07-1.72AUC0-n (ng/ml*hr)1.10-1.650.85-1.17AUC0-inf (ng/ml*hr)1.10-1.650.84-1.13All estimates of exposure for the 5 mg/ml liquid exceeded the accepted range of bioequivalence (i.e. 0.80-1.25) per FDA criteria. Cmax for the 50 mg/ml liquid similarly exceeded theaccepted range. In contrast, AUC0-n and AUC0-inf for this particular formulation were within the accepted range based on FDA criteria.Conclusions: While both liquid formulations exhibited comparable bioavailability, neither formulation was bioequivalent to the tablet formulation for both Cmax and AUC. The systemic exposure to 6-MP (as reflected by AUC) from the 50 mg/ml oral liquid was bioequivalent to the tablet. Our data demonstrate that not all liquid formulations of 6-MP are equivalent with respect to bioavailability of the active ingredient. Differences in formulation constituents (e.g., suspending agents, vehicles), viscosity and potentially, 6-MP concentration likely contribute to the variability observed in systemic drug availability from liquid formulations and must be considered. DisclosuresNo relevant conflicts of interest to declare.

Aerosolized semifluorinated alkanes as excipients are suitable for inhalative drug delivery—A pilot study

Semifluorinated alkanes (SFAs) have been described as potential excipients for pulmonary drug delivery, but proof of their efficacy is still lacking. We tested whether SFA formulations with the test drug ibuprofen can be nebulised and evaluated their pharmacokinetics. Physico-chemical properties of five different ibuprofen formulations were evaluated: an aqueous solution (H2O), two different SFAs (perfluorohexyloctane (F6H8), perfluorobutylpentane (F4H5)) with and without ethanol (SFA/EtOH). Nebulisation was performed with a jet catheter system. Inhalative characteristics were evaluated by laser diffraction. A confirmative animal study with an inhalative single-dose (6 mg/kg) of ibuprofen with each formulation was performed in anaesthetised healthy rabbits. Plasma samples at defined time points and lung tissue harvested after the 6-h study period were analyzed by HPLC–MS/MS. Pharmacokinetics were calculated using a non-compartment model. All formulations were nebulisable. No differences in aerodynamic diameters (MMAD) were detected between SFA and SFA/EtOH. The ibuprofen plasma concentration–time curve (AUC) was highest with F4H5/EtOH. In contrast, F6H8/EtOH had the highest deposition of ibuprofen into lung tissue but the lowest AUC. All tested SFA and SFA/EtOH formulations are suitable for inhalation. F4H5/EtOH formulations might be used for rapid systemic availability of drugs. F6H8/EtOH showed intrapulmonary deposition of the test drug.

Countering Drug Resistance in the Developing World: An Assessment of Incentives Across the Value Chain and Recommendations for Policy Intervention

The emergence and spread of drug resistance is draining available resources and threatening our ability to treat infectious diseases in developing countries. HIV/AIDS, tuberculosis, malaria, diarrhea, and respiratory tract infections continue to be the leading causes of death in many developing countries, many of which have already been exacerbated by resistance. Countering drug resistance often involves complex tradeoffs between activities such as the development of new products; ensuring treatment heterogeneity; and guaranteeing quality and ensuring systemic availability, affordability, compliance, adherence and rational use of drugs and diagnostics. A careful understanding of all the players involved in the resistance problem and their incentives to engage in activities that counter drug resistance is crucial for policymakers and resource managers in a range of institutions and agencies. This paper presents results gathered through quasi-structured interviews to understand these incentives and develop recommendations to better align them with resistance-countering activities.

Cardiac arrest in intensive care unit: Case report and future recommendations

Initiation of hemofiltration in a patient in septic shock can cause hemodynamic compromise potentially leading to cardiac arrest. We propose that the standard '4Hs and 4Ts' approach to the differential diagnosis of a cardiac arrest should be supplemented in critically ill patients with anaphylaxis and human and technical errors involving drug administration (the 5th H and T). To illustrate the point, we report a case where norepinephrine infused through a central venous catheter (CVC) was being removed by the central venovenous hemofiltration (CVVH) catheter causing the hemodynamic instability. CVVH has this potential of interfering with the systemic availability of drugs infused via a closely located CVC.

Effects of Aging on the Human Taste System

Losses in taste perception as well as distortions of gustatory function occur with greater frequency in older individuals, and these changes are exacerbated by certain medical conditions, pharmacologic interventions, radiation, and exposure to toxic chemicals. Medications, especially drug-drug interactions, are the most significant yet underappreciated contributors to taste disorders in the elderly. Taste disorders frequently occur when the fraction of an orally administered drug dose that reaches the systemic circulation is markedly increased due to inhibition (by a coadministered drug) of the efflux transporter P-glycoprotein and/or inhibition of the cytochrome P450 metabolism system, which normally limit systemic availability of drugs. The supratherapeutic plasma drug concentrations that result from drug-drug interactions can induce a taste from the blood side of taste cells (intravascular taste), alter taste cell biochemistry, and/or modify other aspects of the taste pathways.

Involvement of P‐glycoprotein on ivermectin kinetic behaviour in sheep: itraconazole‐mediated changes on gastrointestinal disposition

Different pharmacological approaches have been used in an attempt to increase the systemic availability of anthelmintic drugs. The comparative effect of the itraconazole (ITZ)-mediated modulation of P-glycoprotein (P-gp) activity on the in vivo kinetic behaviour of ivermectin (IVM) administered by the intravenous (i.v.) and intraruminal (i.r.) routes to sheep was assessed in the current work. Corriedale sheep received IVM (50 microg/kg) by the i.v. route either alone (group A) or co-administered with the P-gp modulator ITZ (100 mg orally three times every 12 h) (group B). Animals in groups C and D were intraruminally treated with IVM (50 microg/kg) alone or co-administered with ITZ (100 mg orally three times every 12 h) respectively. Jugular blood and gastrointestinal tissue samples (animals treated by the i.r. route) were collected. The samples were analysed by HPLC using fluorescence detection. The plasma disposition of IVM given intravenously was unaffected by the presence of ITZ. However, after the i.r. treatment the co-administration with ITZ resulted in markedly higher IVM plasma concentration profiles compared to the control group. Likewise, the presence of ITZ enhanced the IVM concentration profiles measured in the gastrointestinal mucosal tissues. An ITZ-induced reduction on the P-gp efflux activity at the intestinal lining may have accounted for the greater absorption and enhanced systemic availability observed for IVM in the intraruminally treated animals.

Nasal Drug Delivery System-Factors Affecting and Applications

The nasal route is a potential alternative route for systemic availability of drugs restricted to intravenous administration, such as peptide and protein drugs and vaccines. This route is also advisable for drugs undergoing extensive first pass effect .Besides this, intranasal route has also been successfully exploited for bypassing the blood brain barrier [BBB] and subsequently delivering drug molecules to central nervous system [CNS]. The present article highlights the advantages, barriers, physicochemical factors and formulation related parameters affecting the nasal drug delivery. It also includes a note on nasal absorption enhancers. Also, the applications of nasal route for delivery of peptides and proteins, non-peptide drugs, vaccines and drug molecules to CNS have been summarized in depth.

Nasal route and drug delivery systems.

Nasal drug administration has been used as an alternative route for the systemic availability of drugs restricted to intravenous administration. This is due to the large surface area, porous endothelial membrane, high total blood flow, the avoidance of first-pass metabolism, and ready accessibility. The nasal administration of drugs, including numerous compound, peptide and protein drugs, for systemic medication has been widely investigated in recent years. Drugs are cleared rapidly from the nasal cavity after intranasal administration, resulting in rapid systemic drug absorption. Several approaches are here discussed for increasing the residence time of drug formulations in the nasal cavity, resulting in improved nasal drug absorption. The article highlights the importance and advantages of the drug delivery systems applied via the nasal route, which have bioadhesive properties. Bioadhesive, or more appropriately, mucoadhesive systems have been prepared for both oral and peroral administration in the past. The nasal mucosa presents an ideal site for bioadhesive drug delivery systems. In this review we discuss the effects of microspheres and other bioadhesive drug delivery systems on nasal drug absorption. Drug delivery systems, such as microspheres, liposomes and gels have been demonstrated to have good bioadhesive characteristics and that swell easily when in contact with the nasal mucosa. These drug delivery systems have the ability to control the rate of drug clearance from the nasal cavity as well as protect the drug from enzymatic degradation in nasal secretions. The mechanisms and effectiveness of these drug delivery systems are described in order to guide the development of specific and effective therapies for the future development of peptide preparations and other drugs that otherwise should be administered parenterally. As a consequence, bioavailability and residence time of the drugs that are administered via the nasal route can be increased by bioadhesive drug delivery systems. Although the majority of this work involving the use of microspheres, liposomes and gels is limited to the delivery of macromolecules (e.g., insulin and growth hormone), the general principles involved could be applied to other drug candidates. It must be emphasized that many drugs can be absorbed well if the contact time between formulation and the nasal mucosa is optimized.

Systemic availability (Lung deposition) of drug from two different dry-powder inhalers in children with asthma

Systemic availability (Lung deposition) of drug from two different dry-powder inhalers in children with asthma

Comparing oral and intramuscular administration of medetomidine in cats

Medetomidine (200 μg/kg) was administered orally and, on a seperate occasion, im to 7 cats. Peak serum drug concentrations were reached more slowly after oral (43.6 ± 14.3 min) than after im administration (21.6 ± 10.0 min). The onset of sedation and recumbency lagged after oral administration. There were no statistically significant differences between the 2 routes of administration in peak serum concentrations, systemic drug availability or extent of sedation. However, there was considerable variation in these parameters between individuals after oral administration. The extent of salivation correlated negatively with systemic drug availability after oral administration. Where excessive salivation did not occur, systemic drug availability and the depth of sedation were comparable to, or even higher than, were obtained after the corresponding im administrations. In conclusion, oral administration of medetomidine induced a clinical sedation but, when accurate dosing is a necessity, the oral route may not be very reliable due to possible drug losses through salivation.

Importance of dissolution process on systemic availability of drugs delivered by colon delivery system

The relationship between in vitro drug release characteristics from colon delivery systems and in vivo drug absorption was investigated using three kinds of delayed-release systems. 5-aminosalicylic acid (5-ASA), tegafur (FT) and carbamazepine (CBZ) were selected as model drugs. Pressure-controlled colon delivery capsules (PCC) for liquid preparations, time-controlled colon delivery capsules (TCC) for liquid and solid preparations and Eudragit S coated tablets for solid preparations were used in this study. At first, in vitro dissolution tests for all preparations were performed. Drug release from solid preparations was delayed compared to that from liquid preparations with all three drugs. Next, these preparations were administered to fasted beagle dogs. For 5-ASA, the mean C maxs (peak level) of Eudragit S coated tablets and PCC were 5.52 and 16.89 μg ml −1, respectively. The mean T maxs (time when drug reached peak level) were 3.0 and 5.3 h. AUCs were 22.57 and 48.09 μg·h ml −1, respectively. For FT, C maxs of Eudragit S coated tablet and PCC were 0.87 and 1.46 μg ml −1, and T maxs were 7.0 and 6.7 h, respectively. AUCs were 9.73 and 15.55 μg·h ml −1 and bioavailabilities were 43.79 and 70.84%. For CBZ, the mean C maxs of liquid preparations and solid preparations were 0.37 and 0.22 μg ml −1, respectively. The mean T maxs were 4.7 and 4.3 h. AUCs were 0.673 and 0.392 μg·h ml −1. With liquid preparations, drug was thought to contact to the colonic membrane easily because of lack of interference by stools, and to be absorbed well as compared with solid preparations. From these findings, drug release from colon delivery systems and drug dissolution in the colonic lumen are very important factors for the systemic availability of drugs from the colon delivery systems.

Transfersomes-mediated transepidermal delivery improves the regio-specificity and biological activity of corticosteroids in vivo

Innovative, carrier-based suspensions of several commonly used corticosteroids are introduced. These formulations contain the recently developed agent carriers, transfersomes, which are sufficiently deformable to penetrate into or across the intact skin barrier. The resulting drug delivery can be varied systematically: depending on the precise application conditions and carrier design, between 100% and ≤5% of applied drug is deposited in the outermost skin region. Low area dose favors the drug retention in the skin and keeps the relative area under the curve for the blood pool below a few per cent, at most, of that resulting from the corresponding drug injection. Transfersomes hence improve the specificity of topical drug delivery and the overall drug safety. Increasing the total applied drug dose, as well as the dose per area, promotes the systemic drug availability. After an epicutaneous application of sufficient drug amount, therapeutically meaningful agent concentration is reached in the blood. This normally happens after the lag time of approximately 4 h to 6 h. When hydrocortisone, dexamethasone, or triamcinolone-acetonide are administered epicutaneously in transfersomes, for example, at the dose of 1.5 mg/kg, 1.5 mg/kg, and 1 mg/kg, the respective concentrations of these drugs in the blood at t=8 h are approximately 0.4 μg/ml, near 0.75 μg/ml and 0.007 μg/ml. These results are comparable to those of a subcutaneous injection of (3–10×) lower amounts of the same drug. Concentration of the epicutaneously administered corticosteroids in the blood is always lower than in the skin, whereas 28 μg/g, 156 μg/g, and 10 μg/g are found for the above mentioned drug doses at t=8 h, respectively. Transfersome-based corticosteroids are biologically active at doses several times lower than that currently used in the dermatic formulations for the treatment of skin diseases. The biological anti-edema activity of transfersomal corticosteroid formulations hence exceeds that of the corresponding commercial products, probably owing to the superior drug-targeting potential in the organ.