Topical Vehicle Research Articles

Effect of topical vasoconstrictor exposure upon tumoricidal radiotherapy

Topical application of the alpha adrenergic vasoconstrictors norepinephrine, phenylephrine or epinephrine to skin or mucosa in alcohol:water-based delivery vehicles minutes before irradiation has recently been shown to protect skin and mucosa cells against radiotherapy-induced toxicities in both preclinical and clinical studies. The protective mechanism is thought to involve transient skin or mucosal vasoconstriction with secondary, transient hypoxia and associated radioprotection. Regarding possible protection of tumor cell nests within the radiotherapy field, the endothelial cell-abnormal stroma constructed blood vessels generally found in human tumors commonly lack adrenergic receptor-containing smooth muscle cells that are required to achieve vasoconstriction. Consistent with this, we show here that topical application of norepinephrine or phenylephrine to broken or intact skin over human Cal-27 or A-431 xeonograft, or mouse solid L1210 allograft tumors growing subcutaneously in nude mice, showed no effect upon radiation-induced tumor growth inhibition. Although vasoconstrictor-induced nude mouse skin blanch was seen minutes after topical application of 600 mM norepinephrine, no blanching was seen within the A-431 xenograft tumors. Radiation dermatitis was severe 11 days post-irradiation (2 × 13.8 Gy) in the irradiated field containing xenograft tumors in mice that received topical delivery vehicle, but was absent in mice that received topical norepinephrine. Topical vasoconstrictor-conferred prevention of radiation dermatitis without discernible radioprotection of three histologically diverse xenograft or allograft tumors supports further development of the topical vasoconstrictor therapeutic strategy in humans.

Effect of the Various Solvents on the <i>In Vitro</i> Permeability of Vitamin B<sub>12</sub> through Excised Rat Skin

Purpose: To investigate the effect of different solvents on the in vitro skin permeability of vitamin B 12 . Method: Vitamin B 12 (B 12 ) permeability experiments through rat skin pretreated with various solvents namely, propylene glycol, oleoyl macrogol-6-glycerides, propylene glycol monocaprylate and oleic acid, were performed in Franz diffusion cells and compared with hydrated rat skin as control. The permeability parameters evaluated include steady-state flux (J ss) , lag time (T lag ), permeability coefficient (Kp) and diffusion coefficient (D). The solvents’ permeability enhancement mechanisms were investigated by comparing of changes in peak position and their intensities of assymmetric (Asy) and symmetric (Sym) C-H stretching, and C=O stretching absorbance using Fourier transform infrared spectroscopy (FTIR), as well as by comparing mean transition temperature (Tm) and their enthalpies (∆H) using differential scanning calorimetery (DSC). Results: All the solvents significantly decreased diffusion coefficient (p < 0.05), with capryol showing the greatest enhancement ratio (ER D) based on diffusion coefficient followed by labrafil, oleic acid and propylene glycol. Flux enhancement ratio (ER flux ) for all the solvents was < ER D. The solubility of B12 in stratum corneum was the rate-limiting step in partitioning. All solvents with different lipophilic properties decreased drug solubility in the stratum corneum and hence lowered partitioning and flux. FTIR and DSC results showed lipid fluidization and extraction by labrafil and capryol, disruption of lipid structure and fluidization by oleic acid, and interaction with stratum corneum keratin by propylene glycol. Conclusion: Water is a suitable topical vehicle for B 12 as it can increase partitioning and diffusion through rat skin.

Direct comparison of laser Doppler flowmetry and laser Doppler imaging for assessment of experimentally-induced inflammation in human skin

Laser Doppler imaging (LDI) and laser Doppler flowmetry (LDF) can measure localized skin perfusion. The purpose of the study was to directly compare LDF with LDI as a tool for measuring skin blood changes in an experimental model of chemically-induced skin inflammation. Regions of interest 1.8 cm² in area on the forearm skin of eight healthy volunteers were randomized and exposed to 0.25, 0.5, 1, or 2 % topical sodium lauryl sulfate (SLS) or vehicle for 24 h. Mean blood flow was measured by LDI and LDF at 24, 48, and 72 h. Inflammation was clinically graded using a standardized, clinical score. Sodium lauryl sulfate induced significant, dose-dependent local inflammation. Both Doppler methods were significantly correlated with the clinical grading (LDF, r = 0.755; LDI, r = 0.836). LDF and LDI showed similar significance differences with regard to dose- and time-response patterns compared to the vehicle. The absolute and relative LDF and LDI values were significantly correlated. Laser Doppler flowmetry and LDI showed similar dose- and time-response relations in irritant-induced inflammatory skin reactions. For the assessment of localized skin reactions, LDI possesses no apparent advantages over the less expensive LDF method for grading dermal inflammatory reactions.

Critical Role of Transforming Growth Factor Beta in Different Phases of Wound Healing

This review highlights the critical role of transforming growth factor beta (TGF-β)1-3 within different phases of wound healing, in particular, late-stage wound healing. It is also very important to identify the TGF-β1-controlling factors involved in slowing down the healing process upon wound epithelialization. TGF-β1, as a growth factor, is a known proponent of dermal fibrosis. Several strategies to modulate or regulate TGF's actions have been thoroughly investigated in an effort to create successful therapies. This study reviews current discourse regarding the many roles of TGF-β1 in wound healing by modulating infiltrated immune cells and the extracellular matrix. It is well established that TGF-β1 functions as a wound-healing promoting factor, and thereby if in excess it may lead to overhealing outcomes, such as hypertrophic scarring and keloid. Thus, the regulation of TGF-β1 in the later stages of the healing process remains as critical issue of which to better understand. One hypothesis is that cell communication is the key to regulate later stages of wound healing. To elucidate the role of keratinocyte/fibroblast cross talk in controlling the later stages of wound healing we need to: (1) identify those keratinocyte-released factors which would function as wound-healing stop signals, (2) evaluate the functionality of these factors in controlling the outcome of the healing process, and (3) formulate topical vehicles for these antifibrogenic factors to improve or even prevent the development of hypertrophic scarring and keloids as a result of deep trauma, burn injuries, and any type of surgical incision.

Effect of non–phospholipid-based cationic and phospholipid-based anionic nanosized emulsions on skin retention and anti-inflammatory activity of celecoxib

Context: Celecoxib (CXB, 0.2 g)-loaded anionic and cationic nanosized emulsions were prepared by a well-established combined emulsification method.Objectives: To investigate the effect of non–phospholipid-based cationic and phospholipid-based anionic emulsions on skin retention and anti-inflammatory activity of CXB.Methods: Using Keshary-Chien diffusion cells with cellulose acetate membrane or excised rat skin, in vitro release and skin retention of CXB from solution and emulsions were studied. The anti-inflammatory activity was evaluated by the carrageenan-induced hind paw edema method in Wistar rats.Results: The amount of drug released through artificial membrane has decreased from 122.00 ± 0.70 μg/cm2 for the CXB solution to 55.80 ± 0.70 μg/cm2 for anionic emulsion, and then further decreased to 24.79 ± 0.90 μg/cm2 for cationic emulsion. The JSS value obtained with solution, anionic, and cationic emulsions were 6825.79 ± 920.86, 2513.15 ± 382.71, and 1925.67 ± 147.42, respectively. Cationic emulsion showed a significantly higher level (P ≤ 0.05) of drug accumulation in full-thickness rat skin than anionic emulsion, and a substantially lesser percentage inhibition of edema values compared with both solution and anionic emulsion.Discussion and conclusion: Sustained drug release together with increased skin accumulation and simultaneously decreased skin permeation as observed with cationic emulsion should substantiate its suitability as a topical delivery vehicle for CXB.

A phase II study of photodynamic therapy (PDT) with aminolevulinic acid HCl (ALA) 20% topical solution + blue light versus aminolevulinic acid HCl topical solution vehicle (VEH) + blue light for the treatment of actinic keratoses (AKs) on the upper extremi

A phase II study of photodynamic therapy (PDT) with aminolevulinic acid HCl (ALA) 20% topical solution + blue light versus aminolevulinic acid HCl topical solution vehicle (VEH) + blue light for the treatment of actinic keratoses (AKs) on the upper extremi

A phase II study of photodynamic therapy (PDT) with aminolevulinic acid HCl (ALA) 20% topical solution + blue light vs ALA topical solution vehicle + blue light using spot and broad area application and incubation times of 1, 2 and 3 hours for the treatment

A phase II study of photodynamic therapy (PDT) with aminolevulinic acid HCl (ALA) 20% topical solution + blue light vs ALA topical solution vehicle + blue light using spot and broad area application and incubation times of 1, 2 and 3 hours for the treatment

A Novel Vehicle Formulation for Treatment of Inflammatory Skin Diseases

Objective: To test the efficacy of a new topical vehicle formulation containing cetirizine in emu oil in treating inflammatory skin conditions. Methods: A single blind half body comparative study of patients with psoriasis, atopic and stasis dermatitis were all treated with midpotency topical steroid (desoximethasone) in propylene glycol base, desoximethasone and cetirizine in propylene glycol base, desoximethasone in emu oil base and desoximethasone with cetirizine dissolved in emu oil. Results: Based on patients’ ranking of creams’ efficacy, and supported by photographic data and investigators’ clinical assessment, results clearly indicated that desoximethasone and cetirizine in emu base was statistically more efficacious than either desoximethasone alone or with cetirizine in neutral propylene glycol base or desoximethasone in emu oil base (without cetirizine). Conclusions: Cetirizine and emu oil, having inherent anti-inflammatory and other beneficial properties synergistically, and by different biochemical pathways, enhance and magnify each other’s pharmaceutical effects that are useful in treatment of skin inflammatory diseases.

Influence of psoriatic arthritis on the efficacy of adalimumab and on the treatment response of other markers of psoriasis burden: subanalysis of the BELIEVE study

Adalimumab is a fully human anti-TNF monoclonal antibody with demonstrated efficacy and safety in patients with moderate to severe psoriasis and psoriatic arthritis (PsA). This study examined the effect of PsA on adalimumab treatment response in patients from the Phase IIIb BELIEVE trial (NCT00574249, ClinicalTrials.gov registry), and response of other markers of disease burden to adalimumab treatment. In this post hoc analysis, patients with or without a history of PsA and with moderate to severe psoriasis were randomized to adalimumab plus adjunctive topical therapy (calcipotriol/betamethasone dipropionate) or monotherapy (adalimumab plus matching topical vehicle). Regardless of baseline PsA, improvement at Week 16 was seen in PASI 75, pruritus, PSSI, and DLQI (all patients), and mean NAPSI scores. Patients with PsA had HAQ improvement at Week 16, and compared to patients without PsA, had higher VAS pain scores. This analysis represents the first publication of the influence of PsA and PsA plus body weight on patient response to adalimumab, and response of scalp psoriasis, nail psoriasis, and patient-reported outcomes to adalimumab. The incidence of AEs was similar among all patients (62%), those with PsA (65%) and without PsA (60%). The most common AEs were infections (27%); 4.2% of all patients reported serious AEs. Adalimumab treatment resulted in comprehensive, clinically relevant improvements from baseline PsA status, in skin, nails, quality of life, pain and pruritus. Despite having more severely affected disease and quality of life, patients with PsA did not respond to adalimumab significantly differently from patients without PsA.

Validating topical skin therapies in randomised controlled studies

TOPICAL therapy has played an important role in the management of allergic and infectious skin diseases in human medicine for a long time (Callen and others 2007, Simpson 2010). There...

Monocyte development inhibitor PRM-151 decreases corneal myofibroblast generation in rabbits

This study investigated whether PRM-151 (Promedior, Inc., Malvern, PA), a recombinant form of human pentraxin-2 (PTX-2, also referred to as serum amyloid P, hSAP), that inhibits differentiation of circulating monocytes into fibrocytes and profibrotic macrophages, could modulate generation of myofibroblasts after opacity-producing corneal injury in rabbits, and, therefore, have potential to reduce or prevent haze after PRK. Nine diopter PRK for myopia was performed with the VISX S4 IR laser. Four groups of 6 animals were treated in masked fashion: Group 1: 30 μl of topical PRM-151 (20 mg/ml) 6 times a day for 5 days; Group 2: 30 μl topical vehicle 6 times a day for 5 days; Group 3: 200 μl sub-conjunctival PRM-151 (total injection of 4 mg) immediately after surgery and every other day until day 8; Group 4: 200 μl sub-conjunctival injections of vehicle according to the same schedule as group 3. At one month after PRK, the animals were euthanized and immunohistochemistry was performed for the myofibroblast marker α-smooth muscle actin (SMA). The density of SMA+ cells/400× field in the central stroma was determined in each cornea. Myofibroblast density at one month after surgery was significantly lower (p = 0.006) after sub-conjunctival PRM-151 treatment (5.8 ± 2.8 cells/400× stromal field) compared to sub-conjunctival vehicle treatment (15.3 ± 2.9 cells/400× stromal field). There was no significant (p = 0.27) decrease in stromal myofibroblasts triggered by topical PRM-151 treatment (11.8 ± 6.6 cells/400× stromal field) compared to the topical vehicle treatment (14.2.8 ± 6.2 cells/400× stromal field). PRM-151 inhibits myofibroblast generation when administered by sub-conjunctival injection, but not when administered topically, after opacity-producing corneal injury. This study provides additional confirmation that bone marrow-derived cells contribute to corneal myofibroblast generation.

Combination of Microemulsion for Topical Deliverying Tripterygium Wilfordii Multiglycoside

The purpose of this study was to explore the potential application of the combination of microemulsion as a topical delivery vehicle in enhancing the absorption and efficacy of tripterygium wilfordii multiglycoside (TWM). Various microemulsion formulations were developed and an optimal microemulsion (TWM-ME)，which presented spherical droplets and consisted of RH-40, IPM and water was 27: 3.3: 69.7 by weight. It possessd an average droplet size of 23.6 nm, a low viscosity of (3.56±0.12) mm2•s-1 Zeta electric potential was (–5.35±0.42) mV, refractive index was (1.3617±0.0051) nD20, conductivity was (97.6±3.6) μs/cm. Compared to the control solution, TWM-ME provided better skin permeability in vitro. Moreover, TWM-ME has noticeable anti-inflammatory and immune suppression effect. These results indicate that the combination of microemulsion represents an effective vehicle for topical delivery of TWM.

Continuous shear, viscoelastic and spreading properties of a new topical vehicle, FAPG base

Abstract The rheology of a new topical vehicle FAPG base was investigated over the temperature ranges of 25–37°. Continuous shear rheograms obtained with a Ferranti-Shirley cone and plate viscometer were hysteresis loops with spur points; loop areas, yield values and apparent viscosities decreased with increase in temperature and an activation energy for viscous flow of 10.4 kcal mol−1 (43.5 kJ mol−1) was derived. In creep (concentric cylinder geometry) the base was viscoelastic with a low limit of linearity with respect to strain. Creep compliance curves showed an initial elastic response, a region of retarded elasticity and a viscous region; compliances increased and viscosities decreased with temperature rise. Patient acceptance of skin spreadability of the base was assessed using a master curve concept; the spreading properties were close to the preferred values for maximum patient acceptance. It is concluded that FAPG base deserves further study as a vehicle for dermatological use.

The Effect of Semi-Permeable Film Covers on the Biovailability of Betamethasone Valerate Delivered from A Topical Cream Vehicle

The Effect of Semi-Permeable Film Covers on the Biovailability of Betamethasone Valerate Delivered from A Topical Cream Vehicle

Efficacy and safety of adalimumab in patients with psoriasis previously treated with anti‐tumour necrosis factor agents: subanalysis of BELIEVE

Few large clinical studies have evaluated whether switching tumour necrosis factor antagonists (anti-TNFs) is likely to improve psoriasis in patients with prior anti-TNF treatment. The aim of this subanalysis of the BELIEVE study was to assess the efficacy and safety of adalimumab for psoriasis in patients with and without previous anti-TNF treatment. The BELIEVE study enrolled patients with moderate to severe psoriasis and prior failure, intolerance or contraindication to ≥2 systemic therapies. In this 16-week, double-blind, randomized, controlled trial, patients received adalimumab (80 mg, week 0; 40 mg every other week, weeks 1-15) with either topical vehicle or topical calcipotriol/betamethasone dipropionate (C/B) applied once daily for 4 weeks, then as needed. The primary endpoint was ≥75% improvement from baseline in Psoriasis Area and Severity Index score (PASI 75) at week 16. This post hoc subanalysis evaluated the safety and efficacy of adalimumab, with and without topical therapy, in BELIEVE patients who had prior exposure to anti-TNFs. Of 730 patients enrolled, 282 (38.6%) had prior anti-TNFs and 448 (61.4%) were anti-TNF-naïve. Combining topical vehicle and topical C/B study populations, 61.7% of patients with prior anti-TNFs achieved PASI 75 at week 16, compared with 71.7% of anti-TNF-naïve patients (P=0.095). Adalimumab resulted in clinically meaningful improvement regardless of which prior anti-TNF agent had been used, the number of prior anti-TNFs tried, or reasons for discontinuation of prior anti-TNF therapy. Adverse event incidences were similar between patients with and without prior anti-TNF therapy. Adalimumab was effective and well-tolerated in patients with psoriasis previously treated with anti-TNF therapy.

Natural Surfactant-Based Emulsion Vehicles: A Correlation Between Colloidal Structure and In Vitro Release of Diclofenac Diethylamine

The need for an official pharmaceutical vehicle or carrier of drug based on natural sugar emulsifiers that protect and regenerate natural barriers of the skin lipid layer is constantly increasing. This article studies the specific structures of emulsions and two manners of water binding that provide prolonged skin moisturization and delayed or prolonged release of drugs insoluble in water. Natural emulsifiers of an alkylpolyglucoside (cetearyl alcohol and cetearyl glycoside) and estar-type (sorbitan stearate and sucrose cocoate) are used for manufacturing vehicle/carriers of drugs (diclofenac diethylamine). Specific hydrofilic groups in emulsifiers, such as glycozide and ester, are capable of binding in different manners and variable quantities of water by hydrogen bonds within the cream, which is responsible for water distribution and prolonged skin moisturization. This lyotropic potential of natural emulsifiers—alkylpolyglucoside and estar type—may affect the physical stability of topical vehicles by determining the colloidal structure, further reflecting the drug delivery from the pharmaceutical excipient to the skin. The aim of this article is to evaluate whether the type of emulsifier influences the structural characteristics of emulsion systems and how the content and availability of water within the cream reflects the delivery of diclofenac diethylamine (1.16%) from the topical vehicles. Freeze-fracture transmission electron microscopy, wide-angle x-ray diffraction, thermogravimetric analysis, and continual and oscilatory rheological measurements are employed for characterization of emulsion system colloidal structure. Diclofenac diethylamine release profiles from investigated emulsion systems were evaluated using the rotation paddle apparatus, modified by addition of diffusion cells (enhancer cell). There is an important difference in water distribution within the creams with emulsifiers of different chemical types. In the sample with ester-type sugar emulsifiers, the quantity of interlamellar-bound water is four times less than bulk and secondary water, while in the sample with alkylpolyglucoside emulsifier, approximately two thirds of total water are bound inside the system and one third is poorly bound, that is, bulk water. It can also be seen that diclofenac diethylamine is gradually released from the vehicle during 6 hours of testing. Formulation of topical vehicle as dermopharmaceutical drug carrier system, with natural emulsifier, like cetearyl alcohol, cetearyl glucoside, sorbitan stearate, and sucrose cocoate, is recommended.

Topical Delivery of Interferon Alpha by Biphasic Vesicles: Evidence for a Novel Nanopathway across the Stratum Corneum

Noninvasive delivery of macromolecules across intact skin is challenging but would allow for needle-free administration of many pharmaceuticals. Biphasic vesicles, a novel lipid-based topical delivery system, have been shown to deliver macromolecules into the skin. Investigation of the delivery mechanism of interferon alpha (IFN alpha), as a model protein, by biphasic vesicles could improve understanding of molecular transport through the stratum corneum and allow for the design of more effective delivery systems. The interaction of biphasic vesicles with human skin and isolated stratum corneum membrane was investigated by confocal microscopy, differential scanning calorimetry (DSC) and small- and wide-angle X-ray scattering (SAXS and WAXS). Confocal microscopy revealed that biphasic vesicles delivered IFN alpha intercellularly, to a depth of 70 microm, well below the stratum corneum and into the viable epidermis. DSC and SAXS/WAXS data suggest that the interaction of biphasic vesicles with SC lipids resulted in the formation of a three-dimensional cubic Pn3m polymorphic phase by the molecular rearrangement of intercellular lipids. This cubic phase could be an intercellular permeation nanopathway that may explain the increased delivery of IFN alpha by biphasic vesicles. Liposomes and submicrometer emulsion (the individual building blocks of biphasic vesicles) separately and methylcellulose gel, an alternative topical vehicle, did not induce a cubic phase and delivered low amounts of IFN alpha below the stratum corneum. Molecular modeling of the cubic Pn3m phase and lamellar-to-cubic phase transitions provides a plausible mechanism for transport of IFN alpha. It is hypothesized that induction of a Pn3m cubic phase in stratum corneum lipids could make dermal and transdermal delivery of other macromolecules also possible.

Physically cross-linked chitosan hydrogels as topical vehicles for hydrophilic drugs.

Physically cross-linked chitosan hydrogels with lauric, myristic, palmitic or stearic acid were prepared by freeze-drying and have been studied for topical use. This study selected propranolol hydrochloride as a hydrophilic model drug to design a transdermal delivery system. We evaluated the effect of the nature of the cross-linker on drug permeation through porcine skin and the main permeation parameters (diffusion coefficient, flux and lag time) were calculated. All the chitosan hydrogels analysed provided more transcutaneous permeation of propranolol hydrochloride than the corresponding solution of the commercial drug. Among the different chitosan vehicles, chitosan-laurate and chitosan-myristate hydrogels enhanced lyophilised drug diffusion through the skin with respect to chitosan-palmitate and chitosan-stearate hydrogels. This can been explained by the interaction of the hydrogels with the stratum corneum, increasing the solubility of the drug in the skin.

Investigation of the absorption of hypericin into the skin of hairless mice.

The skin absorption of hypericin was evaluated in hairless mice to develop an optimised hypericin topical formulation that could be used in the clinical study of psoriasis. Hypericin (0.01-1.0%) in Beeler basis, polyethylene glycol ointment, carbopol gel, cetomacrogol cream, petrolatum or emulsifying ointment, with and without skin-absorption enhancers (isopropylidene glycerol and diethylene glycol monoethyl ether), was tested in-vivo on hairless mice skin. Using a skin-stripping technique and the intrinsic fluorescence of hypericin under standardised UV365 irradiation, it was demonstrated that the absorption of hypericin very much depended on the vehicle used. The concentrations of hypericin in the skin were then estimated by HPLC analysis. For this purpose, two vehicles were employed, with which hypericin penetrated the skin of hairless mice well (emulsifying ointment with isopropylidene glycerol) or very poorly (polyethylene glycol ointment). In the case of emulsifying ointment with isopropylidene glycerol (0.05% hypericin), a substantial concentration of hypericin (8.6+/-3.2 microg g(-1)) (mean +/- s.d., n = 5) was found in the skin. With polyethylene glycol ointment, however, only a limited hypericin skin concentration (0.38+/-0-34 microg g(-1), n = 5) was achieved. These results show that emulsifying ointment with polyethylene glycol holds promise as an effective topical vehicle for the treatment of skin diseases, such as psoriasis, with hypericin.

Topical piroxicam in vitro release and in vivo anti-inflammatory and analgesic effects from palm oil esters-based nanocream

IntroductionDuring recent years, there has been growing interest in use of topical vehicle systems to assist in drug permeation through the skin. Drugs of interest are usually those that are problematic when given orally, such as piroxicam, a highly effective anti-inflammatory, anti-pyretic, and analgesic, but with the adverse effect of causing gastrointestinal ulcers. The present study investigated the in vitro and in vivo pharmacodynamic activity of a newly synthesized palm oil esters (POEs)-based nanocream containing piroxicam for topical delivery.MethodsA ratio of 25:37:38 of POEs: external phase: surfactants (Tween 80:Span 20, in a ratio 80:20), respectively was selected as the basic composition for the production of a nanocream with ideal properties. Various nanocreams were prepared using phosphate-buffered saline as the external phase at three different pH values. The abilities of these formulae to deliver piroxicam were assessed in vitro using a Franz diffusion cell fitted with a cellulose acetate membrane and full thickness rat skin. These formulae were also evaluated in vivo by comparing their anti-inflammatory and analgesic activities with those of the currently marketed gel.ResultsAfter eight hours, nearly 100% of drug was transferred through the artificial membrane from the prepared formula F3 (phosphate-buffered saline at pH 7.4 as the external phase) and the marketed gel. The steady-state flux through rat skin of all formulae tested was higher than that of the marketed gel. Pharmacodynamically, nanocream formula F3 exhibited the highest anti- inflammatory and analgesic effects as compared with the other formulae.ConclusionThe nanocream containing the newly synthesized POEs was successful for trans-dermal delivery of piroxicam.