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Aim: To evaluate the effect of the implant’s thread cross sectional design on the micromotion of the implants in different bone qualities. Materials and methods: In this finite element analysis study, four implant models exhibiting four different thread designs were created using Solidworks software. Each model was assembled in four different bone quality models resulting in 16 groups. Each group was examined for micromotion under 100N force using ANSYS software. Results: D1 bone showed the lowest micromotion while D4 bone showed the highest, regardless the thread design. In D1 and D2 bone, v-shaped thread showed the lowest micromotion, which was lower than the square thread and the buttress was lower than the reverse buttress. While in D3 and D4 bone, the lowest micromotion was observed with the square thread, which was lower than the v-shaped and the reverse buttress thread was lower than the buttress thread. Conclusion: Micromotion decreases as the bone quality increases irrelevant of the implant thread design. In D1 and D2 bone, the best thread to be used is the v-shaped thread, while in D3 and D4 bone, the best is the square shaped thread.

Nasal drug delivery has the potential to improve the systemic bioavailability of drugs with low oral bioavailability. Olmesartan medoxomil (OLM) is one of the most popular drugs for the treatment of hypertension with poor oral bioavailability of approximately 26 %. In this context, the goal of this work was to synthesize chitosan nanoparticles (CS NPs) loaded with OLM using the ionotropic gelation method to enhance the bioavailability and decrease oral side effects through nasal route. The particle size (PS), zeta potential (ZP), entrapment efficiency (%EE), and ex-vivo transmucosal permeation study of CS NPs were all evaluated. The pharmacokinetic and pharmacodynamic studies of selected formula compared to oral and nasal OLM suspensions were conducted. Successful formation of spherically shaped OLM CS NPS in the nano-range (240.02-344.45 nm) favorable for the intranasal absorption with high %EE (75.2-83.51 %) was achieved. The ability of OLM CS NPs to permeate efficiently across the nasal mucosa was proven in an ex vivo permeation experiment. Pharmacokinetic study demonstrated that the intranasal administration of OLM CS NPs exhibited improved bioavailability by 11.3-folds relative to oral OLM suspension as indicated by higher AUC value. The superior effect of intranasal OLM CS NPs was also accentuated in l-NAME induced hypertensive rats compared to intranasal and oral OLM suspension by reducing the high blood pressure (BP) and improving the heart rate (HR) of the induced group. Histological examinations revealed no damage occurred to nasal mucosa. In conclusion, OLM CS NPs had the ability to significantly improve the bioavailability of OLM and decrease BP and HR, suggesting the potential application of CS NPs as a promising carrier for the systemic delivery of OLM via intranasal route.

This study was designed to optimize the effect of operating conditions and formulation parameters using various additives to develop α-amylase nanoparticles. α-Amylase was chosen due to its importa...

This work aimed to develop an antifungal vaginal sponge loaded with butoconazole nitrate (BN). Sponges were prepared by lyophilization of different polymers (chitosan, gelatin, hydroxyl propyl methylcellulose (HPMC) and carbopol 934) with calcium chloride as crosslinking agent, sodium carboxymethylcellulose as viscosity modifier and different solubilizers. They were characterized regarding morphology, tensile force, elongation percentage, swelling index and their drug release properties. Mucoadhesion force and residence time with cow vaginal mucosa were also determined. The selected formulae were examined using Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), the scanning electron microscope (SEM), stability and antifungal activity against Candida albicans. Results revealed that all sponges biodegraded completely within 24 h. Chitosan sponges exhibited favorable values and in-vitro drug release. Selected chitosan sponges were stable for three months regarding their physical properties and their release profile. Agar diffusion susceptibility test revealed that chitosan: HPMC (1: 1) with 1.5% w/v Tween 80- sponge was the most effective in term of fungal eradication compared to other sponges and plain drug as well. The results suggested that this mucoadhesive system could be a very promising alternative for other commercially available vaginal antifungal dosage forms, with longer residence time and improved patient compliance.

A nanoemulsion system was designed for Atorvastatin calcium (ATOR) transdermal delivery to overcome its poor bioavailability of (30%) resulting from the extensive first-pass effect and dissolution rate-limited in vivo absorption. Pseudo ternary phase diagrams were developed, and various NE formulae were prepared using oleic acid (OA), Tween 80 as surfactant and PEG 400 as cosurfactant, ethanol and limonene as permeation enhancers (PEs). NEs were characterized for morphology, droplet size, zeta potential and in vitro release. The optimized formulae were assessed for ex vivo transdermal permeation and in vivo pharmacodynamic/pharmacokinetic studies. Hypocholesterolemic effect after 7 days skin treatment was detected and compared to oral ATOR dispersion. Finally, blood plasma levels were measured for 24 h for rats received the selected transdermal NE and transdermal drug in OA. The obtained results suggested the low potentiality of NE systems in transdermal delivery of lipophilic drugs, only the addition of PEs is driving factor for increasing drug flux through full thickness rat skin. In the optimized formula, the presence of ethanol and PEG 400 disrupts SC lipids exhibiting rapid ex vivo release profile compared to other NEs and to ATOR in OA. In contrast, the optimized NE achieved a prolonged plasma profile. Transdermal NE was significantly more efficient than oral administration in lowering cholesterol plasma level and in increasing ATOR bioavailability. In conclusion, data revealed no correlation between ex vivo and in vivo studies explained by the collapse of the follicles in ex vivo skin permeation study, leaving only the lipoidal pathway for NE to pass through, thus only NE components, neither nanosizing nor other reported mechanisms, are the main influencing factors. In vivo experiments suggested that o/w NE changed ATOR pathway to follicular delivery leading to accumulation of NE in follicles and consequently a prolonged plasma profile.

Terbinafine Hcl (TB) is a poorly water soluble antifungal drug. Topical nanoemulsion based gel containing TB was prepared with a view to improve its solubility and antifungal activity. In preparation of the nanoemulsion (NE), excipients were selected based on the solubility study. Peceol was optimized as the oil phase. Tween 80 and propanol were optimized as the surfactant and co-solvent respectively, and were mixed (Smix) in different weight ratios (1:1, 1:2, 1:3, 1:4, 4:1, 3:1 and 2:1, respectively). Pseudoternary phase diagrams were developed and Pecol and Smix were mixed in different weight ratios ranging from 1:9 to 9:1. Based on the NE region of each diagram, the formulae were selected. The formulated nanoemulsions were characterized and evaluated for in vitro drug release and thermodynamic stability. The optimum nanoemulsion formulae containing 10 or 15% w/w oil, 45% w/w Smix (1:2/1:3) and 45-40% w/w aqueous phase) were incorporated into Carbopol 940 gel bases forming three different TB nanoemulsion based emulgel formulae (F1-F3) which were examined for ex vivo drug permeation and in vivo antifungal activity compared to the marketed product; Lamisil® emulgel. The results showed that TB skin permeation from all the prepared nanoemulsion based gel formulae was significantly (p

In an attempt to optimize the anti- hyperlipidemic effect and reduce statins induced hepatotoxicity, Atorvastatin Calcium (ATC) transdermal proniosomal gel (PNG) was developed. Different non-ionic surfactants (NISs) (Spans, Tweens, Cremophor RH 40 and Brij 52) were incorporated in the vesicle's lipid bilayer, in combination with lecithin. PNG formulae were characterized for encapsulation efficiency percent (% EE), vesicle size, polydispersity index (PDI) and zeta potential (ZP). Ex-vivo permeation study was performed using full thickness rat skin measuring drug flux and skin permeability coefficients. The pharmacodynamic performance of optimized transdermal ATC- PNG on both lipid profile and liver biomarkers was assessed and compared to oral ATC administration in poloxamer 407-induced hyperlipidemic rats. The liver tissues were subjected to histological examination as well. The results revealed nano-size range vesicles with relatively high ATC entrapment efficiency. Ex-vivo results demonstrated the permeation superiority of ATC proniosomes over free drug. Pharmacodynamic study revealed that transdermal administration of ATC- PNG succeeded in retaining the anti-hyperlipidemic efficacy of orally administered ATC without elevating liver biomarkers. The histological examination signified the role of optimized ATC-PNG in hindering statin- induced hepatocellular damage. The obtained results suggested a promising, easy-to-manufacture and effective ATC proniosomal gel for safe treatment of hyperlipidemia.

One of the main challenges for using Tamoxifen citrate (TMC) in breast cancer therapy is achieving proper target and efficient delivery of adequate concentration to the adenocarcinoma without harming healthy glandular and soft fatty tissue. Herein, TMC niosomal thermosensitive hydrogels were proposed as a tool to resolve this challenge. Niosomes were prepared by film hydration technique and incorporated into Pluronics thermosensitive gels prepared using cold method. The prepared hydrogels were evaluated for gelation temperature, rheological behavior and in vitro drug release. Moreover, in vivo anti-tumor activity was examined in Ehrlich carcinoma mice model through reporting solid tumor volume regression and tissue distribution of TMC. Type and ratio of used poloxamers were manipulated to provide the optimal gelation temperature (34–37 °C). Rheological analysis showed low viscosity and elasticity values at low and room temperature while these values significantly increased at the physiological temperature. A prolonged diffusion-driven release of TMC was detected. In vivo data showed, evidently, that anticancer activity was improved with significant retention of the drug at the tumor site. These encouraging results confined that this in situ hydrogel depot offers an attractive approach for controlled delivery of TMC and clinically expected to be useful delivery system in loco-regional therapy for breast cancer.

One of the main challenges for successful pharmaceutical application of Catalase (CAT) is maintaining its stability. Physical immobilization of CAT through nano-encapsulation was proposed to resolve this challenge. CAT encapsulating niosomes (e-CAT) were prepared using Brij® 30, 52, 76, 92, and 97 in the presence of cholesterol (Ch) by thin film hydration method. Niosomes were characterized for encapsulation efficiency % (EE), size, poly-dispersity index (PI), and morphology. Kinetic parameters, pH optimum, thermal stability, and reusability of CAT were determined. The influence of optimized e-CAT dispersion onto thermally injured rat skin was evaluated. Results revealed that encapsulation enhanced CAT catalytic efficiency (Vmax/Km). Free CAT and e-CAT had pH optimum at 7.0. e-CAT exhibited improved thermal stability where it retained 50% residual activity at 60 °C. Free CAT lost its activity after three consecutive operational cycles; however, e-CAT retained 60% of its initial activity following 12 cycles. After 24 h of topical application on thermal injury, a significant difference in lesion size was observed with e-CAT compared with the control group. Based on these encouraging results, CAT immobilization demonstrated a promising novel delivery system that enhances its operational stability. In addition, nano-encapsulated CAT can be anticipated to be beneficial in skin oxidative injury.

Aims: This study focused on comparing binary and ternary solid dispersions (SD's) of water-insoluble Tamoxifen citrate (TMC) regarding drug dissolution and oral bioavailability. Basically, the enhanced dissolution of this drug by water-soluble polymer has not yet been reported in literature. Study Design: In vitro and In-vivo characterization of Tamoxifen citrate loaded binary and ternary solid dispersion systems. Place and Duration of Study: Department of Pharmaceutics and Industrial Pharmacy, Helwan University, Cairo, Egypt between June 2012 and June 2013. Methodology: Amorphous SD's of TMC with two hydrophilic polymers, polyethylene glycol 6000 (PEG 6000) and Methyl cellulose (MC), were prepared by melting method. Binary SD's of TMC with PEG of different weight ratios were prepared. MC was used as third component to prepare ternary SD's. Physicochemical properties of SD's were characterized by FTIR, DSC, and In-vitro drug release in comparison with physical mixtures and the drug alone. Oral bioavailability of the optimized SD formula was compared with that of free TMC in rats. Results: Infrared spectroscopic studies suggested no interaction between TMC and Original Research Article British Journal of Pharmaceutical Research, 4(2): 215-229, 2014 216 polymers rather than H-bond formation. A remarkably improved dissolution of drug from the ternary solid dispersion systems when compared to the binary solid dispersion systems was detected. On the basis of % dissolution efficiency (% DE), the SD composed of PEG: TMC: MC in a ratio 4:1:2 w/w/w was selected as the optimized SD. The in-vivo studies showed extremely significant higher values of Cmax (P

The objective of the present study was to formulate and evaluate microemulsion systems for topical delivery of clotrimazole (CTM). The solubility of CTM in various oils was determined to select the oil phase of the microemulsion systems. Pseudoternary phase diagrams were constructed to identify the area of microemulsion existence. Five CTM microemulsion formulations (M1-M5) were prepared and evaluated for their thermodynamic stability, pH, refractive index, droplet size, viscosity, and in vitro release across cellulose membrane. Among the prepared microemulsion formulations, M3 (lemon oil/Tween 80/n-butanol/water) and M4 (isopropyl myristate/Tween 80/n-butanol/water) microemulsion systems were found to be promising according to their physical properties and CTM cumulative percentage release. Gel form of M3 and M4 were prepared using 1% Carbopol 940 as the hydrogel matrix. Both formulations were evaluated in the liquid and gel forms for drug retention in the skin in comparison to the marketed CTM topical cream and their stability examined after storage at 40°C for 6 months. Microemulsion formulations achieved significantly higher skin retention for CTM over the CTM cream. Stability studies showed that M4 preparations were more stable than M3. The in vitro anti-fungal activity of M4 against Candida albicans was higher than that of the conventional cream. Moreover, clinical evaluation proved the efficacy and tolerability of this preparation in the treatment of various topical fungal infections.

The objectives of the present study are to evaluate guar gum in combination with hydroxyl propyl methylcellulose (HPMC) as compression coat for colonic delivery of prednisolone as well as improving the mechanical properties of the compressed coated tablets. The core tablets containing 5 mg prednisolone were compression coated with 125 mg of coating materials consisted of guar gum alone or mixtures of guar gum in combination with different ratios of HPMC. The compressed coated tablets were evaluated for their mechanical properties, in vitro drug release and in vivo performance in human volunteers. The compressed coated tablets with coats containing HPMC exhibited acceptable mechanical properties. In vitro drug release studies in pH 7.4 phosphate-buffered saline medium containing 2% (w/v) rat caecal content have shown that increase in concentration of HPMC in the prepared coats from 10% to 20% resulted in an increase in the release rate. However, further increase in HPMC concentration to constitute 30% caused a reduction in the release rate. Based on the drug release results, tablets coated with coat consisted of 80% guar gum and 20% HPMC were selected for in vivo evaluation. In vivo gamma scintigraphic study on human volunteers using technetium-99m-diethylenetriamine pentaacetic acid as a tracer was performed. The results showed that tablets remained intact in stomach and small intestine, however partial and complete release of the tracer occurred in the colon. In conclusion, guar gum in combination with HPMC would be successfully used as a carrier for drug delivery to the colon.

Considering the advantageous for the rectal administration of non-steroidal anti-inflammatory drugs, the objective of this study was to formulate and evaluate rectal mucoadhesive hydrogels loaded with diclofenac-sodium chitosan (DFS-CS) microspheres. Hydroxypropyl methylcellulose (HPMC; 5%, 6%, and 7% w/w) and Carbopol 934 (1% w/w) hydrogels containing DFS-CS microspheres equivalent to 1% w/w active drug were prepared. The physicochemical characterization revealed that all hydrogels had a suitable pH for rectal application (6.5–7.4). The consistency of HPMC hydrogels showed direct proportionality to the concentration of the gelling agent, while carbopol 934 gel showed its difficulty for rectal administration. Farrow’s constant for all hydrogels were greater than one indicating pseudoplastic flow. In vitro drug release from the mucoadhesive hydrogel formulations showed a controlled drug release pattern, reaching 34.6–39.7% after 6 h. The kinetic analysis of the release data revealed that zero-order was the prominent release mechanism. The mucoadhesion time of 7% w/w HPMC hydrogel was 330 min, allowing the loaded microspheres to be attached to the surface of rectal mucosa. Histopathological examination demonstrated the lowest irritant response to the hydrogel loaded with DFS-CS microspheres in response to other forms of the drug.

Gadolinium neutron capture therapy (Gd-NCT) is a promising approach to fight cancer. One key factor for the success of Gd-NCT is to deliver and maintain a sufficient amount of Gd inside tumors. A large amount of Gd can be readily introduced into tumors by direct intratumor injection. However, an innovative approach is needed to maintain the Gd in the tumors. We encapsulated a Gd compound into a liposome formulation and then dispersed the liposomes into a thermo-sensitive polymeric gel. In murine tumor models, we showed that this liposome-in-thermo-sensitive gel system significantly extended the retention of the Gd compound in tumors. This similar concept may be applied to prolong the retention of other cytotoxic chemicals in tumors, and thus, improve their anti-tumor efficacy.

An attractive approach to immunization is to apply DNA vaccine topically onto the skin. However, it is important to ensure that a strong immune response is induced without disrupting the skin stratum corneum. The hair follicles have been shown to be the major portal of entry for DNA applied onto the skin, and it has been reported that the transfection of hair follicle cells occurs mainly at the onset of a new growing stage of the hair cycle. Using an anthrax protective antigen (PA) protein-encoding plasmid in mice, we demonstrated that the anti-PA immune responses were significantly stronger when the hair follicles in the application area were induced into anagen-onset stage than when in telogen stage. The anti-PA antibodies enabled the immunized mice to survive a lethal dose of anthrax lethal toxin challenge. The enhanced immune responses can be partially attributed to the enhanced antigen gene expression and plasmid DNA uptake in the skin area wherein the hair follicles were induced into anagen-onset stage. Moreover, the moderate dermal inflammation associated with the anagen induction may also have contributed to the enhancement of the resultant immune response. This represents a novel approach to enhancing the immune response induced by a topically applied DNA vaccine.

Coaxing dead tumor cells to induce specific immune responses is an attractive tumor therapy. However, there continues to be a need for adjuvants that can promote the cross-presentation of the dead tumor cells to induce specific anti-tumor response. Viral dsRNA has multiple mechanisms to promote the cross-presentation of viral antigens in virus-infected cells. We propose to learn from viruses by generating dead tumor cells having synthetic dsRNA delivered inside them to allow the dsRNA to promote the cross-presentation of dead tumor cells.Using synthetic dsRNA, poly(I:C), and the TC-1 cervical cancer model, we evaluated the extent to which the poly(I:C) can promote the necrotic bodies of TC-1 cells to induce specific anti-tumor immune response. The poly(I:C) was either simply mixed with the dead TC-1 cells or pre-loaded inside them.Immunization of tumor-bearing mice with the necrotic bodies of tumor cells admixed with poly(I:C) significantly inhibited the tumor growth. More importantly, immunization with the necrotic bodies having poly(I:C) pre-loaded inside led to a significantly stronger anti-tumor response than when the necrotic bodies were simply admixed with the poly(I:C), apparently through a CD8(+) CTL response-mediated mechanism.These findings are expected to be clinically relevant for devising improved whole cell-based tumor vaccines.

One of the main challenges in Tamoxifen cancer therapy is achieving localized, efficient and sustained delivery without harming normal healthy organs. This study focused on evaluating Tamoxifen Citrate (TMC) niosomes for localized cancer therapy through in-vitro breast cancer cytotoxicity as well as in-vivo solid anti-tumor efficacy. Different niosomal formulae were prepared by film hydration technique and characterized for entrapment efficiency% (E. E), vesicle size, morphology, and in-vitro release. The cellular uptake and anti-cancer activity were also tested in-vitro using MCF-7 breast cancer cell line. Moreover, in-vivo anti-tumor efficacy was examined in Ehrlich carcinoma mice model through reporting solid tumor volume regression and tissue TMC distribution. The obtained niosomes prepared with Span 60: cholesterol (1: 1 molar ratio) showed a distinct nano-spherical shape with EE up to 92.3%± 2.3. Remarkably prolonged release of TMC following diffusion release behavior was detected. The optimized formula showed significantly enhanced cellular uptake (2.8 fold) and exhibited significantly greater cytotoxic activity with MCF-7 breast cancer cell line. In-vivo experiment showed enhanced tumor volume reduction of niosomal TMC when compared to free TMC. Based on these results, the prepared niosomes demonstrated to be promising as a nano-size delivery vehicle for localized and sustained TMC cancer therapy.

In a previous study, the enhancement effects on the transport of a steroidal permeant along the hairless mouse skin (HMS) stratum corneum (SC) lipoidal pathway were investigated for two homologous series of chemical enhancers: the 1‐alkyl‐2‐pyrrolidones and the 1‐alkyl‐2‐azacycloheptanones. The objective of the present study was to extend this investigation to a broader range of enhancers in order that generalizations with regard to the mechanistic aspects of enhancer function might be established. Specific questions to be addressed included: (a) what is the nature of the microenvironment of the enhancer site of action? (b) what is the extent of the equilibrium uptake of the enhancer from its E = 10 aqueous enhancer solution (the aqueous concentration for which the enhancer induces a tenfold transport enhancement) into the HMS SC intercellular lipid “phase”? and (c) are the microenvironment of the enhancer site of action and that for the equilibrium enhancer uptake at E = 10 relatively independent of the molecular characteristics of the enhancers (as suggested by the earlier study)? Enhancers selected for this study included: a wide range of polar head group size and polarity; n ‐alkyl group chain lengths from C 4 to C 12 ; and enhancers in which a double bond is substituted for a single bond in the hydrocarbon chain (3‐alkenols) from C 5 to C 9 . In addition to the main study, an ancillary set of experiments were to be conducted on the partitioning of a surrogate permeant (estradiol) into the intercellular lipid “phase” under E = 10 isoenhancement conditions to assess the extent to which the permeant partition coefficient may contribute to the permeation enhancement. The following were the principal findings of this research. First, there was very good correlation between the E = 10 isoenhancement aqueous enhancer concentrations and K octanol/water for all the studied enhancers. Second, the partitioning of the enhancer from the E = 10 aqueous enhancer solution into the HMS SC intercellular lipid “phase” was found to be relatively independent of the molecular characteristics for all studied enhancers, and the partition coefficients also correlated well with K octanol/water . These results may have the following meanings: both the microenvironment of the enhancer site of action and the SC intercellular lipid “phase” involved in the enhancer partitioning experiments are well mimicked by liquid n ‐octanol, and the “intrinsic” potencies (as assessed by the equilibrium enhancer concentration in the microenvironment at the site of action) of the enhancers are relatively independent of the molecular characteristics of the studied enhancers. Finally, the estradiol partitioning experiments suggest the permeant partitioning into the HMS SC intercellular lipid “phase” is enhanced around five‐ to seven‐fold when permeation is enhanced ten‐fold for most of the studied enhancers; therefore, the enhancement of the permeant partition coefficient rather than the permeant diffusion coefficient seems to be more important in permeation enhancement of the SC barrier lipoidal pathway. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1415–1430, 2004

The use of penetration enhancer adjuvants was emerged as a growing trend intransdermal drug delivery. These adjuvants may reduce the capacity for drug binding to skinand promote the permeation of bimolecules through the skin. The main objective of this studywas to evaluate the effect of polyvinylpyrrolidone (PVP) and hydroxypropyl–beta-cyclodextrin(HP- -CD) as well as certain chemical enhancers on solubility of unlabeled corticosterone(CS) and its transdermal permeation through skin. The results revealed that autoclaving CSwith PVP maintained supersaturated state through inhibition of crystal growth and in turnincreased its flux across hairless mouse skin. The data showed also that HP- -CD had no effecton CS permeation but could be used as solubilizing agent for highly lipophilic skin permeationenhancers octyl pyrrolidone (OP) and dodecyl pyrrolidone (DDP). It also prevented depletionof such lipophilic enhancers into skin, increased by this way the permeation enhancement ofthese adjuvants

A new generation anthrax vaccine is expected to target not only the anthrax protective antigen (PA) protein, but also other virulent factors of Bacillus anthracis. It is also expected to be amenable for rapid mass immunization of a large number of people. This study aimed to address these needs by designing a prototypic triantigen nasal anthrax vaccine candidate that contained a truncated PA (rPA63), the anthrax lethal factor (LF), and the capsular poly-gamma-D-glutamic acid (gammaDPGA) as the antigens and a synthetic double-stranded RNA (dsRNA), polyriboinosinic-polyribocytodylic acid (poly(I:C)) as the adjuvant. This study identified the optimal dose of nasal poly(I:C) in mice, demonstrated that nasal immunization of mice with the LF was capable of inducing functional anti-LF antibodies (Abs), and showed that nasal immunization of mice with the prototypic triantigen vaccine candidate induced strong immune responses against all three antigens. The immune responses protected macrophages against an anthrax lethal toxin challenge in vitro and enabled the immunized mice to survive a lethal dose of anthrax lethal toxin challenge in vivo. The anti-PGA Abs were shown to have complement-mediated bacteriolytic activity. After further optimization, this triantigen nasal vaccine candidate is expected to become one of the newer generation anthrax vaccines.

Literature reports reveal that the issue of whether cyclodextrins may act as skin permeation enhancers has not been resolved. Accordingly, in vitro skin transport studies were conducted to address this question. Corticosterone (3H-CS and/or non-radiolabeled CS) was chosen as the model permeant for transport experiments with hairless mouse skin (HMS) and with a synthetic cellulose membrane of 500 molecular weight cut off (MWCO), the latter to help establish baseline behavior. Hydroxypropyl-beta-cyclodextrin (HPbetaCD) was selected as the representative cyclodextrin. The CS/HPbetaCD complexation constant was determined both from solubility data (saturation conditions) in phosphate buffered saline (PBS), pH 7.4 and with data obtained from PBS/silicone polymer partitioning experiments, the latter experiments permitting the determination of the complexation constant at low CS concentrations. These results were used in the calculations of the free CS concentrations in the donor chamber of the transport experiments. The CS transport experiments were conducted at CS solubility saturation and under supersaturation (resulting from autoclaving at 121 degrees C) conditions as well at very low (tracer level) concentrations. The effect of polyvinylpyrrolidone as a solution additive was also evaluated. The following were the key outcomes of this study. Contrary to literature reports, there was no evidence that HPbetaCD is an enhancer for CS transport through HMS. The CS permeability coefficient values obtained with HMS in all of the experiments were found to be the same within experimental error when calculated on the basis of the free CS concentration as the driving force for permeation. The constancy of the permeability coefficient in the presence and absence of HPbetaCD is interpreted to mean that, in these experiments, HPbetaCD did not alter the barrier properties of HMS stratum corneum to any significant extent nor did it enhance CS transport in any other manner such as by a carrier mechanism involving the aqueous boundary layer or by a carrier mechanism within the stratum corneum.