Liposomal Gel Formulations Research Articles

Design, preparation, and evaluation of liposomal gel formulations for treatment of acne: in vitro and in vivo studies

The study highlights the significance of co-application of bioactive components into liposomal gel formulations and their comparison to azithromycin for treatment of Acne. A Design of Experiments (DoE) approach was utilized to obtain optimized liposomal formulation encapsulating curcumin, with size and zeta potential of ∼100 nm and ∼14 mV, respectively, characterized by DLS, HR-TEM, FESEM, and AFM. The curcumin liposomal dispersion depicted excellent stability over the period of 60 days, which was further converted in gel form using Carbopol. Pharmacokinetics of curcumin-loaded liposomal gel showed that Tmax for curcumin was achieved within 1 h of post application in both stratum corneum and skin, indicating quick penetration of nano-sized liposomes. Stratum corneum depicted Cmax of 688.3 ng/mL and AUC0-t of 5857.5 h × ng/mL, while the skin samples displayed Cmax of 203.3 ng/gm and AUC0-t of 2938.1 h × ng/gm. Lauric acid and azithromycin liposomal gel formulations were prepared as per the optimum parameters obtained by DoE. In antibacterial activity using agar diffusion assay, lauric acid gel formulation revealed ∼1.5 fold improved antibacterial effect than curcumin gel formulation. Interestingly, their co-application (1:1) exhibited significantly enhanced antibacterial effect against both macrolide-sensitive (1.81 versus 1.25 folds) and resistant strains of P. acnes (2.93 versus 1.22 folds) than their individual counterparts. The in vivo studies in rat ear model displayed a ∼2 fold reduction in comedones count and cytokines (TNF-α and IL-1β) on co-application with curcumin and lauric acid liposomal gel compared to placebo treated group.

Long-lasting Insulin Treatment Via a Single Subcutaneous Administration of Liposomes in Thermoreversible Pluronic® F127 Based Hydrogel.

Repeated administrations of insulin injection on daily basis evoke pain and numerous complications with adverse effects on the diabetic patients' life quality. Moreover, wearing insulin pump is also associated with several problems of diabetic ketoacidosis, catheter site infection, contact dermatitis and high cost. We have developed an in situ gel system, consisting of insulin-loaded liposomes dispersed within a thermoreversible gel (Pluronic® F127 gel), which increases the duration of insulin action for the treatment of diabetes. Vesicular phospholipid gel technique was used to encapsulate the insulin into liposomes. The resulting liposomal gel formulation had a longer drug-release period in vitro than a free insulin solution or liposomes and Pluronic® F127 gel individually. Furthermore, the addition of liposomes to the Pluronic® F127 gel improved the stability of the encapsulated insulin at a physiological temperature. In vivo study was performed to investigate the bioactivity and absorption of insulin released from the liposomal gel and other formulations. The liposomal gel released insulin into the bloodstream continuously for up to 7 days and significantly enhanced drug bioavailability compared to insulin released from liposomes or Pluronic® F127 gel individually. Blood glucose levels were reduced for up to 4 days. Histology data demonstrated excellent biocompatibility of the Pluronic® F127 gel-based delivery systems, with no observable inflammatory response in rat subcutaneous tissues. Obtained results show that the insulin-loaded liposomes dispersed within Pluronic® F127 gel can be used as a long-acting drug delivery system, and replacement for conventional insulin therapy.

Topical Loperamide-Encapsulated Liposomal Gel Increases the Severity of Inflammation and Accelerates Disease Progression in the Adjuvant-Induced Model of Experimental Rheumatoid Arthritis.

This study evaluates the prophylactic effect of the peripherally-selective mu-opioid receptor agonist, loperamide, administered topically in a liposomal gel formulation on pain, inflammation, and disease progression in the adjuvant-induced model of experimental rheumatoid arthritis in female Lewis rats. In a randomized, blinded and controlled animal trial, AIA rats were divided into six groups consisting of eleven rats per group based on the following treatments: loperamide liposomal gel, free loperamide gel, empty liposomal gel, diclofenac gel (Voltaren®), no treatment, and naive control. Topical formulations were applied daily for a maximum of 17 days—starting from day 0 at the same time as immunization. The time course of the effect of the treatments on antinocieption and inflammation was assessed using a paw pressure analgesiometer and plethysmometer, respectively. Arthritis progression was scored daily using an established scoring protocol. At the end of the study, hind paws were processed for histological analysis. Administration of loperamide liposomal gel daily across the duration of the study produced significant peripheral antinociception as expected; however, increased the severity of inflammation and accelerated arthritis progression. This was indicated by an increase in paw volume, behavioral and observational scoring, and histological analysis compared to the control groups. In particular, histology results showed an increase in pannus formation and synovial inflammation, as well as an upregulation of markers of inflammation and angiogenesis. These findings may have implications for the use of loperamide and other opioids in arthritis and potentially other chronic inflammatory diseases.

The ameliorated longevity and pharmacokinetics of valsartan released from a gel system of ultradeformable vesicles

Objective: The present study traces the development and characterization of the gel formulation of valsartan-loaded ultradeformable vesicles for management of hypertension. Materials and methods: The prepared gel formulation of ultradeformable vesicles was evaluated for in vitro skin permeation, release kinetics, skin irritation, pharmacokinetics, and stability. Results and discussion: The in vitro skin permeation study showed that the gel formulation of ultradeformable vesicles presented a flux value of 368.74 μg/cm2/h, in comparison to that of the traditional liposomal gel formulation, with an enhancement ratio of 26.91, through rat skin. The data for release kinetics showed that the release profile followed zero-order kinetics, and that the drug release mechanism was non-Fickian. The results of the skin irritation study demonstrated that the prepared formulation was safe, less irritant, and well-tolerated for transdermal delivery. The results of the pharmacokinetic study demonstrated that the AUC value of valsartan after transdermal administration was apparently increased. The formulation stored under a refrigerated condition showed greater stability, and results were found to be within the specification under storage conditions. Conclusion: It is evident from this study that the gel formulation of ultradeformable vesicles of valsartan is a promising delivery system for lipophilic drugs, and has reasonably good stability characteristics.

DEVELOPMENT AND CHARACTERIZATION OF PREDNISOLONE LIPOSOMAL GEL FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

The present objective for the study was to prepare prednisolone liposomal gel intended for topical application. Various liposome formulations were prepared using Vortexing Sonication technique using vacuum rotator evaporator by varying the lipid phase composition (lecithin/cholesterol). Liposome formulations were characterized for drug content, entrapment efficiency, surface morphology, surface charge, and stability studies. Topical liposomal gels were prepared by incorporation of liposo me dispersion into structured vehicl e carbopol (2 %). Alternatively, hydrogels containing prednisolone were prepared and their drug release properties were investigated. The percentage entrapment of drug was increased with increase in phospholipid composit ion in the range of 85 - 98 %. L iposomal gel showed prolonged release of prednisolone than the hydrogels. Results of all the studies suggested that Prednisolone liposomal gel formulation was therapeutically effective drug delivery system for treatment of Rhe umatoid Arthritis.

Development of an Effective Topical Liposomal Formulation for Localized Analgesia and Antiinflammatory Actions in the Complete Freund’s Adjuvant Rodent Model of Acute Inflammatory Pain

Background: Peripheral opioid receptor targeting has been well established as a novel target in clinical pain management for acute and chronic peripheral inflammatory pain. The physiochemical properties of the peripheral mu-opioid receptor agonist, loperamide HCl, limit the use of the free drug as an analgesic or anti-inflammatory agent, particularly for dermal delivery across intact skin. Objective: Our objective was to manufacture an effective topical formulation containing loperamide using liposomal delivery that would allow loperamide to produce analgesia and anti-inflammatory effects, by penetrating the epidermis to reach peripheral opioid receptors within the dermis of intact skin. Study Design: A randomized, double blind, controlled animal trial. Methods: Thirty-five adult male Wistar rats (200 – 250 g) were randomly divided into 5 groups: loperamide HCl-encapsulated liposomal gel, naloxone methiodide + loperamide HCl-encapsulated liposomal gel, free loperamide gel, empty liposomal gel, and 1% diclofenac gel (Voltaren®). Diclofenac gel was used as a positive control as it is clinically used as a topical analgesic and anti-inflammatory drug. Animals received an intraplantar injection of 150 µl Complete Freund’s Adjuvant (CFA) into the right hindpaw and experiments were performed 5 days post-CFA injection, which corresponded to the peak inflammatory response. All manufactured formulations were applied topically on both hind paws twice daily, whereas Voltaren gel was applied 3 times a day in accordance with the manufacturer’s instructions. The dose administered was 50 µl, which equated to 0.4 mg of loperamide HCl for the loperamide HCl treatment groups (low dose). Naloxone methiodide (1 mg/kg) was administered via intraplantar injection, 15 minutes prior to application of loperamide HCl-encapsulated liposomal gel to determine opioid receptor dependent activity. An investigator blinded to the treatment administered assessed time course of the antinociceptive and antiinflammatory effects using a paw pressure analgesiometer and plethysmometer, respectively. Results: Application of loperamide HCl in a liposomal gel formulation exerted analgesic and antiinflammatory effects exclusively in peripheral painful inflamed tissue. This formulation produced highly significant analgesic and anti-inflammatory effects over the 48-hour time course studied following topical administration in rats with CFA-induced inflammation of the paw. As expected, the diclofenac gel group showed significant antinociception over the duration of the study; however, this effect was lower in comparison to the loperamide HCl liposomal gel formulation. All other control groups showed no significant antinociceptive effects. In addition, all control groups (1% diclofenac gel, free loperamide gel, and empty liposomal gel) did not demonstrate a significant change in paw volume over 48 hours. Limitations: In vivo studies were performed in the well-established rodent model of acute inflammatory pain. We are currently studying this approach in chronic pain models known to have clinical activation of the peripheral immune-derived opioid response. Conclusions: The study demonstrates that topically applied loperamide encapsulated within liposomal systems has improved therapeutic efficacy over conventional formulations for the local treatment of acute peripheral inflammatory pain conditions where the skin has remained intact. Once in the inflamed peripheral tissue, loperamide provides analgesic and anti-inflammatory effects in a similar manner to peripheral endogenous opioids. This preparation optimises the retention of drug at the site where action is required. Key words: Pain, inflammation, opioids, loperamide, liposomes, topical drug delivery, peripheral opioid receptors

Liposomal gels for site-specific, sustained delivery of celecoxib: in vitro and in vivo evaluation.

The objective of this work was to evaluate liposome-containing gel formulations for the sustained, site-specific delivery of celecoxib (CXB). Liposomes composed of phosphadtidylcholine (and various amounts of cholesterol (Ch) were prepared using thin film hydration and characterized for encapsulation efficiency, vesicle size, and drug-excipient interaction using differential scanning calorimetry and Fourier-transform infrared spectroscopy. The selected liposome formulation was incorporated in different gel formulations: the Ch ratio affected the encapsulation efficiency of the drug, by increasing Ch ratio up until 1:1 the encapsulation efficiency increased. Further increasing the Ch ratio resulted in decreasing encapsulation efficiency. In vitro drug release and skin permeation studies showed sustained release and enhanced permeation compared with gel formulations containing free drug. In the rat paw edema test, the anti-inflammatory activity of the selected liposomal gel formulation was higher and more sustained compared with that of the nonliposomal gel formulation containing free drug. These results suggest that the liposome-containing gels are promising formulations for sustained, site-specific delivery of CXB.

Comparison of in vitro dialysis release methods of loperamide-encapsulated liposomal gel for topical drug delivery

BackgroundThe purpose of this study was to determine the most appropriate dialysis equilibrium method to assess liposomal gel formulations containing hydrophobic drugs, to give the most accurate indication of drug release.MethodsLoperamide hydrochloride-encapsulated liposomes, composed of L-α-phosphatidylcholine and cholesterol (molar ratio of 2:1), were prepared according to the method of dried lipid film hydration. The liposomes were incorporated into a carbopol gel (0.5%, weight/weight). The release of the drug from the nanoparticles was assessed using a number of variations of the dialysis technique, taking into account solubility parameters and formulation. Method 1 (below saturation point) and Method 2 (above saturation point) used a dilution method to evaluate how drug concentration and solubility affects the in vitro drug-release profile of loperamide hydrochloride, while Methods 3 (below saturation point) and 4 (above saturation point) evaluated how drug concentration and the gel base affect the release profile.ResultsIn Method 1, the liposomes showed a rapid release of just over 60% in the first 3 hours and then a slower, sustained release to just over 70% at 24 hours. Method 2 showed a gradual, sustained release profile with the liposomes with 55% release at 24 hours. In Method 3, the liposomes showed a rapid burst release of 98% at 2 hours. In Method 4, the liposomal gel had a rapid release of 60% within 3 hours and then a more gradual, sustained release with 86% release at 24 hours. The free drug suspension in Methods 2 and 4 showed a limited release across the dialysis membrane, in comparison to Methods 1 and 3, which showed a complete release in a timely manner.ConclusionThis study has demonstrated that the actual method used for equilibrium dialysis plays a significant role in determining the true characteristics of a topical nanoformulation, with Method 3 providing the most accurate indication of the release of a hydrophobic drug from a topical liposomal formulation.

Transdermal delivery of butamben using elastic and conventional liposomes

Gel formulations containing the local anesthetic butamben (BTB) encapsulated in either conventional (BTBLUV) or elastic (BTBLUV-EL) liposomes were prepared and characterized, and then evaluated in terms of their skin permeability. Parameters measured included vesicle size and surface charge, BTB fluorescence anisotropy, encapsulation efficiency, partition coefficient and liposomal membrane organization. Encapsulation efficiencies and membrane/water partition coefficients were determined using a phase separation. The partition coefficients of the elastic and conventional formulations were 2025 ± 234 and 1136 ± 241, respectively. The sizes of the elastic and conventional liposomes did not change significantly (p > 0.05) following incorporation of the anesthetic. As expected, the elastic liposomes presented order parameters that were lower than those of the conventional liposomes, as determined by electron paramagnetic resonance with a 5-stearic acid nitroxide probe incorporated into the bilayer. After 8 h, the fluxes into the receiving solution (µg/cm2/h) were 6.95 ± 1.60 (10% BTB), 23.17 ± 6.09 (10% BTBLUV) and 29.93 ± 6.54 (10% BTBLUV-EL). The corresponding time lags (h) were 1.90 ± 0.48, 1.23 ± 0.28 and 1.57 ± 0.38, respectively. The permeability coefficients (10−3 cm/h) were 1.02 ± 0.23, 2.96 ± 0.77 and 4.14 ± 0.9, for 10% BTB, 10% BTBLUV and 10% BTBLUV-EL, respectively. The results demonstrate that anesthetic access through the skin can be considerably enhanced using liposomal gel formulations, compared to plain gel formulations.

Preparation and Characterization of Liposomes Containing Essential Oil of Eucalyptus camaldulensis Leaf

The increased incidence of fungal resistance has necessitated the need to search for new antifungal agents. The main objectives of the present study were to investigate the effectiveness of the essential oil of Eucalyptus camaldulensis on dermatophytes growth and to formulate and characterize a liposomal gel loaded with the essential oil. The essential oil extracted from the leaves of E. camaldulensis was analyzed by GC-MS. The antifungal activity of this essential oil was determined against Microsporum canis, M. gypseum, Trichophyton rubrum and T. verrucosum, using the well diffusion method. Liposomes were prepared by the freeze-thaw method and evaluation of size distribution was performed using a particle size analyzer. The liposomal gel was prepared using 'hydroxethyl cellulose (HEC) as the gelling agent. The rheologic characteristics were determined by a Brookfield viscometer. The results showed that the minimum inhibitory volume of the essential oil was 0.125 ml and 95 ± 0.57% of the essential oil was successfully entrapped in the liposomes. The main constituents of the essential oil detected by GC-MS were; phenol, 1, 8 cineole, limonene, alcohol, pinene and terpinen. Results of particle size determination showed a wide range from 40.5 to 298 nm for the different formulations. No significant thixotropy was observed in the rheogram of the formulated liposomal gel. Liposomal gel formulation of the essential oil may lead to improved antifungal activity.

Preparation and Characterization of Liposomes Containing Essential Oil of Eucalyptus camaldulensis Leaf

Background: The increased incidence of fungal resistance has necessitated the need to search for new antifungal agents. Objective: The main objectives of the present study were to investigate the effectiveness of the essential oil of Eucalyptus camaldulensis on dermatophytes growth and to formulate and characterize a liposomal gel loaded with the essential oil. Materials and Methods: The essential oil extracted from the leaves of E. camaldulensis was analyzed by GC-MS. The antifungal activity of this essential oil was determined against Microsporum canis, M. gypseum, Trichophyton rubrum and T. verrucosum, using the well diffusion method. Liposomes were prepared by the freeze-thaw method and evaluation of size distribution was performed using a particle size analyzer. The liposomal gel was prepared using ‘hydroxethyl cellulose (HEC) as the gelling agent. The rheologic characteristics were determined by a Brookfield viscometer. Results: The results showed that the minimum inhibitory volume of the essential oil was 0.125 ml and 95 ± 0.57% of the essential oil was successfully entrapped in the liposomes. The main constituents of the essential oil detected by GC-MS were; phenol, 1, 8 cineole, limonene, alcohol, pinene and terpinen. Results of particle size determination showed a wide range from 40.5 to 298 nm for the different formulations. No significant thixotropy was observed in the rheogram of the formulated liposomal gel. Conclusion: Liposomal gel formulation of the essential oil may lead to improved antifungal activity.

Development of liposome gel based formulations for intravaginal delivery of the recombinant HIV-1 envelope protein CN54gp140

Mucosally-administered vaccine strategies are widely investigated as a promising means of preventing HIV infection. This study describes the development of liposomal gel formulations, and novel lyophilised variants, comprising HIV-1 envelope glycoprotein, CN54gp140, encapsulated within neutral, positively charged or negatively charged liposomes. The CN54gp140 liposomes were evaluated for mean vesicle diameter, polydispersity, morphology, zeta potential and antigen encapsulation efficiency before being incorporated into hydroxyethyl cellulose (HEC) aqueous gel and subsequently lyophilised to produce a rod-shaped solid dosage form for practical vaginal application. The lyophilised liposome–HEC rods were evaluated for moisture content and redispersibility in simulated vaginal fluid. Since these rods are designed to revert to gel form following intravaginal application, mucoadhesive, mechanical (compressibility and hardness) and rheological properties of the reformed gels were evaluated. The liposomes exhibited good encapsulation efficiency and the gels demonstrated suitable mucoadhesive strength. The freeze-dried liposome–HEC formulations represent a novel formulation strategy that could offer potential as stable and practical dosage form.

Chitosan-reduced gold nanoparticles: a novel carrier for the preparation of spray-dried liposomes for topical delivery

Exposure of skin to various chemical and physical agents results in excessive stress to the outermost cell layer of the skin, causing different degenerative effects that can be minimized by using antioxidant formulations. The major challenge, in this regard, is to develop a formulation, which can prevent photodegradation of the actives, thus allowing a significant amount to be deposited at the site. In recent decades, liposomal formulations have been extensively employed to overcome the barrier properties of the skin and photodegradation of actives. In the present study, chitosan-reduced gold nanoparticles were investigated for its potential as a carrier to prepare liposomes by a spray-drying method. Liposomes so obtained were characterized for phospholipid recovery, diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy, particle size, zeta potential, encapsulation efficiency, and deposition of drug and gold nanoparticles in the rat skin. Further, a liposomal gel formulation was prepared using Carbopol® 980 NF (Noveon Systems, Kochi, India) and evaluated for drug deposition in the skin. Antioxidant activity of vitamin C encapsulated in gold liposomes was determined on a human leukemia (HL-60) cell line. The use of gold nanoparticles as a carrier showed improved phospholipid recovery and thus overcomes the liposome scalability problem. DRIFT spectra confirmed the presence of phospholipid in the formulation. Liposomal gel showed improved drug deposition, as compared to control and marketed preparations. A more interesting contribution of the chitosan-reduced gold nanoparticles was an enhanced antioxidant activity seen in case of the vitamin C–loaded gold liposomal formulation. Liposomal formulation was found to be stable for 3 months at 30°C and 65% relative humidity.

Development of Topical Diclofenac Sodium Liposomal Gel for Better Antiinflammatory Activity

The objective of this study was to develop a diclofenac liposomal gel intended for better anti-inflammatory activity compared to a normal gel after topical administration. Spherical multilamellar vesicular liposomes (MLVs) consisting of soya lecithin, cholesterol and diclofenac were prepared via thin film hydration methodology. Small unilamellar vesicles (SUVs) were then prepared out of MLVs. Entrapment efficiency, the drug associated with SUVs was subsequently determined. Liposomal gel formulations were then prepared by incorporation of SUVs into carbopol 934 gel previously prepared. The formulations were then characterized for in vitro drug release, ex vivo permeation studies, drug-lipid compatibility and rheological behaviour. Vesicle size/Zeta potential of the liposomes containing in one selected formulation were determined. Pharmacodynamics was also determined for selected diclofenac liposomal gel. Diclofenac liposomal gel formulation prepared showed more sustained and prolonged anti-inflammatory effect compared with diclofenac gel. Taken together, the results indicate that the diclofenac liposomal gel is better than the regular gel without liposomes. Drug-lipid compatibility studies indicated no interaction with drug and the polymer.

Enhancement of transdermal delivery of phenylbutazone from liposomal gel formulations through deer skin

Phenylbutazone (PBZ) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain and arthritis. Topical and transdermal administration of PBZ would be beneficial in large animals in terms of minimizing gastro-intestinal ulcerations and other side effects, easy administration to legs and joints and minimizing the dose to reduce systemic toxicity of the drug. A topical liposomal preparation with different concentrations of a mono-substituted alkyl amide (MSA) and PBZ was formulated. The formulations were evaluated by in vitro skin-permeation kinetics through deer skin using Franz diffusion cells. By increasing drug loading from 1% to 5% w/w, the steady-state flux (microg/cm(2)/h) of PBZ was increased twofold (P < 0.001). Similarly, by increasing the MSA concentration from 0% to 4%, the steady-state flux (microg/cm(2)/h) of PBZ was increased twofold (P < 0.001). Overall, by increasing the drug load and the use of an appropriate amount of the penetration enhancer, the steady-state flux of PBZ through skin was increased fourfold (P < 0.001). MSA at both 2% and 4% w/w concentrations significantly increased the skin levels of PBZ as compared with control (P < 0.05). In conclusion, MSA served as an effective skin-penetration enhancer in the liposomal gel of PBZ for deer.

In vivo Skin Deposition and Photoprotection Effect of Genistein in Liposomal Gel Formulations

To enhance the skin delivery of genistein (GT), a soybean isoflavone having anti oxidative activity, comparative formulation studies including liposomes were carried out. GT-loaded conventional and elastic liposomal gel showed the enhanced skin deposition and photoprotection effect as well, in comparison to GT suspension. Elastic liposomes composed of soybean phosphatidylcholine and sodium deoxycholate (85:15, w/w%) were superior to conventional liposomes and were of characteristics as follows: about 130 nm in size; 85% encapsulation efficiency of GT; 5.8% skin deposition of applied dose; 40% inhibition effect on UVB-induced production. Photoprotection effect was closely related to skin deposition of GT. In conclusion, it is possible to suggest that elastic liposomes could be a promising nanocarrier system for efficient skin delivery.

LIPOSOMAL GEL OF DICLOFENAC SODIUM AS TOPICAL DELIVERY SYSTEM

This study the preparation of diclofenac sodium in lecithin vesicles and loading in pluronic F-127 gel, the effect of sodium cholate on the diffusion of the drug through rat skin and the antiinflammatory activity of the liposomal gel formulations. Lecithin vesicles were prepared in the presence or absence of sodium cholate by the dry film method and sonication. The size of liposomal vesicles ranged from 100-700 nm and the encapsulation efficiency of the diclofenac sodium was between 60-80%. The lecithin vesicles were loaded in pluronic F-127 gel. The highest cumulative of drug diffusion through rat skin was 19.31± 1.50 (µg/cm2) for lecithin vesicles in the presence of sodium cholate (F4). Also the highest cumulative of drug diffusion through rat skin was 12.20± 0.50 (µg/cm2) for liposomal gel (F8). The antiinflammatory activity of the liposomal gel formulations was studied on carrageenan induced paw edema in rats. The results show that, F8 and F6 show superior anti-inflammatory activity in comparison with the other gel formulations. From the results, lecithin vesicles and liposomal gel of diclofenac sodium appear to be advantagesous for topical delivery of the drug.

Optimum modality for photodynamic therapy of tumors: gels containing liposomes with hydrophobic photosensitizers

AbstractPhotodynamic therapy (PDT) has entered an era of clinical acceptance; however, for its wider use, including drug formulations for topical applications, it must have a rapid effect and be free of skin‐photosensitization effects. Preclinical studies of two prototype formulations exhibiting successful therapeutic rates based on translucent gels containing liposomes with hydrophobic photosensitizers are presented. Experimental PDT of human tumors implanted in nude mice with liposomal gels containing meso‐tetrakisphenylporphyrin (TPP) or hydroxy‐aluminum phthalocyanine (PC) caused significant dystrophy of human basal cell carcinoma, amelanotic melanoma, breast carcinoma, and colorectal carcinoma. Whereas the drug‐to‐light time interval for TPP was 12 h, much less than that of most commercially available approved photosensitizers, 10 min was sufficient to disintegrate the effects of the PC liposomal gel. Liposomes containing hydrophobic photosensitizers were prepared either by extrusion through 100‐nm filters or using a microfluidizer. Histology of tumors in remission showed existence of overall necrosis and the presence of only small islets of tumorous cells in incomplete remission. Fibrinoid necrosis of the tumors was a visible sign of the therapeutic effect. TPP and PC from the gel were distributed by circulation to the organs and tissues in a different and more favorable pattern than by intravenous injection. We conclude that hydrophobic photosensitizers are preferable and more efficient for PDT (Ježek et al., Int J Cancer 103:693–702, 2003) and their liposomal gel formulations are predicted to be optimum preparations enabling wide ranging use of topical PDT for numerous cancer indications, initially for nonmelanoma skin cancer. Drug Dev Res 68:235–252, 2007 © 2007 Wiley‐Liss, Inc.

Fluorescence Monitoring of a Topically Applied Liposomal Temoporfin Formulation and Photodynamic Therapy of Nonpigmented Skin Malignancies

Meso-tetra(hydroxyphenyl)chlorin (mTHPC) (INN: Temoporfin) is a potent photodynamically active substance in clinical use today. Usually, the substance is given systemically and a known drawback with this administration route is a prolonged skin light sensitization. For the first time to our knowledge, a liposomal Temoporfin gel formulation for topical application was studied in connection with photodynamic therapy (PDT) of nonpigmented skin malignancies in humans. Intervals of 4 hr between drug administration and light irradiation were used. Sensitizer distribution within tumor and surrounding normal skin was investigated by means of point monitoring and imaging fluorescence spectroscopy before, during, and after PDT, showing high tumor selectivity. Furthermore, the bleaching of Temoporfin was studied during the PDT procedure by monitoring the fluorescence following excitation by using a therapeutic light. A 30-35% light-induced photometabolization was shown. No pain occurred during or after treatment. It was also observed that the treated area did not show any swollen tissue or reddening, as is often seen in PDT using topical delta-aminolevulinic acid. On controlling the patients one week after treatment, healing progress was observed in several patients and no complications were registered.

Efficacy of topical griseofulvin in treatment of tinea corporis

Tinea infections are among the most common dermatological conditions throughout the world. Griseofulvin is a classical oral fungistatic antibiotic, active against Epidermophyton floccosum, Trichophyton and Microsporum species, the causative fungi of tinea corporis. To evaluate the efficacy of topical griseofulvin in the treatment of tinea circinata using three different vehicles for drug delivery. Sixteen patients with tinea circinata were instructed to apply either griseofulvin gel form in group A or a similar placebo gel for control group; a niosomal gel formulation of griseofulvin for group B or; a liposomal gel formulation of griseofulvin for group C. Patients were evaluated both clinically and mycologically after 3 weeks. Marked improvement was seen for groups A, B and C both clinically and mycologically while no improvement was observed in the placebo group. Mild and transient irritation was reported in four patients. Our results show that topical griseofulvin preparations may be effective and safe in treating tinea circinata and that further large-scale studies may establish the high efficacy of the niosomal gel formulation.