5-Fluorouracil shell-enriched solid lipid nanoparticles (SLN) for effective skin carcinoma treatment

Context: The effective treatment of skin carcinoma is warranted for targeting the chemotherapeutic agents into tumor cells and avoiding unwanted systemic absorption.

Objective: This work was dedicated to the purpose of engineering highly penetrating shell-enriched nanoparticles that were loaded with a hydrophilic chemotherapeutic agent, 5-fluorouracil (5-FU).

Methods: Varying ratios of lecithin and poloxamer188 were used to produce shell-enriched nanoparticles by enabling the formation of reversed micelles within this region of the SLN. The localization of 5-FU within the shell region of the SLN, was confirmed using 5-FU nanogold particles as a tracer. SLN were introduced within sodium carboxy methylcellulose hydrogel, and then applied onto the skin of mice-bearing Ehrlich’s ascites carcinoma. The mice were treated with the gel twice daily for 6 weeks.

Results: The transmission electron microscope (TEM) revealed the formation of uniform nanoparticles, which captured reversed micelles within their shell region. The SLNs’ had particle size that ranged from 137?±?5.5?nm to 800?±?53.6, zeta potential of ?19.70?±?0.40?mV and entrapment efficiency of 47.92?±?2.34%. The diffusion of the drug-loaded SLN (269.37?±?10.92?μg/cm²) was doubled when compared with the free drug (122?±?3.09?μg/cm²) when both diffused through a hydrophobic membrane. SLN-treated mice exhibited reduced inflammatory reactions, with reduced degrees of keratosis, in addition to reduced symptoms of angiogenesis compared to 5-FU-treated mice.

Conclusion: SLN possesses the capacity to be manipulated to entrap and release hydrophilic antitumor drugs with ease.     

Optimization and evaluation of pluronic lecithin organogels as a transdermal delivery vehicle for sinomenine

The purpose of the present study was to prepare and optimize sinomenine (SIN) pluronic lecithin organogels system (PLO), and to evaluate the permeability of the optimized PLO in vitro and in vivo. Box–Behnken design was used to optimize the PLO and the optimized formulation was pluronic F127 of 19.61%, lecithin of 3.60% and SIN of 1.27%. The formulation was evaluated its skin permeation and drug deposition both in vitro and in vivo compared with gel. Permeation and deposition studies of PLO were carried out with Franz diffusion cells in vitro and with microdialysis in vivo. In vitro studies, permeation rate (J_ss) of SIN from PLO was 146.55?±?2.93?μg/cm²/h, significantly higher than that of gel (120.39?μg/cm²/h) and the amount of SIN deposited in skin from the PLO was 10.08?±?0.86?μg/cm², significantly larger than that from gel (6.01?±?0.04?μg/cm²). In vivo skin microdialysis studies showed that the maximum concentration (C_max) of SIN from PLO in “permeation study” and “drug-deposition study” were 150.27?±?20.85?μg/ml and 67.95?μg/ml, respectively, both significantly higher than that of SIN from gel (29.66 and 6.73?μg/ml). The results recommend that PLO can be used as an advantageous transdermal delivery vehicle to enhance the permeation and skin deposition of SIN.     

Elastic Liposomal Formulation for Sustained Delivery of Colchicine: In Vitro Characterization and In Vivo Evaluation of Anti-gout Activity

Colchicine, an alkaloid found in extracts of the plants Colchicum autumnale and Gloriosa superb, is effective in the treatment of acute gout and dermatological conditions like leuko-cytoclastic vasculitis, psoriasis, and Sweet’s syndrome. Oral administration of colchicine is associated with gastrointestinal side effects and its accumulation in the body leads to bone marrow suppression. In the present study, an attempt has been made for development and in vitro and in vivo evaluation of elastic liposomal formulation for topical delivery of colchicine. The in vitro skin permeation study across rat skin found transdermal flux for different elastic liposomal formulations to range between 32.8?±?1.2 and 44.4?±?1.9 μg h^?1 cm^?2, which was approximately seven to 11 times higher than obtained using drug solution (4.3?±?0.6 μg h^?1 cm^?2). The results of skin deposition study showed that elastic liposomal formulation provide 12.5-fold higher skin deposition as compared to drug solution of colchicine. Confocal laser scanning microscopy also revealed better accumulation and deeper penetration (up to 200 μm) of elastic liposomes than drug solution (up to 12 μm). The biological evaluation of various vesicular formulations and drug solution was carried out using monosodium urate-induced air pouch model. The results of anti-gout activity in rats showed better and sustained biological effects in 24 h measured in terms of exudate volume (63.1?±?5.7% and 9.6?±?0.5% reduction with elastic liposomes and drug solution, respectively), reduction in leukocyte count (74.2?±?6.0% and 4.1?±?0.3% reduction with elastic liposomes and drug solution, respectively), decrease in inflammatory cells accumulation, and collagen deposition with elastic liposomal formulation than drug solution. Hence, the present study reveals that elastic liposomal formulation of colchicine possesses greater potential to enhance skin accumulation, prolong drug release, and improve the site-specificity of colchicine.     

Controlled delivery of ropinirole hydrochloride through skin using modulated iontophoresis and microneedles

Abstract

The objective of this study was to investigate the effect of modulated current application using iontophoresis- and microneedle-mediated delivery on transdermal permeation of ropinirole hydrochloride. AdminPatch® microneedles and microchannels formed by them were characterized by scanning electron microscopy, dye staining and confocal microscopy. In vitro permeation studies were carried out using Franz diffusion cells, and skin extraction was used to quantify drug in underlying skin. Effect of microneedle pore density and ions in donor formulation was studied. Active enhancement techniques, continuous iontophoresis (74.13?±?2.20?µg/cm²) and microneedles (66.97?±?10.39?µg/cm²), significantly increased the permeation of drug with respect to passive delivery (8.25?±?2.41?µg/cm²). Modulated iontophoresis could control the amount of drug delivered at a given time point with the highest flux being 5.12?±?1.70?µg/cm²/h (5–7?h) and 5.99?±?0.81?µg/cm²/h (20–22?h). Combination of modulated iontophoresis and microneedles (46.50?±?6.46?µg/cm²) showed significantly higher delivery of ropinirole hydrochloride compared to modulated iontophoresis alone (84.91?±?9.21?µg/cm²). Modulated iontophoresis can help in maintaining precise control over ropinirole hydrochloride delivery for dose titration in Parkinson’s disease therapy and deliver therapeutic amounts over a suitable patch area and time.     

Influence of sonophoresis and chemical penetration enhancers on percutaneous transport of penbutolol sulfate

The effect of ultrasound and chemical penetration enhancers on transcutaneous flux of penbutolol sulfate across split-thickness porcine skin was investigated. Penbutolol sulfate is a potent, noncardioselective beta-blocker, which is used for the management of hypertension. The drug is one of the most lipid soluble of the β-adrenoceptor antagonists used clinically. It has an n-octanol/pH 7.4 buffer partition coefficient of 179 compared to a value of 22 for propranolol. The amount of penbutolol sulfate transported across the skin is low. In this project, we studied the effect of sonophoresis and chemical penetration enhancers on transdermal delivery of penbutolol sulfate. Low-frequency sonophoresis at a frequency of 20?kHz increased transcutaneous flux of penbutolol sulfate by 3.5-fold (27.37?±?μg?cm^?2?h^?1) compared to passive delivery (7.82?±?1.72?μg?cm^?2?h^?1). We also investigated the effect of 50% ethanol, 1% limonene and 2% isopropyl myristate (IPM) on transcutaneous permeation of penbutolol sulfate. IPM, ethanol and limonene at the concentration of 1%, 50% and 2%, respectively, increased the steady-state flux values of penbutolol sulfate 2.2- (17.07?±?3.24?μg?cm^?2?h^?1), 2.6?- (19.40?±?6.40?μg?cm^?2?h^?1) and 3.4-times (26.38?±?5.01?μg?cm^?2?h^?1) compared to passive delivery (7.76?±?2.9?μg?cm^?2?h^?1). The results demonstrate that although there were slight increases in flux values, ultrasound, ethanol, limonene and IPM did not significantly enhance the transdermal delivery of penbutolol sulfate. Future studies will examine ways of optimizing sonophoretic and chemical enhancer parameters to achieve flux enhancement.     

Ethosomes-based topical delivery system of antihistaminic drug for treatment of skin allergies

Abstract

Cetirizine is indicated for the treatment of allergic conditions such as insect bites and stings, atopic and contact dermatitis, eczema, urticaria. This investigation deals with development of a novel ethosome-based topical formulation of cetirizine dihydrochloride for effective delivery. The optimised formulation consisting of drug, phospholipon 90 G? and ethanol was characterised for drug content, entrapment efficiency, pH, vesicular size, spreadability and rheological behaviour. The ex vivo permeation studies through mice skin showed highest permeation flux (16.300?±?0.300?µg/h/cm²) and skin retention (20.686?±?0.517?µg/cm²) for cetirizine-loaded ethosomal vesicles as compared to conventional formulations. The in vivo pharmacodynamic evaluation of optimised formulation was assessed against oxazolone-induced atopic dermatitis (AD) in mice. The parameters evaluated were reduction in scratching score, erythema score, skin hyperplasia and dermal eosinophil count. Our results suggest that ethosomes are effective carriers for dermal delivery of antihistaminic drug, cetirizine, for the treatment of AD.     

RETRACTED ARTICLE: Preparation and characterization of novel lipid nanocapsules of ropivacaine for transdermal delivery

Abstract

Ropivacaine, a novel long-acting local anesthetic, has been proved to own superior advantage. However, the application form used in clinic, ropivacaine hydrochloride (Naropin® Injection), which should be administed intravenously, is causing poor patient convenience. The purpose of this study was to formulate ropivacaine (RPV) in lipid nanocapsules (LNCs) and character the potential of LNCs in delivering RPV transdermally to exploit novel external preparation. The RPV-LNCs were successfully prepared by phase inversion technique and the formulation was characterized in terms of size, zeta potential, ex vivo permeation study, and pharmacodynamics. The prepared RPV-LNCs displayed a typical core-shell structure with a narrow size distribution of 62.1?±?1.7?nm and drug loading of 1.35?±?0.20%. The results of differential scanning calorimetry (DSC) analysis and X-ray diffraction showed that RPV was in amorphous crystalline state when encapsulated into LNCs. Furthermore, the results of ex vivo permeation study displayed that RPV-LNCs had an improved permeability (349.0?±?11.5?μg?cm^?2 versus 161.0?±?1.3?μg?cm^?2) compared with free RPV. The results of histopathology study showed that interaction between LNCs and skin could break the close conjugation of corneocyte layers. In the mice writhing test, RPV-LNCs exhibited obvious analgesic effect by both prolonging pain latency and reducing the writhing response with an inhibition rate of 91.3% compared to the control group. In conclusion, RPV-LNCs could be a promising delivery system to encapsulate RPV and deliver RPV for transdermal administration.     

Effect of neat and binary vehicle systems on the solubility and cutaneous delivery of piperine

Vitiligo is a skin disease characterized by depigmentation disorders due to lack of melanin production. Piperine, an alkaloid extracted from black piper, is active in melanocytes proliferation. To achieve this, the drug has to reach the melanocytes which exist in the deep layer of the epidermis. Higher drug concentration can be obtained after application of optimized formulation to skin. Accordingly, the aim of this work is to investigate the effect of vehicles on skin penetration of piperine as the first step in development of optimized formulation. The tested vehicles include ethanol (Eth), propylene glycol (PG), polyethylene glycol 400 (PEG), and oleic acid (OA) and their combinations. Water was used as the control and skin permeation was monitored using rabbit ear model skin. The highest piperine solubility (48.6?mg/ml) and flux (40.8?μg/cm²?h) was achieved by Eth and the lowest piperine flux (1.17?μg/cm²?h) was reported for PEG. PG and OA showed piperine flux values comparable to that of the control. Among different combination systems, Eth-OA (75:25) binary system had the highest piperine flux (59.3?μg/cm²?h) followed by Eth-OA (50:50) (32.3?μg/cm²?h) and PG-OA (90:10) (22.7?μg/cm²?h). The study thus introduced a vehicle system as the first step in the development of topical formulation of piperine.     

Fabrication and evaluation of lipid nanoparticulates for ocular delivery of a COX-2 inhibitor

Context: The unique physiological limitations of the eye have been assigned as reason of low bioavailability by conventional drug delivery systems. There is need of such drug carriers, which ensure improved bioavailability as well as patient compliance upon instillation into the eye.

Objective: The present investigation deals with development of solid lipid nanoparticles (SLNs) containing celecoxib (CXB) for treatment of ophthalmic inflammations.

Materials and methods: The SLNs were formulated by melt-emulsion sonication and low temperature-solidification process and evaluated for particle size, surface morphology, physicochemical properties, percentage drug incorporation efficiency, in vitro drug release, in vitro trans-corneal permeation, in vivo efficacy in ocular inflammation, stability study and gamma scintigraphy study to assess the residence of solid lipid nanoparticles over ocular surfaces.

Results: The SLNs were spherical and the optimized formulation had particle size of 198.77?±?7.5?nm, which is quite suitable for ocular applications. The maximum entrapment efficiency of 92.46?±?0.07% was achieved for formulation SLN 20. The permeation across the cornea was also significantly better than aqueous suspension (8.21?±?0.67 versus 4.61?±?0.71) at p?<?0.05.

Discussion and conclusion: The SLN formulations demonstrated improved performance of entrapped CXB while mitigating the key parameters of ocular inflammation in rabbits. The particulate formulations have exhibited prolonged retention over ocular surfaces as evident from results of gamma scintigraphy using ^99mTc labeled SLNs.     

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 J_SS 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.     

Hyperbranched dendritic nano-carriers for topical delivery of dithranol

Abstract

The purpose of the current investigation was to explore the potential of polypropylene imine (PPI) dendrimers to deliver dithranol (DIT) topically and to evaluate its encapsulation, permeation and skin irritation potential. PPI (5.0 generation, 5.0?G) dendrimers and DIT-loaded PPI (DIT–PPI) were prepared and characterized by spectroscopy and transmission electron microscopy. DIT encapsulation, in vitro skin permeation study, skin irritation studies, fluorescent studies and tape stripping studies were performed. Loading of DIT was found to be pH dependent with maximum encapsulation at acidic pH (1.0?±?0.02, 17.2?±?0.56 and 57.1?±?1.32% at 7.4, 5.5 and 1.2 pH, respectively). DIT–PPI showed significantly enhanced permeation rate constant and lesser skin irritation (11.61?±?1.80?μg/cm²/h and 1.0, respectively) when compared with the plain DIT solution (2.72?±?0.31?μg/cm²/h and 2.3, respectively). Skin separation studies and confocal laser scanning microscope images showed that the dye-loaded dendrimers exhibits deposition of dye in pilosebaceous compartment. These studies demonstrate that PPI can be exploited to improve the topical bioavailability of the molecules in a controlled pattern. The enhanced accumulation of DIT via dendrimer carrier within the skin might help optimize targeting of this drug to the epidermal and dermal sites, thus creating new opportunities for well-controlled, modern topical application of DIT for the treatment of psoriasis.     

Potent enhancement of transdermal absorption and stability of human tyrosinase plasmid (pAH7/Tyr) by Tat peptide and an entrapment in elastic cationic niosomes

Abstract

Enhancement of transdermal absorption through rat skin and stability of the human tyrosinase plasmid (P) using Tat (T) and an entrapment in elastic cationic niosomes (E) were described. E (Tween61:cholesterol:DDAB at 1:1:0.5 molar ratio) were prepared by the freeze-dried empty liposomes (FDELs) method using 25% ethanol. TP was prepared by a simple mixing method. TPE was prepared by loading T and P in E at the T:P:E ratio of 0.5:1:160 w/w/w. For gel formulations, P, TP, PE and TPE were incorporated into Carbopol 980 gel (30?µg of plasmid per 1?g of gel). For the transdermal absorption studies, the highest cumulative amounts and fluxes of the plasmid in viable epidermis and dermis (VED) were observed from the TPE of 0.31?±?0.04?µg/cm² and 1.86?±?0.24?µg/cm²/h (TPE solution); and 4.29?±?0.40?µg/cm² and 25.73?±?2.40?µg/cm²/h (TPE gel), respectively. Only plasmid from the PE and TPE could be found in the receiving solution with the cumulative amounts and fluxes at 6?h of 0.07?±?0.01?µg/cm² and 0.40?±?0.08?µg/cm²/h (PE solution); 0.10?±?0.01?µg/cm² and 0.60?±?0.06?µg/cm²/h (TPE solution); 0.88?±?0.03?µg/cm² and 5.30?±?0.15?µg/cm²/h (PE gel); and 1.02?±?0.05?µg/cm² and 6.13?±?0.28?µg/cm²/h (TPE gel), respectively. In stability studies, the plasmid still remained at 4?±?2?°C and 25?±?2?°C of about 48.00–65.20% and 27.40–51.10% (solution); and 12.34–38.31% and 8.63–36.10% (gel), respectively, whereas at 45?±?2?°C, almost all the plasmid was degraded. These studies indicated the high potential application of Tat and an entrapment in elastic cationic niosomes for the development of transdermal gene delivery system.     

Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers: in vitro and in vivo studies

A bilayered mucoadhesive buccal film containing a combination of ornidazole (OD) and dexamethasone sodium phosphate (DEX) was prepared using solvent casting to treat oral ulcers. Films were systematically evaluated in vitro to obtain the optimum formulation. The therapeutic effects of these films were investigated in the rabbit oral ulcer model and the in vivo release of OD and DEX in the human oral cavity was also evaluated. The backing layer contained ethyl cellulose and an optimal mucoadhesive layer containing both OD and DEX was produced. Films from the optimum formulation were 0.427?±?0.015?mm thick, weighed 55.89?±?0.79?mg, and had a surface pH of 6.34?±?0.01. The drug content of the optimum formulation approximated the theoretical value with good uniformity (2.959?±?0.106?mg/cm² for OD and 0.877?±?0.031?mg/cm² for DEX). The formulation showed favorable swelling characteristics and both drugs were released at >95% after 4?h. Moreover, the compound film had a statistically significant effect on mucosal repair and reduced ulcer inflammation without stimulating the human oral mucosa. C_max of OD in saliva was 37.04?μg/ml and that of DEX was 9.737?μg/ml. Given promising therapeutic effects, the compound film developed here could become a local drug delivery device for treating oral ulcers.     

Formulation and optimization of nanoemulsion using antifungal lipid and surfactant for accentuated topical delivery of Amphotericin B

The objective of the study was to develop, optimize and evaluate a nanoemulsion (NE) of Amphotericin B (AmB) using excipients with inherent antifungal activities (Candida albicans and Aspergillus niger) for topical delivery. AmB-loaded NE was prepared using Capmul PG8 (CPG8), labrasol and polyethylene glycol-400 by spontaneous titration method and evaluated for mean particle size, polydispersity index, zeta potential and zone of inhibition (ZOI). NE6 composed of CPG8 (15%w/w), S_mix (24%w/w) and water (61%w/w) was finally selected as optimized NE. AmB-NE6 was studied for improved in vitro release, ex vivo skin permeation and deposition using the Franz diffusion cell across the rat skin followed with drug penetration using confocal laser scanning microscopy (CLSM) as compared to drug solution (DS) and commercial Fungisome^®. The results of in vitro studies exhibited the maximum ZOI value of NE6 as 19.1?±?1.4 and 22.8?±?2.0?mm against A. niger and C. albicans, respectively, along with desired globular size (49.5?±?1.5?nm), zeta potential (?24.59?mV) and spherical morphology. AmB-NE6 revealed slow and sustained release of AmB as compared to DS in buffer solution (pH 7.4). Furthermore, AmB-NE6 elicited the highest flux rate (22.88?±?1.7?μg/cm²/h) as compared to DS (2.7?±?0.02?μg/cm²/h) and Fungisome^® (11.5?±?1.0?μg/cm²/h). Moreover, the enhancement ratio and drug deposition were found to be highest in AmB-NE6 than DS across the stratum corneum barrier. Finally, CLSM results corroborated enhanced penetration of the AmB-NE6 across the skin as compared to Fungisome^® and DS suggesting an efficient, stable and sustained topical delivery.     

Preparation and evaluation of dl-praeruptorin A microemulsion based hydrogel for dermal delivery

Abstract

The purpose of the present investigation was to develop and optimize the microemulsion (ME) as a transdermal system for Pd-Ia, a poor water soluble and low bioavailable drug. The pseudo-ternary phase diagrams were constructed for various ME formulations including oleic acid as the oil phase, Cremophor RH40 as the surfactant, ethanol as the cosurfactant, and water. The maximum cumulative amount permeated through rat abdominal skins per unit area in 32?h (Q₃₂), and the maximum flux were evaluated using the Franz diffusion cell in order to optimize the ME formulation. The results indicated that the optimized ME formulation was composed of oleic acid (5%, W/W), Cremophor RH40 (13.33%, W/W), ethanol (26.67%, W/W), and water (55%, W/W); the maximum cumulative amount of Pd-Ia was 354.330?±?12.006?μg?cm^?2, the maximum flux was 11.467?±?0.500?μg?cm^?2?h^?1. ME-gel was administered transdermally to rats. The mean plasma concentration of Pd-Ia following transdermal application of ME-gel could be maintained for 32?h at least and the half-life was evidently prolonged. It shows that the ME-gel could be a promising vehicle for dermal delivery of Pd-Ia.     

Investigation of true nanoemulsions for transdermal potential of indomethacin: characterization,rheological characteristics,and ex vivo skin permeation studies

The aim of the present study was to investigate the potential of true nanoemulsions for transdermal delivery of indomethacin. Thermodynamically stable true nanoemulsions were characterized for morphology using transmission electron microscopy (TEM), droplet size, rheological characteristics, and refractive index. The rheological behavior for all true nanoemulsions was found to be Newtonian as viscosity was unchanged by increasing the rate of shear. The ex vivo skin permeation studies were performed using Franz diffusion cell with rat skin as permeation membrane. The ex vivo skin permeation profile of optimized formulation was compared with marketed Indobene gel and nanoemulsion gel. Significant increase in permeability parameters was observed in nanoemulsion formulations (P?<?0.05). The steady-state flux (J_ss) and permeability coefficient (K_p) for optimized nanoemulsion formulation were found to be 73.96?±?2.89?μg/cm²/h and 1.479?×?10^?2?±?0.289?×?10^??2?cm/h, respectively, which were significant compared with Indobene gel and nanoemulsion gel (P?<?0.05). Enhancement ratio (E_r) was found to be 7.88 in optimized formulation F6 compared with other formulations. These results suggested that nanoemulsions can be used as potential vehicles for improved transdermal delivery of indomethacin.     

Optimization of nimesulide-loaded solid lipid nanoparticles (SLN) by factorial design,release profile and cytotoxicity in human Colon adenocarcinoma cell line

The aim of this work is development of a nontoxic, long-term stable solid lipid nanoparticles (SLN) formulation for the loading of Nimesulide (NiM) by a 2² factorial design. The optimized formulation was composed of 10?wt% of glyceryl behenate and 2.5?wt% of poloxamer 188. Immediately after production, Z-Ave of NiM-SLN was 166.1?±?0.114?nm, with a polydispersity index (PI) of 0.171?±?0051 and zeta potential nearly neutral (?3.10?±?0.166?mV). A slight increase of Z-Ave was recorded for NiM-SLN stored at 25?°C for a period of 15?days, whereas at 4?°C particles kept size within similar range. Long-term stability was monitored using TurbiscanLab^®, showing a high stability of the nanoparticles with variations in the backscattering profiles below 10%. The release profile of NiM-SLN followed a sustained pattern with ca. 30% of drug released up to 24?h. Empty-SLN and NiM-SLN were nontoxic after exposing Caco-2 cells to the highest concentration (100?μg/mL) up to 48?hours (cell viability higher than 80%). NiM-SLN were lyophilized using different cryoprotectants, producing particles of 463.1?±?36.63?nm (PI 0.491?±?0.027) with 5% trehalose. Solid character of NiM-SLN was confirmed by DSC, recording a recrystallization index of 83% for NiM-SLN and of 74% for lyophilized SLN.     

Evaluation of the cytotoxic effect of camptothecin solid lipid nanoparticles on MCF7 cells

Abstract

Camptothecin (CPT) and its analogs exhibit remarkable anti-tumor activity, due to their ability to inhibit DNA topoisomerase I. However, its use is limited by the lack of solubility and stability of the active lactone form. An attractive alternative is the encapsulation of CPT within liposomes. In this study, CPT was incorporated into solid lipid nanoparticles (SLN) based on the triglyceride, Compritol 888 ATO, using supercritical fluid technology without requiring the use of harmful solvents. This drug delivery system was characterized and its cytotoxicity effect was evaluated by measuring MCF7 and MCF10A cell viability as a function of drug loading during a 48-h treatment. Results showed that after 10?h of treatment, MCF7 cells displayed an IC50 of 0.23?±?0.034?μM at a 1:5 (CPT:SLN) loading and 0.22?±?0.027?μM at a 1:10 loading, whereas MCF10A cells displayed an IC50 of 0.40?±?0.036?μM at 1:5 and 0.60?±?0.063?μM at 1:10. On the other hand, the IC50 of free CPT was 0.57?±?0.035?μM and 1.07?±?0.077?μM for MCF7 and MCF10A cells, respectively. Cellular uptake and retention measurements in both cells displayed a two-fold increase when using the SLN formulation. The results from this study showed that the cytotoxic effects of CPT in a SLN formulation improved when compared with those seen with free CPT. The results of this study showed that delivery of CPT as a SLN formulation could be a promising strategy for enhancing its chemotherapeutic effects.     

Transdermal iontophoretic delivery of selegiline hydrochloride,in vitro

Transdermal iontophoretic delivery of selegiline hydrochloride (SH) across dermatomed human skin was studied. Electrochemical stability and various factors affecting the skin permeation were investigated. SH was stable under the influence of an electrical field. The permeation of SH was very low by passive delivery (2.29?±?0.05 μg/cm²/h) as compared to iontophoresis at 0.5 mA/cm² (65.10?±?5.04 μg/cm²/h). An increase in drug concentration from 1 to 20?mg/mL increased the iontophoretic flux by 13-fold. Optimal pH and salt (NaCl) concentration for iontophoretic delivery of SH were found to be pH 5 and 100?mM, respectively. Overall, with 20?mg/mL SH and a current density of 0.4 mA/cm², a maximum flux of 305.5?μg/cm²/h was obtained. Based on reported pharmacokinetic parameters, input target delivery rate to achieve effective plasma concentration of SH (2.2?ng/mL) was calculated. With a surface area of 40?cm², iontophoretic delivery can provide six to seven times higher levels of SH than the target delivery rate, which enables lowering of the dose and/or patch surface area. Further in vivo studies will be required to prove the efficacy of ionophoresis for enhanced delivery of SH.     

Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5-fluorouracil: a preliminary study

Abstract

Oral delivery of 5-fluorouracil (5-FU) is difficult due to its serious adverse effects and extremely low bioavailability. Therefore, the aim of present investigation was to develop and evaluate low HLB surfactant nanoemulsion of 5-FU for topical chemoprevention of skin cancer. Low HLB surfactant nanoemulsions were prepared by oil phase titration method. Thermodynamically stable nanoemulsions were characterized in terms of droplet size distribution, zeta potential, viscosity and refractive index. Selected formulations and control were subjected to in vitro skin permeation studies through rat skin using Franz diffusion cells. Optimized formulation F9 was subjected to stability and in vitro cytotoxic studies on melanoma cell lines. Enhancement ratio was found to be 22.33 in formulation F9 compared with control and other formulations. The values of steady state flux and permeability coefficient for formulation F9 were found to be 206.40?±?14.56?µg?cm^?2?h^?1 and 2.064?×?10^?2?±?0.050?×?10^?2?cm?h^?1, respectively. Optimized formulation F9 was found to be physical stable. In vitro cytotoxicity studies on SK-MEL-5 cancer cells indicated that 5-FU in optimized nanoemulsion is much more efficacious than free 5-FU. From these results, it can be concluded that the developed nanoemulsion might be a promising vehicle for chemoprevention of skin cancer.