Glucosamine anchored cancer targeted nano-vesicular drug delivery system of doxorubicin

Background: Efficacy of an anticancer drug is challenged by severe adverse effects persuaded by the drug itself; hence designing a tumour targeted delivery system is chosen as an objective of this research work.

Purpose: We propose, glucose transporter targeting ligand, i.e. synthesised N-lauryl glucosamine (NLG) anchored doxorubicin (DOX) in niosomal formulation.

Methods: Synthesised NLG was incorporated into niosomal formulation of DOX using Span 60 as surfactant, cholesterol as membrane stabilizer and dicetyl phosphate (DCP) as stabilizer.

Results: The formulation was stable with particle size of 110?±?5?nm, zeta potential ?30?±?5?mV and entrapment efficiency approximately 95%. DSC and XRD pattern of freeze-dried formulation demonstrated encapsulation of DOX in niosomal formulation. Cytotoxicity of targeted niosomal formulation (IC₅₀?=?0.830?ppm) was higher than non-targeted niosomal formulation (IC₅₀?=?1.369?ppm) against B6F10 melanoma cell lines. In vitro cellular internalization revealed that targeted niosomal formulation was internalised more efficiently with higher cellular retention by cancer cells compared to the non-targeted niosomal formulation and free DOX. In vitro receptor binding and docking study of targeted niosomal formulation had shown the comparative association potential with glucose receptor.

Conclusion: NLG anchored niosomal formulation of DOX with enhanced cytotoxicity, internalization and receptor binding potential has implication in targeted cancer therapy.     

Transdermal delivery of meloxicam using niosomal hydrogels: in vitro and pharmacodynamic evaluation

Abstract

Non-ionic surfactant vesicles were prepared using Span-60 and cholesterol in the mass ratios of 1:1, 2:1, 1:2 and 3:1 for transdermal delivery of an anti-inflammatory drug meloxicam (MXM). The drug encapsulation efficiencies and particle size were observed in the range of 32.9–80.7% and 56.5–133.4?nm, respectively. Three different gel bases were also prepared using Poloxamer-407, Chitosan and Carbopol-934 as polymers to study the performance of the in vitro release of the drug. Prepared gels were also converted into niosomal gels. In vitro release characteristics of MXM from different gels were carried out using dialysis membrane in phosphate buffer (pH 7.4). The poloxamer-407 gel or niosomal poloxamer-407 gel showed the superior drug release over the other formulations. The release data were treated with various mathematical models to assess the relevant parameters. The results showed that the release of MXM from the prepared gels and niosomal gels followed Higuchi’s diffusion model. The flux of MXM was found to be independent on the viscosity of the formulations. The anti-inflammatory effects of MXM from different niosomal gel formulations were evaluated using carrageenan-induced rat paw edema method, which showed superiority of niosomal gels over conventional gels.     

Nebulized Interleukin 2 Liposomes: Aerosol Characteristics and Biodistribution

Although interleukin 2 (IL-2) has been associated with modest anti-tumour responses in man, treatment-related toxicity has limited its widespread use. The local delivery of liposomal formulations of interleukin 2 to the lung as aerosols has been demonstrated to be non-toxic, biologically active, and associated with regression of spontaneous pulmonary metastases in dogs. This study was undertaken to evaluate the physical and biological characteristics of nebulized interleukin 2 liposomes. The aerosol droplet size distribution and the physical stability of interleukin 2 liposomes were examined in-vitro using an Andersen cascade impactor and studies of liposome entrapment of interleukin 2 before and after nebulization. The biological stability of interleukin 2 liposomes after nebulization was demonstrated using the CTLL-2 bioassay for interleukin 2. In-vivo studies of pulmonary biodistribution and clearance of inhaled technetium (^99mTc)-labelled interleukin 2 liposomes were undertaken in a normal dog. Aerosols of free interleukin 2 and of interleukin 2 liposomes were compared in both in-vitro and in-vivo experiments. The mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of interleukin 2 liposomes were 1–98 μm and 202, respectively. Independent analysis of aerosol particle-size distribution using the constitutive components of the interleukin 2 liposomes (interleukin 2: lipid: HSA) demonstrated a close correlation of size distributions (r = 0.9445; P < 0.001). The entrapment of interleukin 2 in liposomes was 93 ± 4.3% before nebulization and 90 ± 8.9% after. After delivery to an anaesthetized dog, interleukin 2 liposome aerosols were deposited evenly throughout the lung (mean ± s.d. central lung-to-peripheral lung deposition was 1–12 ± 0.03). After approximately 24 h inhalation, interleukin 2 liposomes were retained within the lung and were taken up in part by the spleen. The results of this study are indicative of the stability of this interleukin 2 liposome formulation to nebulization. Such nebulization might be an attractive immunotherapeutic strategy for treatment of pulmonary metastases and primary lung cancers.     

Development of a biocompatible creatinine-based niosomal delivery system for enhanced oral bioavailability of clarithromycin

Context: Nonionic surfactant vesicles have gained increasing scientific attention for hydrophobic drugs delivery due to their biocompatibility, stability and low cost.

Objective: The aim of the present study was to synthesize and evaluate a novel creatinine-based nonionic surfactant in terms of its ability to generate biocompatible niosomal system for the delivery of Clarithromycin.

Materials and Methods: The surfactant was synthesized by reacting creatinine with lauroyl chloride followed by characterization using ¹HNMR and MS. The drug-loaded niosomal vesicles of the surfactant were characterized for drug encapsulation efficiency (EE) using LC-MS, vesicle size using dynamic light scattering (DLS) and vesicle shape using atomic force microscopy (AFM). The surfactant was also investigated for blood hemolysis, in vitro cytotoxicity against different cell lines and in vivo acute toxicity in mice. Furthermore, the in vivo bioavailability of Clarithromycin encapsulated in the novel niosomal formulation was investigated using rabbits and quantified through validated LC-MS/MS method.

Results and discussion: Findings showed that vesicles were able to entrap up to 67.82?±?1.27% of the drug, and were rounded in shape with a size around 202.73?±?5.30?nm and low polydispersity. The surfactant caused negligible blood hemolysis, very low cytotoxicity and was found to be safe up to 2500?mg/kg body weight using mice. The niosomal formulation showed twofold enhanced oral bioavailability of Clarithromycin as compared to commercial formulations of the drug.

Conclusion: The study has shown that the creatinine-based niosomes developed in our laboratory were biocompatible, safe and increased the oral bioavailability of the model hydrophobic Clarithromycin using experimental animals.     

Preparation and evaluation of niosomes containing autoclaved Leishmania major: a preliminary study

In this study, different positively charged niosomal formulations containing sorbitan esters, cholesterol and cetyl trimethyl ammonium bromide were prepared by film hydration method for the entrapment of autoclaved Leishmania major (ALM). Size distribution pattern and stability of niosomes were investigated by laser light scattering method and ALM encapsulation per cent was measured by the bicinchoninic acid method. Finally, the selected formulation was used for the induction of the immune response against cutaneous leishmaniasis in BALB/c mice. Size distribution curves of all the formulations followed a log-normal pattern and the mean volume diameter was in the range 7.57–15.80?µm. The mean volume diameters were significantly increased by adding Tween to Span formulations (p?<?0.05). The percentage of ALM entrapped in all formulations varied between 14.88% and 36.65%. In contrast to ALM, in vivo studies showed that the niosomes containing ALM have a moderate effect in the prevention of cutaneous leishmaniasis in BALB/c mice.     

Characterization of niosomes prepared with various nonionic surfactants for paclitaxel oral delivery

Nonionic surfactant based vesicles (niosomes) are novel drug delivery systems formed from the self‐assembly of nonionic amphiphiles in aqueous media. In the present study niosomal formulations of Paclitaxel (PCT), an antineoplastic agent, were prepared using different surfactants (Tween 20, 60, Span 20, 40, 60, Brij 76, 78, 72) by film hydration method. PCT was successfully entrapped in all of the formulations with encapsulation efficiencies ranging between 12.1 ± 1.36% and 96.6 ± 0.482%. Z‐average sizes of the niosomes were between 229.3 and 588.2 nm. Depending on the addition of the negatively charged dicetyl phosphate to the formulations negative zeta potential values were obtained. High surface charges showed that niosomes can be suspended in water well and this is beneficial for their storage and administration. PCT released from niosomes by a diffusion controlled mechanism. The slow release observed from these formulations might be beneficial for reducing the toxic side effects of PCT. The niosome preparation method was found to be repeatable in terms of size distribution, zeta potential and % drug loading values. The efficiency of niosomes to protect PCT against gastrointestinal enzymes (trypsin, chymotrypsin, and pepsin) was also evaluated for PCT oral delivery. Among all formulations, gastrointestinal stability of PCT was well preserved with Span 40 niosomes. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2049–2060, 2010     

Nebulization of niosomal all-trans-retinoic acid: an inexpensive alternative to conventional liposomes

In this study we have demonstrated the potential of encapsulating all-trans-retinoic acid (ATRA) in niosomes and delivering it as an inhaled aerosol. Niosomes may provide a means to reduce the toxicity of ATRA and alter the pharmacokinetics in a manner similar to liposomes. In addition, the low cost of the surfactants used for preparing niosomes and their greater stability compared with liposomes makes them an attractive alternative. Various nonionic surfactants were used to achieve optimum encapsulation and nebulization efficiencies, and the best formulations were obtained with combinations of (Span 20 + Tween 80) and (Span 60 + Tween 80) using an ATRA concentration of 1 mg/ml. The aerosol produced with the selected niosomal formulations upon nebulization in PARI LC STAR nebulizers driven by a Pulmo-Aide compressor was subsequently analyzed for the determination of size distribution and entrapment efficiencies on each stage of an Anderson cascade impactor operated in a manner that avoids spurious sizing due to droplet evaporation. Mass median aerodynamic diameters (MMADs) of 3.7+/-0.3 and 3.58+/-0.03 microm, geometric standard deviation (GSD) values of 1.59+/-0.17 and 1.51+/-0.01 and entrapment efficiencies well above 50% were obtained for the optimized formulations. The results are very encouraging and offer an alternative approach to the respiratory delivery of ATRA by aerosolization.     

Formulation and evaluation of metformin hydrochloride-loaded niosomes as controlled release drug delivery system

Abstract

Lactic acidosis is a serious, metabolic complication that may occur due to metformin hydrochloride (MH) accumulation during the treatment of diabetes mellitus. The aim of this study is to enhance the bioavailability of MH by oral route. Span 40 and cholesterol were used for the preparation of MH-loaded niosomes by the reverse phase evaporation technique. Dicetyl phosphate (DCP) and 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) were used to obtain negatively and positively charged vesicles, respectively. The mean particle size ranged from 223.5 to 384.6?nm and the MH-loaded niosomes’ surface was negatively charged in the absence of charge inducing agents (?16.6?±?1.4?mV) and also with DCP (?26.9?±?1.0?mV), while it was positively charged (+8.7?±?1.2?mV) with DOTAP. High entrapment efficiency was observed in all the formulations. MH-loaded niosomes were found to effectively sustain the release of drug, particularly with positively charged niosomes. The bioavailability of MH-loaded niosomes was assessed by measuring the serum values of glucose and metformin in the different studied Wistar rats groups. The pharmacokinetic data of MH-loaded niosomal preparation showed a significant prolongation and increased intensity of hypoglycemic effect more than that observed for free MH solution. Area above the blood glucose levels–time curve (AAC), maximum hypoglycemic response and time of maximum response (T_max) were significantly higher (p?<?0.001) when MH was administered in niosomal form compared to free drug solution. It could be concluded that MH-loaded niosome is promising extended-release preparation with better hypoglycemic efficiency.     

Influence of particle size on drug delivery to rat alveolar macrophages following pulmonary administration of ciprofloxacin incorporated into liposomes

In order to confirm the efficacy of ciprofloxacin (CPFX) incorporated into liposomes (CPFX–liposomes) for treatment of respiratory intracellular parasite infections, the influence of particle size on drug delivery to rat alveolar macrophages (AMs) following pulmonary administration of CPFX–liposomes was investigated. CPFX–liposomes were prepared with hydrogenated soybean phosphatidylcholine (HSPC), cholesterol (CH) and dicetylphosphate (DCP) in a lipid molar ratio of 7/2/1 by the hydration method and then adjusted to five different particle sizes (100, 200, 400, 1000 and 2000 nm). In the pharmacokinetic experiment, the delivery efficiency of CPFX to rat AMs following pulmonary administration of CPFX–liposomes increased with the increase in the particle size over the range 100–1000 nm and became constant at over 1000 nm. The concentrations of CPFX in rat AMs until 24 h after pulmonary administration of CPFX–liposomes with a particle size of 1000 nm were higher than the minimum inhibitory concentration of CPFX against various intracellular parasites. In a cytotoxic test, no release of lactate dehydrogenase (LDH) from rat lung tissues by pulmonary administration of CPFX–liposomes with a particle size of 1000 nm was observed. These findings indicate that efficient delivery of CPFX to AMs by CPFX–liposomes with a particle size of 1000 nm induces an excellent antibacterial effect without any cytotoxic effects on lung tissues. Therefore, CPFX–liposomes may be useful in the development of drug delivery systems for the treatment of respiratory infections caused by intracellular parasites, such as Mycobacterium tuberculosis, Chlamydia pneumoniae and Listeria monocytogenes.     

Formulation and evaluation of meloxicam niosomes as vesicular carriers for enhanced skin delivery

Context: Skin delivery of Meloxicam (MX) offers several advantages over the oral route which is associated with potential side effects.

Objectives: The aim of this study was to develop transdermal MX in niosomes.Materials and Methods: Vesicles prepared by thin film hydration method were characterized and the acute anti-inflammatory activity of 0.5% MX niosomal hydrogel was evaluated using carrageenan induced rat paw edema method. Results: The results revealed that niosomes prepared from span 60 and cholesterol at 6:4 molar ratio using 20?mg of MX were of the highest entrapment efficiency (> 55%) and with particle size (187.3?nm). There was a marked increase in the percentage inhibition of edema in animals treated with MX vesicular gel compared to those treated with free MX and piroxicam gels.

Discussion: There was an inverse proportionality between vesicle size and cholesterol content. With increased cholesterol molar ratio the bilayer stability increased and permeability decreased leading to efficiently trapping the MX. In contrast, higher amounts of cholesterol may compete with the drug for packing space within the bilayer. The inhibitory effect of MX niosomal gel may be attributed to its superior skin permeation.

Conclusions: The results suggest that niosomes may be promising vehicles for transdermal delivery of MX.     

Development of Respirable Nanomicelle Carriers for Delivery of Amphotericin B by Jet Nebulization

The aim of the present work was to prepare and characterize chitosan-stearic acid conjugate nanomicelles for encapsulation of amphotericin B (AmB) and to evaluate the in vitro nebulization of the formulations. Water soluble chitosan was grafted to stearic acid (SA) chains via 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide mediated coupling reaction. The chemical structure of depolymerized chitosan (DC)-SA copolymers and degree of amino substitution was determined by ¹H NMR. AmB was loaded in nanomicelles with a maximal encapsulation efficiency of 97%. The physicochemical properties and formation of polymeric micelles were studied by dynamic light scattering and fluorescence spectroscopy method. Nanomicelles possessed positive charges with mean particle sizes of 101–248 nm. AmB-loaded micelles were also characterized for their antifungal activity, aggregation state of the drug, nebulization efficiency and retention of AmB in the micelles after nebulization. The results indicated that encapsulation of AmB in DC-SA micelles could improve the antifungal activity of the drug in some of the cases. The nebulization efficiency was up to 56% and the fine particle fraction (FPF) varied from 40% to 52%. Since there was only a little change in encapsulation of the drug in micelles after nebulization, DC-SA micellar formulations can be a suitable choice for pulmonary delivery of AmB.     

Nebulization of ultradeformable liposomes: The influence of aerosolization mechanism and formulation excipients

Ultradeformable liposomes are stress-responsive phospholipid vesicles that have been investigated extensively in transdermal delivery. In this study, the suitability of ultradeformable liposomes for pulmonary delivery was investigated. Aerosols of ultradeformable liposomes were generated using air-jet, ultrasonic or vibrating-mesh nebulizers and their stability during aerosol generation was evaluated using salbutamol sulphate as a model hydrophilic drug. Although delivery of ultradeformable liposome aerosols in high fine particle fraction was achievable, the vesicles were very unstable to nebulization so that up to 98% drug losses were demonstrated. Conventional liposomes were relatively less unstable to nebulization. Moreover, ultradeformable liposomes tended to aggregate during nebulization whilst conventional vesicles demonstrated a "size fractionation" behaviour, with smaller liposomes delivered to the lower stage of the impinger and larger vesicles to the upper stage. A release study conducted for 2h showed that ultradeformable liposomes retained only 30% of the originally entrapped drug, which was increased to 53% by inclusion of cholesterol within the formulations. By contrast, conventional liposomes retained 60-70% of the originally entrapped drug. The differences between ultradeformable liposomes and liposomes were attributed to the presence of ethanol or Tween 80 within the elastic vesicle formulations. Overall, this study demonstrated, contrary to our expectation, that materials included with the aim of making the liposomes more elastic and ultradeformable to enhance delivery from nebulizers were in fact responsible for vesicle instability during nebulization and high leakage rates of the drug.     

Evaluation of proniosomes as an alternative strategy to optimize piroxicam transdermal delivery

The current investigation aims to evaluate the transdermal potential of niosomes bearing a potent non-steroidal anti-inflammatory, piroxicam. Piroxicam-loaded niosomes were prepared and characterized for surface morphology, entrapment efficiency and in vitro permeation across excised rat skin from various proniosome gel formulations using Franz diffusion cells. Various non-ionic surfactants were used to achieve optimum encapsulation efficiency. The prepared proniosomes significantly improved drug permeation and reduced the lag time (p < 0.05). Proniosomes prepared with Span 60 provided a higher piroxicam flux across the skin than did those prepared with Tween 80. Niosomes prepared using Span 60 showed a higher release rate than those prepared using non-ionic surfactants, Span 20 and Span 80, while those prepared from Tween showed higher release rate than formula prepared with Span. This indicates that lipophilicity and hydrophilicity of surfactant has a main role in release rates of piroxicam. Particle size of piroxicam niosomal vesicles formed by proniosome was determined by scanning electron microscopy. The encapsulation efficiency was evaluated by a specific high performance liquid chromatography method. Niosomes formed from using Spans and Tweens exhibited very high encapsulation efficiency. The results are very encouraging and suggest that niosomes can act as promising carriers offering an alternative approach for transdermal delivery of piroxicam.     

Sugar-based novel niosomal nanocarrier system for enhanced oral bioavailability of levofloxacin

Context: Vesicular systems have attracted great attention in drug delivery because of their amphiphilicity, biodegradability, non-toxicity and potential for increasing drug bioavailability.

Objective: A novel sugar-based double-tailed surfactant containing renewable block was synthesized for preparing niosomal vesicles that could be exploited for Levofloxacin encapsulation, aiming to increase its oral bioavailability.

Materials and methods: The surfactant was characterized by ¹H NMR, mass spectroscopy and Fourier transform infrared spectroscopy (FT-IR). Its biocompatibility was studied against cell cultures and human blood hemolysis. In vivo acute toxicity was evaluated in mice. The vesicle morphology, size, drug-excipients interaction and entrapment efficiency (EE) were examined using atomic force microscope (AFM), dynamic light scattering (DLS), FT-IR and HPLC. Oral bioavailability studies of Levofloxacin in surfactant-based niosomal formulation were carried out using rabbits and plasma samples were analyzed using HPLC.

Results and discussion: Vesicles were spherical in shape and the size was 190.31?±?4.51?nm with a polydispersity index (PDI) of 0.29?±?0.03. The drug EE in niosomes was 68.28?±?3.45%. When applied on cell lines, high cell viability was observed even after prolonged exposure at high concentrations. It caused 5.77?±?1.34% hemolysis at 1000?μg/mL and was found to be safe up to 2000?mg/kg. Elevated Levofloxacin plasma concentration was achieved when delivered with novel vesicles.

Conclusion: The surfactant was demonstrated to be safe and effective as carrier of Levofloxacin. The study suggests that this sugar-based double-tailed nonionic surfactant could be promising nano-vesicular system for delivery and enhancing oral bioavailability of the hydrophobic Levofloxacin.     

Niosomes with Sorbitan Monoester as a Carrier for Vaginal Delivery of Insulin: Studies in Rats

To prepare and investigate the potential of the niosomes vaginal delivery system for systemic treatment of insulin is the goal of this study. Two kinds of vesicles with Span 40 and Span 60 were prepared by lipid phase evaporation methods with sonication. The niosomal entrapment efficiency was determined by column chromatography. The particle size and morphology of the vesicles also were evaluated. The results showed optimized niosomes prepared in this study had niosomal entrapment efficiency 26.68 ± 1.41% for Span 40 and 28.82 ± 1.35% for Span 60, respectively. The particle sizes of Span 40 niosomes and Span 60 niosomes were 242.5 ± 20.5 nm and 259.7 ± 33.8 nm, respectively. There were no significant differences in appearance between the two types of vesicles. The hypoglycemic effects, and insulin concentrations after vaginal administration of insulin vesicles to rats were investigated. Compared with subcutaneous administration of insulin solution, the relative pharmacological bioavailability and the relative bioavailability of vaginal administration of insulin vesicles were determined. Compared with subcutaneous administration of insulin solution, the relative pharmacological bioavailability and the relative bioavailability of insulin-Span 60 vesicles group were 8.43% and 9.61%, and insulin-Span 40 niosomes were 9.11% and 10.03% (p > 0.05). Span 60 and Span 40 niosomes were both higher than blank Span 40, Span 60 vesicles, and free insulin physical mixture groups (p < 0.05). The results indicates insulin-Span 60, Span 40 niosomes had an enhancing effect on vaginal delivery of insulin. Although the factors controlling the process for penetration of a portion of vaginally administrated niosomes into bloodstream from vaginal tract is still not fully understood, our results demonstrated that after encapsulation in niosomes of definite type, insulin became an active and efficiently therapeutic agent when administrated vaginally and might be a good carrier for vaginal delivery of protein drugs.     

Caffeine-loaded niosomes: characterization and in vitro release studies

We prepared different neutral and positively charged niosomal formulations containing sorbitan esters for entrapment of caffeine. Drug entrapment reduced following the incorporation of positively charged molecule. Furthermore, the span 60-containing niosomes showed the highest drug encapsulation efficiency due to solid-state nature of this surfactant's bilayers. There was a regular relationship between lipophilicity (HLB values) of surfactants and mean particle sizes; increasing the HLB value resulted in larger niosomes. By means of diffusion experiments with Franz diffusion cells, the effects of different vesicular components and that of the positive charge on the release of caffeine from various vesicle formulations were studied. Obtained results indicate that a combined erosion-diffusion mechanism regulates the permeation of caffeine through cellulose acetate membranes. High encapsulation efficiency, appropriate size distribution, and good vesicular stability, especially in solid state niosomes, make this type of vesicular systems a good alternative to liposomes for topical delivery of caffeine.     

Enhanced ocular bioavailability of fluconazole from niosomal gels and microemulsions: formulation,optimization, and in vitro–in vivo evaluation

Fungal keratitis may cause vision loss if it is not treated. Methods other than ocular delivery exhibited several limitations. No previous studies investigated and compared ocular bioavailability of fluconazole (FLZ) from niosomal gels and microemulsions. Niosomal gels of FLZ (0.3% w/w) based on Span^® 60 and cholesterol (CH) using 1% w/w carbopol^® 934 (CP) were evaluated. FLZ microemulsions (0.3% w/v) containing isopropyl myristate (IPM, as oil phase) and a 3:1 mixture of Tween^® 80 (as surfactant) and polyethylene glycol 400 (PEG 400, as cosurfactant) were characterized. Optimized formulations were compared for their ocular bioavailability in rabbit’s. Nanoscopic niosomes (63.67–117.13?nm) and microemulsions (57.05–59.93?nm) showed respective negative zeta potential ranges of ?45.37 to ?61.40 and ?20.50 to ?31.90?mV and sustained release up to 12?h. Entrapment efficiency (EE%) of niosomes ranged from 56.48% to 70.67%. Niosomal gels were more sustainable than niosomes and microemulsions. The most stable niosomal gel based on Span^® 60 and CH at a molar ratio of 5:5 and microemulsion containing 45% w/w IPM and 40% w/w of 3:1 Tween^® 80-PEG 400 mixture significantly (p?<?0.0001) enhanced FLZ ocular bioavailability compared with its solution. Niosomal gel showed higher bioavailability than microemulsion by ≈2-fold.     

Magnesium ascorbyl phosphate vesicular carriers for topical delivery; preparation,in-vitro and ex-vivo evaluation,factorial optimization and clinical assessment in melasma patients

Ascorbic acid (vitamin C) is an antioxidant that is widely used in cosmetics in skincare products. Due to the excessive low stability of ascorbic acid in cosmetic formulations, the stabilized ascorbic acid derivative, magnesium ascorbyl phosphate (MAP) was formulated as vesicular carriers; ethosomes and niosomes. The aim was to deliver MAP at the intended site of action, the skin, for sufficient time with enhanced permeation to get an effective response. Ethosomes were formulated using a full 3² factorial design to study ethanol and phospholipid concentration effect on ethosomes properties. Niosomes were formulated using 2³ factorial designs to study the effect of surfactant type, surfactant concentration and cholesterol concentration on niosomes properties. The prepared formulations were evaluated for their Entrapment efficiency, particle size, polydispersity index, zeta potential and % drug permeated. The optimized ethosomal and niosomal formulations were incorporated into carbopol gel and evaluated for their permeation, skin retention and stability. A comparative split-face clinical study was done between the ethosomal and niosomal formulations for melasma treatment using Antera 3 D^® camera. The optimized ethosomal and niosomal gels showed comparable controlled permeation and higher skin retention over their ethosomes and niosomes formulations respectively. Magnesium ascorbyl phosphate ethosomal gel showed clinically and statistically significant melanin level decrease after one month while MAP niosomal gel showed clinically and statistically significant melanin level decrease after six months. A combination of MAP ethosomes and niosomes could be promising skincare formulations for melasma and hyperpigmentation short and long-term treatment.     

Amphotericin B-loaded polymeric nanoparticles: formulation optimization by factorial design

In this study, PLGA or PLGA-PEG blend nanoparticles were developed loading amphotericin B (AmB), an antifungal agent broadly used in therapy. A 2²?×?3¹ factorial experimental design was conducted to indicate an optimal formulation of nanoparticles containing AmB and demonstrate the influence of the interactions of components on the mean particle size and drug encapsulation efficiency. The independent variables analyzed were polymer amount (two levels) and organic phase (three factors in one level). The parameters methanol as cosolvent and higher polymer amount originated from the higher AmB encapsulation, but with the larger particle size. The selected optimized parameters were set as the lower polymer amount and ethyl acetate as cosolvent in organic phase, for both PLGA and PLGA-PEG nanoparticles. These parameters originated from nanoparticles with the size of 189.5?±?90?nm and 169?±?6.9?nm and AmB encapsulation efficiency of 94.0?±?1.3% and 92.8?±?2.9% for PLGA and PLGA-PEG nanoparticles, respectively. Additionally, these formulations showed a narrow size distribution indicating homogeneity in the particle size. PLGA and PLGA-PEG nanoparticles are potential carrier for AmB delivery and the factorial design presented an important tool in optimizing nanoparticles formulations.