Elastic Liposomal Formulation for Sustained Delivery of Antimigraine Drug: In Vitro Characterization and Biological Evaluation

The aim of this study was to prepare and characterize a topical formulation for sustained delivery of rizatriptan. Elastic liposomal formulation of rizatriptan was prepared and characterized for different characteristics by evaluating in vitro and in vivo parameters. The in vivo performance of optimized formulation was evaluated for antimigraine activity in mice using morphine withdrawal-induced hyperalgesia. The in vitro skin permeation study across rat skin suggested carrier-mediated transdermal permeation for different elastic liposomal formulation to range between 18.1 ± 0.6 and 42.7 ± 2.3 μg/h/cm², which was approximately 8–19 times higher than that obtained using drug solution. The amount of drug deposited was 10-fold higher for elastic liposome (39.9 ± 3.2%) than using drug solution (3.8 ± 1%); similarly the biological activity of optimized elastic liposome formulation was found to be threefold higher than the drug solution. On the basis of the results, it can be concluded that the elastic liposomal formulation provided sustained action of rizatriptan due to depot formation in the deeper layer of skin.     

Chitosan-based thermosensitive hydrogel containing liposomes for sustained delivery of cytarabine

Sustained release thermosensitive solution containing cytarabine-loaded liposome delivery system offers the possibility of reduced dosing frequency and sustained drug action. Biodegradable and biocompatible chitosan-beta-glycerophosphate (C-GP) thermosensitive solution having the property to gel at body temperature and to maintain its physical integrity for longer period of time was used. The C-GP solution containing cytarabine-loaded liposomes (CGPCLL) was studied, and the results showed that the cytarabine liposomes were capable of high encapsulation efficiency (85.2 +/- 2.58%) with the mean diameter of 220 +/- 6.9 nm of extruded cytarabine-loaded liposome. Furthermore, transmission electron microscopy showed spherical-shaped liposomes after extrusion with smooth surface. In vitro studies of CGPCLL in PBS buffer showed that this system can sustain release of encapsulated drug for more than 60 h compared with drug-loaded liposomal suspension (upto 48 h). Pharmacokinetic studies of CGPCLL resulted in higher t(1/2) (28.86 h) and AUC 2526.88 mug/mL h compared with cytarabine-loaded liposomal suspension (CLLS) and C-GP containing free cytarabine (CGPFC) in rats. CGPCLL was capable of sustaining the cytarabine release for more than 60 h in vivo compared with CLLS and CGPFC which showed maximum amount of drug release within 42 and 10 h, respectively. Thus, these results showed that the CGPCLL gels at body temperature and can sustain the delivery of cytarabine effectively.     

Development of a liposome microbicide formulation for vaginal delivery of octylglycerol for HIV prevention

The feasibility of using a liposome drug delivery system to formulate octylglycerol (OG) as a vaginal microbicide product was explored. A liposome formulation was developed containing 1% OG and phosphatidyl choline in a ratio that demonstrated in vitro activity against Neisseria gonorrhoeae, HSV-1, HSV-2 and HIV-1 while sparing the innate vaginal flora, Lactobacillus. Two conventional gel formulations were prepared for comparison. The OG liposome formulation with the appropriate OG/lipid ratio and dosing level had greater efficacy than either conventional gel formulation and maintained this efficacy for at least 2 months. No toxicity was observed for the liposome formulation in ex vivo testing in a human ectocervical tissue model or in vivo testing in the macaque safety model. Furthermore, minimal toxicity was observed to lactobacilli in vitro or in vivo safety testing. The OG liposome formulation offers a promising microbicide product with efficacy against HSV, HIV and N. gonorrhoeae.     

Chitosan-Based Thermosensitive Hydrogel Containing Liposomes for Sustained Delivery of Cytarabine

Sustained release thermosensitive solution containing cytarabine-loaded liposome delivery system offers the possibility of reduced dosing frequency and sustained drug action. Biodegradable and biocompatible chitosan-beta-glycerophosphate (C-GP) thermosensitive solution having the property to gel at body temperature and to maintain its physical integrity for longer period of time was used. The C-GP solution containing cytarabine-loaded liposomes (CGPCLL) was studied, and the results showed that the cytarabine liposomes were capable of high encapsulation efficiency (85.2?±?2.58%) with the mean diameter of 220?±?6.9 nm of extruded cytarabine-loaded liposome. Furthermore, transmission electron microscopy showed spherical-shaped liposomes after extrusion with smooth surface. In vitro studies of CGPCLL in PBS buffer showed that this system can sustain release of encapsulated drug for more than 60 h compared with drug-loaded liposomal suspension (upto 48 h). Pharmacokinetic studies of CGPCLL resulted in higher t_1/2 (28.86 h) and AUC 2526.88 μg/mL h compared with cytarabine-loaded liposomal suspension (CLLS) and C-GP containing free cytarabine (CGPFC) in rats. CGPCLL was capable of sustaining the cytarabine release for more than 60 h in vivo compared with CLLS and CGPFC which showed maximum amount of drug release within 42 and 10 h, respectively. Thus, these results showed that the CGPCLL gels at body temperature and can sustain the delivery of cytarabine effectively.     

Enhanced oral bioavailability and intestinal lymphatic transport of a hydrophilic drug using liposomes

A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.     

Enhanced Oral Bioavailability and Intestinal Lymphatic Transport of a Hydrophilic Drug Using Liposomes

ABSTRACT

A liposome system was evaluated for oral delivery of a poorly bioavailable hydrophilic drug. The system was prepared from proliposome, which consisted of negatively charged phosphatidylcholine, whereas cefotaxime was chosen as the model drug. An in vivo study was carried out on nine rats according to a three-way crossover design to compare the oral bioavailability of cefotaxime from the liposomal formulation with that of an aqueous drug solution and a physical mixture of cefotaxime with blank liposomes. The results indicated that the extent of bioavailability of cefotaxime was increased approximately 2.7 and 2.3 times compared with that of the aqueous solution and the physical mixture, respectively. In a separate study, simultaneous determination of cefotaxime in intestinal lymph (collected from the mesenteric lymph duct) and in plasma (collected from the tail vein) revealed that its concentration was consistently higher in the lymph than in the plasma when administered via the liposomal formulation, whereas the reverse was observed with the aqueous solution. Thus, the results indicated that the liposomes system has the potential of increasing the oral bioavailability of poorly bioavailable hydrophilic drugs and also promote their lymphatic transport in the intestinal lymph.     

Nanocarrier-based topical drug delivery for an antifungal drug

Objective: The conventional liposomal amphotericin B causes many unwanted side effects like blood disorder, nephrotoxicity, dose-dependent side effects, highly variable oral absorption and formulation-related instability. The objective of the present investigation was to develop cost-effective nanoemulsion as nanocarreir for enhanced and sustained delivery of amphotericin B into the skin.

Methods and characterizations: Different oil-in-water nanoemulsions were developed by varying the composition of hydrophilic (Tween® 80) surfactants and co-surfactant by the spontaneous titration method. The developed formulation were characterized, optimized, evaluated and compared for the skin permeation with commercial formulation (fungisome 0.01% w/w). Optimized formulations loaded with amphotericin B were screened using varied concentrations of surfactants and co-surfactants as decided by the ternary phase diagram.

Results and discussion: The maximum % transmittance obtained were 96.9?±?1.0%, 95.9?±?3.0% and 93.7?±?1.2% for the optimized formulations F-I, F-III and F-VI, respectively. These optimized nanoemulsions were subjected to thermodynamic stability study to get the most stable nanoemulsions (F-I). The results of the particle size and zeta potential value were found to be 67.32?±?0.8 nm and –3.7?±?1.2?mV for the final optimized nanoemulsion F-I supporting transparency and stable nanoemulsion for better skin permeation. The steady state transdermal flux for the formulations was observed between 5.89?±?2.06 and 18.02?±?4.3?µg/cm²/h whereas the maximum enhancement ratio were found 1.85- and 3.0-fold higher than fungisome and drug solution, respectively, for F-I. The results of the skin deposition study suggests that 231.37?±?3.6?µg/cm² drug deposited from optimized nanoemulsion F-I and 2.11-fold higher enhancement ratio as compared to fungisome. Optimized surfactants and co-surfactant combination-mediated transport of the drug through the skin was also tried and the results were shown to have facilitated drug permeation and skin perturbation (SEM).

Conclusion: The combined results suggested that amphotericin B nanoemulsion could be a better option for localized topical drug delivery and have greater potential as an effective, efficient and safe approach.     

High-Entrapment Liposomes for 6-Mercaptopurine—A Prodrug Approach

Low entrapment of drugs into liposomes is a serious challenge in their commercial application. 6-Mercaptopurine (6-MP), an antineoplastic agent, is such a drug with low entrapment efficiency (EE). We devised their lipophilic derivatization as a means of enhancing EE by covalently coupling 6-MP with glyceryl monostearate (GMS) via a succinic anhydride spacer. This prodrug had an improved partition coefficient value of 25.16 compared to 1.22 for free drug, confirming higher lipophilicity. A hydrolysis rate study of prodrug indicated 2.90%, 12.5%, 24.1%, and 25.1% hydrolysis in phosphate buffered saline (PBS) (pH 7.4) and 10%, 20%, and 30% serum, respectively. Liposomes of phosphatidylcholine (PC)/sphingomyelin, cholesterol, and dicetyl phosphate bearing drug or prodrug were prepared by shaking by hand and sonication methods. The EE was found to increase from 1.92% for free drug to 91.8% for drug-conjugate. An in vitro cell line toxicity study on L1210 leukemia cells showed improved performance of liposome-encapsulated drug-conjugate compared to free drug. The plasma drug level profile following administration of free drug and the liposomal formulation containing prodrug (HE liposome) manifested a higher sustained level of the latter, which was further improved in case of sphingomyelin-containing liposomes (STHE liposome). The pharmacokinetic parameters revealed an increase in half-life, from 61 min to 120 min for the HE liposomes and 296 min for the STHE liposomes. Therefore, increased entrapment was made possible through lipophilic derivatization, and it was subsequently tested in vivo.     

High-entrapment liposomes for 6-Mercaptopurine--a prodrug approach

Low entrapment of drugs into liposomes is a serious challenge in their commercial application. 6-Mercaptopurine (6-MP), an antineoplastic agent, is such a drug with low entrapment efficiency (EE). We devised their lipophilic derivatization as a means of enhancing EE by covalently coupling 6-MP with glyceryl monostearate (GMS) via a succinic anhydride spacer. This prodrug had an improved partition coefficient value of 25.16 compared to 1.22 for free drug, confirming higher lipophilicity. A hydrolysis rate study of prodrug indicated 2.90%, 12.5%, 24.1%, and 25.1% hydrolysis in phosphate buffered saline (PBS) (pH 7.4) and 10%, 20%, and 30% serum, respectively. Liposomes of phosphatidylcholine (PC)/sphingomyelin, cholesterol, and dicetyl phosphate bearing drug or prodrug were prepared by shaking by hand and sonication methods. The EE was found to increase from 1.92% for free drug to 91.8% for drug-conjugate. An in vitro cell line toxicity study on L1210 leukemia cells showed improved performance of liposome-encapsulated drug-conjugate compared to free drug. The plasma drug level profile following administration of free drug and the liposomal formulation containing prodrug (HE liposome) manifested a higher sustained level of the latter, which was further improved in case of sphingomyelin-containing liposomes (STHE liposome). The pharmacokinetic parameters revealed an increase in half-life, from 61 min to 120 min for the HE liposomes and 296 min for the STHE liposomes. Therefore, increased entrapment was made possible through lipophilic derivatization, and it was subsequently tested in vivo.     

Intradermal and follicular delivery of adapalene liposomes

Abstract

Background: Adapalene is a widely used topical anti-acne drug; however, it has many side effects. Liposomal drug delivery can play a major role by targeting delivery to pilosebaceous units, reducing side effects and offering better patient compliance.

Objective: To prepare and evaluate adapalene-encapsulated liposomes for their physiochemical and skin permeation properties.

Methods: A liposomal formulation of adapalene was prepared by the film hydration method and characterized for shape, size, polydispersity index (PDI), encapsulation efficiency and thermal behavior by techniques such as Zetasizer®, differential scanning calorimetry and transmission electron microscopy. Stability of the liposomes was evaluated for three months at different storage conditions. In vitro skin permeation studies and confocal laser microscopy were performed to evaluate adapalene permeation in pig ear skin and hair follicles.

Results: The optimized process and formulation parameters resulted in homogeneous population of liposomes with a diameter of 86.66?±?3.5?nm in diameter and encapsulation efficiency of 97.01?±?1.84% w/w. In vitro permeation studies indicated liposomal formulation delivered more drug (6.72?±?0.83?μg/cm²) in hair follicles than gel (3.33?±?0.26?μg/cm²) and drug solution (1.62?±?0.054?μg/cm²). Drug concentration delivered to the skin layers was also enhanced compared to other two formulations. Confocal microscopy images confirmed drug penetration in the hair follicles when delivered using the liposomal formulation.

Conclusion: Adapalene was efficiently encapsulated in liposomes and led to enhanced delivery in hair follicles, the desired target site for acne.     

Topical oleo-hydrogel preparation of ketoprofen with enhanced skin permeability.

In an attempt to improve the skin penetration of ketoprofen, various transdermal formulations were prepared, and their in vitro skin permeability and in vivo percutaneous absorption were evaluated. In vitro permeation studies were performed using a modified Franz cell diffusion system in which permeation parameters such as cumulative amount at 8 hr Q8hr, steady-state flux Jss, or lag time tL were determined. In the in vivo percutaneous absorption study using the hairless mouse, maximum concentration Cmax and area under the curve at 24 hr AUC24h were measured. The optimal transdermal formulation (oleo-hydrogel formulation) of ketoprofen showed a Q8hr value of 227.20 micrograms/cm2, a Jss value of 29.61 micrograms/cm2/hr, and a tL value of 0.46 hr. The Q8hr and Jss values were about 10-fold (p < .01) higher than those (Q8hr = 19.61 micrograms/cm2; Jss = 2.66 micrograms/cm2/hr) from the K-gel and about 3.5-fold (p < .01) than those (Q8hr = 60.00 micrograms/cm2; Jss = 7.99 micrograms/cm2/hr) of the K-plaster. In the in vivo percutaneous absorption, the Cmax (6.82 micrograms/ml) and AUC24h (55.74 micrograms.hr/ml) values of the optimal formulation were significantly (p < .01) higher than those of K-gel and K-plaster. The relative bioavailability of the oleo-hydrogel following transdermal administration in reference to oral administration was about 37%, and the Cmax value (4.73 micrograms/cm2) in the hypodermis following topical administration was much higher than those from the conventional products (Cmax of K-gel and K-plaster were 0.92 +/- 0.19 microgram/cm2 and 1.27 +/- 0.37 microgram/cm2, respectively). These data demonstrate that the oleo-hydrogel formulation of ketoprofen was more beneficial than conventional products (K-gel and K-plaster) in enhancing transdermal permeation and skin absorption of ketoprofen. Furthermore, there was a good correlation between in vitro permeation parameters and in vivo percutaneous absorption parameters.     

Development, characterization and in vitro evaluation of single or co-loaded imatinib mesylate liposomal formulations

Mitoxantrone-based combinations are a standard palliative treatment in hormone-refractory prostate cancer (HRPC) but with no survival benefit. Imatinib has shown preclinical activity against HRPC although minimal clinical therapeutic efficacy. Our previous in vitro studies demonstrated that simultaneous combination of imatinib with mitoxantrone yielded additive growth inhibition effects against PC-3 cell line. The main aim of the work was to develop novel liposomal formulations comprising imatinib co-encapsulated with mitoxantrone, by different loading methods and experimental conditions, in order to achieve the highest drug loading and maximum physical stability. In the optimized formulations, imatinib and mitoxantrone were actively co-loaded by means of a (NH4)2SO4 transmembrane gradient. Encapsulation efficiency, mean size diameter and drug retention in storage and in biological conditions were characterized. Our study presented for the first time an active loading method for imatinib and suggests that the optimized liposomal formulation co-encapsulates both drugs with high encapsulation efficiency (> 95%), shows enhanced drug retention under tested conditions and delivers a drug:drug ratio capable of improving tumor cell growth inhibition with a mitoxantrone dose reduction of 2.6-fold as compared to single liposomal formulation. Therefore, our nanotechnology-based drug combined platform may constitute a promising strategy in prostate cancer therapy.     

Preparation, characterization, and evaluation of liposomal ferulic acid in vitro and in vivo

In the present study, various gradients were evaluated for efficient loading of weak acid into liposomes. Several salt gradients showed efficient loading of ferulic acid (FA) into liposomes and the optimized conditions were established in calcium acetate gradient method to obtain 80.2 +/- 5.2% entrapment efficiency (EE). Unilamellar vesicles were observed in micrographs and liposomal FA showed good stability. 80% of FA was released from liposomes within 5 h in vitro. There is a novel finding in this study: that drugs could be entrapped with a high solubility in the intraliposomal buffer in contrast to the low solubility in the extraliposomal buffer. The results of body distribution in rats indicated that liposomes could improve the body distribution of FA. For FA liposome, the concentration of FA in brain was two-fold higher than that of free FA. Liposomal FA was a promising approach to improve the body distribution of FA.     

Preparation and characterization of lyophilised egg PC liposomes incorporating curcumin and evaluation of its activity against colorectal cancer cell lines

Curcumin has been associated with the treatment of various diseases in traditional medicine, among them cancer. The major problems that prevent its approval as therapeutic agent are its low water solubility and its relatively low in vivo bioavailability. Liposomes are considered as effective drug carriers because of their ability to solubilize hydrophobic compounds and to alter their pharmacokinetic properties. The purpose of this study was the development of lyophilised liposomal curcumin fully characterized in terms of its physical properties [(zeta-potential, size, size distribution and Polydispercity index (PI)], and to evaluate its in vitro cytotoxic against colorectal cancer cell lines in a short-term and in a long-term (clonogenic) assay. Curcumin was incorporated in egg-phosphatidylcholine (EPC) liposomes at a drug to lipid molar ratio 1:14 achieving high incorporation efficiency close to 85%. The liposomal curcumin was lyophilized preserving thus its stability. The reconstitution of the formulation resulted in the original liposomal suspension. The release in FBS showed a plateau near 14% at 96 hours of incubation. The in vitro studies against colorectal cancer cell lines have shown that liposomes improve the activity of curcumin especially in the long-term assay and the liposomal formulation found to be more potent against HCT116 and HCT15, cell lines which express the MDR phenotype. EPC liposomal curcumin in a molar ratio of curcumin/EPC 1:14 has shown improved cytotoxic activity versus free curcumin against colorectal cancer cell lines. In vivo studies based on the recent findings are in progress in our laboratory.     

Mucoadhesive nanoliposomal formulation for vaginal delivery of an antifungal

Context: Ciclopirox olamine (CPO) is indicated in the treatment of vaginal fungal infections. The frequent and large dosing of available vaginal CPO creams gives rise to poor compliance amongst females. In such a situation a delivery system capable of providing sustained release of CPO is warranted and can be realized through incorporation of its liposomal formulation into a mucoadhesive gel base. The liposomal formulation would offer sustained release whereas mucoadhesive gel would prolong the contact with vaginal wall; thus avoiding frequent and large dosing.

Objective: The present study aimed at investigating mucoadhesive liposomal CPO gel for vaginal use.

Method: The study embarked on evaluating liposomal CPO and its Carbopol 974^®P gel for stability at vaginal pH, release profile, rheological characteristics, mucoadhesive behavior and finally antifungal activity.

Results: The results revealed that CPO liposomes were stable at vaginal pH; its Carbopol gel released 58.75?±?6.4% of CPO at the end of 24?h which suggested sustained release. Rheology via viscometric, oscillatory stress sweep and oscillatory frequency sweep testing of the gel, studied at different temperatures and under different dilutions with vaginal fluid simulant testified pseudoplastic behavior of the gel. It also pointed towards the predominance of elastic behavior of the gel at all the dilutions. The gel exhibited good mucoadhesivity to sheep vaginal tissue. Furthermore, CPO entrapped in liposome too displayed antifungal activity.

Conclusion: The study undertaken recommended Carbopol 974^®P gel loaded with CPO liposomes as a potential delivery system for treatment of fungal vaginal infections.     

Topical Liposomal local Anesthetics: Design, Optimization and Evaluation of Formulations

To improve the rate of penetration into the skin, and to develop an effective topical anesthetic product, selected local anesthetic agents, benzocaine, lidocaine, dibucaine, etidocaine and tetracaine were encapsulated into liposomes using the solvent evaporation method. After the pilot experiments, tetracaine was selected for further development. Encapsulation efficiency was determined by centrifugation of liposomes and spectrophotometric analysis of liposome pellets and supernatants. Physical stability and organoleptic properties of the various liposomal tetracaine formulas were monitored visually and by microscopy for 1 year. Tetracaine was found to be suitable for the development of a liposomal drug delivery system with high encapsulation efficiency (60-90%) and physical stability. The results showed that encapsulation efficiency of tetracaine into liposomes can be increased by increasing drug concentration and pH, and including negatively charged stearic acid or unsaturated lipids in the formula. Stability of tetracaine increased with higher encapsulation efficiency, however the shelf life of the product was still short (2 months). In-process and finished product quality control parameters are suggested to facilitate the topical liposomal product development in general.     

Lactone stability and tissue distribution of free and liposomal encapsulated 9-nitrocamptothecin in rats following intravenous injection

9-Nitrocamptothecin (9-NC) is a newly developed but poorly soluble derivative of camptothecin (CPT), which has a wide spectrum of anticancer activity in preclinical evaluation. Lactone moiety is a key structural feature for the antitumor activity of CPT analogs including 9-NC. Lactone stability versus time profiles of 9-NC in vivo following intravenous (i.v.) administration of free and liposomal encapsulated 9-NC has been investigated in this article. After i.v. injection of 9-NC solution, it was found that lactone stability of 9-NC in liver was the poorest in vivo and even worse than that in plasma. In other tissues, lactone stability of 9-NC was better than that in plasma. After liposomal encapsulation, both lactone and total 9-NC concentrations in reticuloendothelial system (RES) tissues, for example, spleen, liver, and lung, were significantly increased. In particular, liposomal encapsulation had a significant improving effect on the lactone stability of 9-NC in the liver. The lactone percentage was increased from 39.11 +/- 16.93% to 65.57 +/- 9.73% (p < .05) at 10 min and from 30.99 +/- 6.54% to 51.22 +/- 11.10% (p < .01) at 30 min. On the basis of these results, a theoretical explanation of lactone stability in vivo was discussed. In summary, liposomal encapsulation, which resulted in passive targeting and a significant improvement of lactone stability in the liver, might have clinical utility.     

Oral sustained delivery of theophylline and cimetidine from in situ gelling pectin formulations in rabbits

The aim of this study was to evaluate the potential of an in situ gelling pectin formulation as a vehicle for the oral sustained delivery of theophylline and cimetidine. In vitro studies demonstrated diffusion-controlled release of theophylline from 1, 1.5, and 2% w/v pectin gels. Release of this drug from 1.5% w/v pectin gels formed in situ in rabbit stomach was sustained over a period of 12 hours giving a theophylline bioavailability some seven fold higher than when administered from a commercial syrup. In contrast, interactions between cimetidine and pectin led to weak gelation of the pectin sols that prevented any meaningful determination of in vitro release characteristics. Similarly, in vivo release profiles from pectin formulations containing cimetidine were similar to that from a solution of this drug in buffer, indicative of weak gelation. Examination of the content of the rabbit stomach 5 hours after administration of 1.5% w/v pectin sols containing drug confirmed gel formation, but gels containing cimetidine were noticeably softer than those containing theophylline.     

In vitro and in vivo anti-tumor effects of gemcitabine loaded with a new drug delivery system

In recent years, much attention has been given to liposomal formulation as an efficient drug loading system (DDS) in chemotherapy of cancer. In this study, the advantages of magnetic nanoparticles and Polyethylene Glyco (PEG) materials were considered to synthesize magnetic gemcitabine long-circulating liposomes (MGLL) and the potential of MGLL as a brand new delivery system was evaluated. MGLL was prepared using the reverse-phase evaporation method. In the optimized preparation, MGLL had an average diameter of 201 nm with a narrow size distribution measured by dynamic light scattering (DLS), which could be easily dispersed in ultrapure water under a stable state for 90 days. The encapsulation efficiency of gemcitabine in MGLL reached 87.2% as determined by HPLC. In vitro MTT assay showed that MGLL had significant cytotoxicity to MCF-7 cells compared with the conventional modalities. In vivo, the inhibition of tumor growth in MGLL group was more remarkable than that of other groups (P < 0.05). In conclusion, MGLL under optimized condition could be used as an effective carrier for tumor-targeted therapy.     

Development and evaluation of nanosized niosomal dispersion for oral delivery of Ganciclovir

Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the oral absorption and prolong the existence of the drug in the systemic circulation. So the purpose of the present study was to improve the oral bioavailability of Ganciclovir by preparing nanosized niosomal dispersion. Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of 1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal dispersions were characterized for entrapment efficiency, size, shape, in vitro drug release, release kinetic study, and in vivo performance. Optimized formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly high encapsulation of Ganciclovir (89±2.13%) with vesicle size of 144±3.47 nm (polydispersity index [PDI]=0.08). The in vitro release study signifies sustained release profile of niosomal dispersions. Release profile of prepared formulations have shown that more than 85.2±0.015% drug was released in 24 h with zero-order release kinetics. The results obtained also revealed that the types of surfactant and Cholesterol content ratio altered the entrapment efficiency, size, and drug release rate from niosomes. In vivo study on rats reveals five-time increment in bioavailability of Ganciclovir after oral administration of optimized formulation (NG8) as compared with tablet. The effective drug concentration (>0.69 μg/mL in plasma) was also maintained for at least 8 h on administration of the niosomal formulation. In conclusion, niosomes can be proposed as a potential oral delivery system for the effective delivery of Ganciclovir.