Development and characterization of 5-FU bearing ferritin appended solid lipid nanoparticles for tumour targeting

Ferritin coupled solid lipid nanoparticles were investigated for tumour targeting. Solid lipid nanoparticles were prepared using HSPC, cholesterol, DSPE and triolien. The SLNs without ferritin which has similar lipid composition were used for comparison. SLNs preparations were characterized for shape, size and percentage entrapment. The average size of SLNs was found to be in the range 110-152 nm and maximum drug entrapment was found to be 34.6-39.1%. In vitro drug release from the formulations is obeying fickian release kinetics. Cellular uptake and IC(50) values of the formulation were determined in vitro in MDA-MB-468 breast cancer cells. In vitro cell binding of Fr-SLN exhibits 7.7-folds higher binding to MDA-MB-468 breast cancer cells in comparison to plain SLNs. Ex-vivo cytotoxicity assay on targeted nanoparticles gave IC(50) of 1.28 microM and non-targeted nanoparticles gave IC(50) of 3.56 microM. In therapeutic experiments, 5-FU, SLNs and Fr-SLNs were administered at the dose of 10 mg 5-FU/kg body weight to MDA-MB-468 tumour bearing Balb/c mice. Administration of Fr-SLNs formulation results in effective reduction in tumour growth as compared with free 5-FU and plain SLNs. The result demonstrates that this delivery system possessed an enhanced anti-tumour activity. The results warrant further evaluation of this delivery system.     

In vitro and ex vivo toxicological testing of sildenafil-loaded solid lipid nanoparticles

Abstract

The aim of this study was to investigate the potential cytotoxicity of solid lipid nanoparticles (SLN) loaded with sildenafil. The SLNs were tested as a new drug delivery system (DDS) for the inhalable treatment of pulmonary hypertension in human lungs. Solubility of sildenafil in SLN lipid matrix (30:70 phospholipid:triglyceride) was determined to 1% sildenafil base and 0.1% sildenafil citrate, respectively. Sildenafil-loaded SLN with particle size of approximately 180?nm and monomodal particle size distribution were successfully manufactured using a novel microchannel homogenization method and were stable up to three months. Sildenafil-loaded SLN were then used in in vitro and ex vivo models representing lung and heart tissue. For in vitro models, human alveolar epithelial cell line (A459) and mouse heart endothelium cell line (MHEC5-T) were used. For ex vivo models, rat precision cut lung slices (PCLS) and rat heart slices (PCHS) were used. All the models were treated with plain SLN and sildenafil-loaded SLN in a concentration range of 0–5000?µg/ml of lipid matrix. The toxicity was evaluated in vitro and ex vivo by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Median lethal dose 50% (LD₅₀) values for A549 cells and PCLS were found to be in the range of 1200–1900?µg/ml while for MHEC5-T cells and precision cut heart slices values were found between 1500 and 2800?µg/ml. PCHS showed slightly higher LD₅₀ values in comparison to PCLS. Considering the toxicological aspects, sildenafil-loaded SLN could have potential in the treatment of pulmonary hypertension via inhalation route.     

Preparation and passive target of 5-fluorouracil solid lipid nanoparticles

This work studied the intravenous injection formulation of solid lipid nanoparticles (SLNs) loaded with 5-fluorouracil (5-FU). The goal was to design longer drug residence in vivo and passive targeting nanoparticles which could improve therapeutic efficacy and reduce side-effects. Based on the optimized results of uniform design experiment, 5-FU-SLNs were prepared by multiple emulsion-ultrasonication (w/o/w). The SLNs were found to be relatively uniform in size (182.1?±?25.8?nm) with a negative zeta potential (?27.89?±?5.1 mV). The average drug entrapment efficiency and loading were 74% and 10%, respectively. Compared with the 5-FU solution (t_1/2β, 0.593h; MRT, 0.358h) after intravenous injection to rats, the pharmacokinetic parameters of 5-FU-SLNs exhibited a longer retention time. (t_1/2β, 4.0628h; MRT, 3.5321h). The area under curve of plasma concentration-time (AUC) of 5-FU-SLNs was 1.48 times greater than that of free drugs. The overall targeting efficiency (TE^C) of the 5-FU-SLNs was enhanced from 13.25–20.45% in the lung and from 11.48–23.16% in kidney while the spleen distribution of 5-FU was significantly reduced as compared with that of the 5-FU solution. These results indicated that 5-FU-SLNs were promising passive targeting therapeutic agents for curing primary lung carcinoma.     

Galactosylated solid lipid nanoparticles with cucurbitacin B improves the liver targetability

This study intended to prepare liver-targeting solid lipid nanoparticles (SLNs) with a hepatoprotective drug, cucurbitacin B (Cuc B), using a galactosylated lipid, N-hexadecyl lactobionamide (N-HLBA). The galactosyl-lipid N-HLBA was prepared via the lactone form intermediates of lactobionic acid and synthesized by anchoring galactose to hexadecylamine lipid. The Cuc B-loaded galactosylated and conventional SLNs were successfully prepared by a high-pressure homogenization method. The two SLNs showed similar physical and pharmaceutical properties, including: the particle size measured by laser diffraction was 135?nm for galactosylated SLN (GalSLN) and 123?nm for conventional SLNs (CSLN); zeta potentials were ?31.6 mV (GalSLN) and ?34.3 mV(CSLN); in vitro release behavior of the two SLNs was similar, and both showed the biphasic drug release pattern with burst release at the initial stage and prolonged release afterwards. In contrast, the two SLNs demonstrated a marked difference in in vitro cellular cytotoxicity and in vivo tissue distribution performances. The IC₅₀ values of Cuc B in the two SLNs were by far lower than those of Cuc B solution and further Cuc B-GalSLN had about half the IC₅₀ value of Cuc B-CSLN. These results indicated that the encapsulation of Cuc B in SLNs resulted in the enhancement of cytotoxic activity, and galactosyl ligand could further enhance the cellular accumulation and cytotoxicity of Cuc B. The weighted-average overall drug targeting efficiency (Te) was used to evaluate the liver targetability. Cuc B-GalSLN gave a relatively high (Te)_liver value of 63.6%, ～ 2.5-times greater than that of Cuc B-CSLN (25.3%) and Cuc B solution (23.8%). In summary, the incorporation of N-HLBA into SLNs significantly enhanced the liver targetability of Cuc B-loaded SLNs and GalSLN had a great potential as a drug delivery carrier for improved liver targetability.     

Physico-chemical characterisation,cytotoxic activity,and biocompatibility studies of tamoxifen-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification method

Abstract

Context: Solid lipid nanoparticles (SLNs) can efficiently and efficaciously incorporate anti-cancer agents. Objective: To prepare and characterise tamoxifen (TAM)-loaded SLNs. Materials and methods: Glyceryl monostearate, Tween-80, and trehalose were used in SLNs. SLNs were tested via dynamic light scattering (DLS), transmission electron microscopy (TEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Results: Characterisation studies revealed SLNs of about 540 nm with a negative surface charge and confirmed the entrapment of TAM in the SLNs. The entrapment efficiency was estimated to be 60%. Discussion: The in vitro drug release profile demonstrated a gradual increase followed by a release plateau for several days. A drug concentration-dependent increase in cytotoxic activity was observed when the SLNs were evaluated in cell cultures. Conclusion: Biocompatible and stable lyophilised SLNs were successfully prepared and found to possess properties that may be utilised in an anti-cancer drug delivery system.     

Solid lipid nanoparticles of diethylcarbamazine citrate for enhanced delivery to the lymphatics: in vitro and in vivo evaluation

Objectives: The major objective is to target diethylcarbamazine citrate (DEC) to the lymphatics and to increase its retention time. The effect of various excipients on the physicochemical characteristics of the nanoparticles was also studied.

Materials and methods: Solid lipid nanoparticles (SLNs) of DEC were prepared by ultrasonication by varying the concentrations of compritol 888 ATO, poloxamer 188 and soya lecithin. The SLNs were evaluated for size, shape, texture, surface charge, physical nature of the entrapped drug, entrapment efficiency and in vitro drug release. In vivo animal studies were carried out to estimate the pharmacokinetic parameters in blood and drug concentration in lymph after oral administration.

Results: The size of the spherical particles was in the range of 27.25 ± 3.43 nm to 179 ± 3.08 nm and a maximum entrapment efficiency of 68.63 ± 1.53% was observed. In vitro release studies in pH 7.4 PBS displayed a rapid release and the maximum time taken for the complete drug to release was 150 min. In vivo studies indicated an enhancement in the amount of drug that reached lymphatics when administered via SLNs.

Conclusion: Targeting of DEC to the lymphatics is possible through SLNs and the retention time in the lymphatics can also be enhanced.     

Solid lipid nanoparticles for transdermal delivery of diclofenac sodium: preparation,characterization and in vitro studies

The aim of this study was to prepare diclofenac sodium (DNa) solid lipid nanoparticles (SLNs) by a modified emulsion/solvent evaporation method for transdermal delivery. Five independent processing parameters including the lipid matrix, emulsifiers, co-emulsifiers, water-dispersed phase and organic phase were assessed systematically to enhance the entrapment of DNa. The SLNs produced by optimal formulation were submicrometre size with low polydispersity index, the entrapment efficiency was about 89% and the drug loading was about 9.5%. Shape and surface morphology were determined by transmission electron microscopy, which revealed the fairly spherical and core-shell shapes of the SLNs. The in vitro release of SLNs showed a two-step release pattern: one initial burst release followed by a second slow-release phase. In the in vitro cutaneous permeation studies, value of flux obtained for DNa solution was higher than that of SLNs suspension. SLNs had also been shown to improve the dermal localization of DNa.     

Using doxorubicin and siRNA-loaded heptapeptide-conjugated nanoparticles to enhance chemosensitization in epidermal growth factor receptor high-expressed breast cancer cells

Abstract

The aim of this study was to develop the heptapeptide-conjugated active targeting nanoparticles for delivery of doxorubicin and siRNA to epidermal growth factor receptor (EGFR) high-expressed breast cancer cells. The active targeting nanoparticles were prepared by using a synthesized poly(D,L-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with a heptapeptide. The particle size of peptide-conjugated nanoparticles was less than 200?nm with narrow size distribution and the surface charge was negative. The uptake of peptide-conjugated nanoparticles was more efficient in EGFR high-expressed MDA-MB-468 cells than in EGFR low-expressed HepG2 cells by 3.9 folds due to peptide specific binding to EGF receptor followed by EGF receptor-mediated endocytosis. The nanoparticles were used to deliver doxorubicin and siRNA, and their in vitro release was faster in pH 4.0 (500?U lipase) than in pH 7.4. The IC₅₀ of doxorubicin-loaded peptide-conjugated nanoparticles was lower than that of peptide-free nanoparticles by 2.3 folds in MDA-MB-468 cells. Similarly, the cellular growth inhibition of siRNA/DOTAP-loaded peptide-conjugated nanoparticles was 2.1 folds higher than that of peptide-free nanoparticles. In conclusion, the heptapeptide-conjugated PLGA-PEG nanoparticles provided active targeting potential to EGFR high-expressed MDA-MB-468 breast cancer cells, and a synergistic cytotoxicity effect was achieved by co-delivery of doxorubicin and siRNA/DOTAP-loaded peptide-conjugated nanoparticles.     

Nanostructured lipid carriers,solid lipid nanoparticles,and polymeric nanoparticles: which kind of drug delivery system is better for glioblastoma chemotherapy?

Context: Glioblastoma is a malignant brain tumor originating in the central nervous system. Successfully therapy of this disease required the efficient delivery of therapeutic agents to the tumor cells and tissues. Delivery of anticancer drugs using novel nanocarriers is promising in glioma treatment.

Objective: Polymeric nanoparticles (PNPs), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs) were constructed for the delivery of temozolomide (TMZ). The anti-tumor effects of the three kinds of nanocarriers were compared to provide the optimum choice for gliomatosis cerebri treatment.

Methods: TMZ-loaded PNPs (T-PNPs), SLNs (T-SLNs), and NLCs (T-NLCs) were formulated. Their particle size, zeta potential, drug encapsulation efficiency (EE), and drug loading (DL) capacity were evaluated. Anti-tumor efficacies of the three kinds of nanocarriers were evaluated on U87 malignant glioma cells (U87?MG cells) and mice-bearing malignant glioma model.

Results: T-NLCs displayed the best anti-tumor activity than other formulations in vivo and in vitro. The most significantly glioma inhibition was observed on NLCs formulations than PNPs and SLNs.

Conclusion: This work demonstrates that NLCs can deliver TMZ into U87MG cells more efficiently, with higher inhibition efficacy than PNPs and SLNs. T-NLCs could be an excellent drug delivery system for glioblastoma chemotherapy.     

Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles

Abstract

The incorporation of a high percentage of targeting molecules into drug delivery system is one of the important methods for improving efficacy of targeting therapeutic drugs to cancer cells. PLGA-based drug delivery carriers with folic acid (FA) as targeting molecule have a low targeting efficiency due to a low FA conjugation ratio. In this work, we fabricated a FA-conjugated PLGA system using a crosslinker 1, 3-diaminopropane and have achieved a high conjugation ratio of 46.7% (mol/mol). The as-prepared PLGA-based biomaterial was used to encapsulate therapeutic drug 5-fluorouracil (5-FU) into nanoparticles. In the in vitro experiments, an IC₅₀ of 5.69?µg/mL has been achieved for 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles on HT-29 cancer cells and is significantly lower than that of 5-FU and 5-FU loaded PLGA nanoparticles which only have an IC₅₀ of 22.9 and 14.17?µg/mL, respectively. The fluorescent microscopy images showed that nanoparticles with FA are largely taken up by HT-29 cancer cells and the targeting nanoparticles have more affinity to cancer cells than the pure drugs and untreated nanoparticles. Therefore, the 1, 3-diaminopropane can facilitate the conjugation of FA to PLGA to form a novel polymer and 5-FU loaded PLGA-1, 3-diaminopropane-folic acid nanoparticles can be a highly efficient system for specific delivery of drugs to cancer cells.     

Development and characterization of itraconazole-loaded solid lipid nanoparticles for ocular delivery

Abstract

The purpose of this study was to investigate the feasibility of entrapping water-insoluble drug itraconazole into solid lipid nanoparticles (SLNs) for topical ocular delivery. The drug-loaded SLNs were prepared from stearic acid and palmitic acid using different concentrations of polyvinyl alcohol employed as emulsifier. SLNs were prepared by the melt-emulsion sonication and low temperature-solidification method and characterized for particle size, zeta potential, drug loading and drug entrapment efficiency. The mean particle size of SLNs prepared with stearic acid ranged from 139 to 199?nm, while the SLNs prepared with palmitic acid had particle size in the range of 126–160?nm. The SLNs were spherical in shape. Stearic acid-SLNs showed higher entrapment of drug compared with palmitic acid-SLNs. Differential scanning calorimetry (DSC) and X-ray diffraction measurements showed decrease in crystallinity of drug in the SLN formulations. The modified Franz-diffusion cell and freshly excised goat corneas were used to test drug corneal permeability. Permeation of itraconazole from stearic acid-SLNs was higher than that obtained with palmitic acid-SLNs. The SLNs showed clear zone of inhibition against Aspergillus flavus indicating antimicrobial efficacy of formulations.     

Clinical comparative study of optimized metronidazole loaded lipid nanocarrier vaginal emulgel for management of bacterial vaginosis and its recurrence

The main focus of the current work was to design, evaluate and clinically compare the efficiency of novel metronidazole (MTD) loaded solid lipid nanoparticles (SLNs) vaginal emulgel with the marketed vaginal gel (Metron^®) against Bacterial vaginosis (BV). Eight formulations were fabricated using 2³ full factorial design and prepared by stearic acid and tween 80 as solid lipid and surfactant, respectively. Lipid and surfactant concentrations in addition to sonication amplitude were chosen as the independent variables (X₁–X₃). Then, the prepared MTD loaded SLNs were evaluated based on the dependent variables which were particle size, polydispersity index, zeta potential, entrapment efficiency, and cumulative % drug release for 24 h (Y₁–Y₅). The in vitro release study exhibited a sustained release of MTD from the SLNs up to 24 h. The optimal MTD loaded SLNs showed nanosized particles (256 nm) with EE% (52%), and an acceptable ZP value (−29.5 mV). Also, the optimized MTD-SLNs formulation was incorporated into Carbopol emulgel and investigated clinically for its effect against BV. Clinical studies recorded significant enhancement in therapeutic response of MTD from optimized SLNs vaginal emulgel formulation regarding the clinical treatment (p < .05) and low recurrence rate (p < .001) against the marketed product. In conclusion, our findings recommend that the fabricated MTD loaded SLNs vaginal emulgel have significant therapeutic effect in terms of BV management over commercially obtainable marketed vaginal gel (Metron^®).     

Double-effective chitosan scaffold-PLGA nanoparticle system for brain tumour therapy: in vitro study

Abstract

The chitosan scaffold, which has both of anticancer and antivascularization effects, was developed for using in local therapy of brain tumours. This is why, poly-lactic-co-glycolic acid (50:50) nanoparticles (～200?nm) including an anticancer drug, 5-fluorouracil (5-FU), were prepared by emulsion-solvent evaporation method. Then, these nanoparticles and antivascularization agent, bevacizumab, were loaded into the scaffold during manufacturing by freeze-drying and embedding after freeze-drying, respectively. The idea behind this system is to destroy tumour tissue by releasing 5-FU and to prevent the proliferation of tumour cells by releasing bevacizumab. In addition, 3D scaffold can support healthy tissue formation in the tumourigenic region. In vitro effectiveness of this system was investigated on T98G human glioblastoma cell line and human umbilical vein endothelial cells. The results show that the chitosan scaffold containing 100?µg 5-FU and 100?µg bevacizumab has a potential to prevent the tumour formation in vitro conditions.     

Nanostructured lipid carriers (NLCs) versus solid lipid nanoparticles (SLNs) for topical delivery of meloxicam

Abstract

Objective: The aim of this study was to develop nanostructured lipid carriers (NLCs) as well as solid lipid nanoparticles (SLNs) and evaluate their potential in the topical delivery of meloxicam (MLX).

Materials and methods: The effect of various compositional variations on their physicochemical properties was investigated. Furthermore, MLX-loaded lipid nanoparticles-based hydrogels were formulated and the gels were evaluated as vehicles for topical application.

Results and discussion: The results showed that NLC and SLN dispersions had spherical shapes with an average size between 215 and 430?nm. High entrapment efficiency was obtained ranging from 61.94 to 90.38% with negatively charged zeta potential in the range of ?19.1 to ?25.7?mV. The release profiles of all formulations exhibited sustained release characteristics over 48?h and the release rates increased as the amount of liquid lipid in lipid core increased. Finally, Precirol NLC with 50% Miglyol® 812 and its corresponding SLN were incorporated in hydrogels. The gels showed adequate pH, non-Newtonian flow with shear-thinning behavior and controlled release profiles. The biological evaluation revealed that MLX-loaded NLC gel showed more pronounced effect compared to MLX-loaded SLN gel.

Conclusion: It can be concluded that lipid nanoparticles represent promising particulate carriers for topical application.     

Lipid nanoparticles for chemotherapeutic applications: strategies to improve anticancer efficacy

Introduction: Chemotherapy remains the major form of treatment for cancer. However, chemotherapy often fails due to a variety of barriers, resulting in a limited intratumoral drug disposition. Recently, lipid nanoparticles (LNs, i.e., solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs)) have been shown to provide a favorable means for efficiently delivering drugs to tumor sites, while minimizing their side effects.

Areas covered: The delivery of drugs to tumors is restricted by a series of barriers, including the tumor abnormalities, strong adverse effects and poor specificity of cytotoxic drugs, and the induction of multidrug resistance (MDR). The present review summarizes the strategies using SLNs and/or NLCs to improve the anticancer efficacy of cytotoxic drugs, including passive targeting, active targeting, long circulating and MDR reversing. Specifically, the most significant in vitro and in vivo results on the use of SLNs and/or NLCs are highlighted.

Expert opinion: The future success of SLNs and NLCs for administration of cytotoxic drugs will depend on their ability to efficiently encapsulate and release drugs, the possibility for large-scale production, selective tumor cells targeting and increased antitumor efficacy with reduced tissue toxicity.     

Fabrication and Evaluation of Curcumin-loaded Nanoparticles Based on Solid Lipid as a New Type of Colloidal Drug Delivery System

Curcumin has very broad spectrum of biological activities; however, photodegradation, short half-life and low bioavailability have limited its clinical application. Curcumin-loaded solid lipid nanoparticles were studied to overcome these problems. The aim of this study was to optimize the best formulation on curcumin-loaded solid lipid nanoparticles. Emulsion-evaporation and low temperature-solidification technique was applied with monostearin as lipid carriers. The single factor analysis and orthogonal design were used to optimize formulation and various parameters were investigate. By the optimisation of a single factor analysis and orthogonal test, the particles size, polydispersity index, zeta potential, encapsulation efficiency and drug loading capacity of the optimised formulation were 99.99 nm, 0.158, −19.9 mV, 97.86%, and 4.35%, respectively. The differential scanning calorimetry and X-ray diffraction analysis results demonstrated new structure was formed in nanoparticles. The release kinetics in vitro demonstrated curcumin-loaded solid lipid nanoparticles can control drug release. These studies confirmed that curcumin-loaded solid lipid nanoparticles could be prepared successfully with high drug entrapment efficiency and loading capacity. Curcumin-loaded solid lipid nanoparticles may be a promising drug delivery system to control drug release and improve bioavailability.     

Breast cancer targeted chemotherapy based on doxorubicin-loaded bombesin peptide modified nanocarriers

Context: Breast cancer is the most common cancer in female population. Breast cancer chemotherapy using doxorubicin (DOX) is well illustrated. However, a significant obstacle for successful chemotherapy with DOX is multidrug resistant (MDR) in breast cancer cells. Targeted nanocarriers have emerged as frontier research for the improvement of cancer chemotherapy.

Objective: Bombesin (Bn)-modified, DOX-loaded solid lipid nanoparticles (Bn-DOX/SLNs) were constructed. Doxorubicin-resistant MCF-7/MDR human breast cancer cells and the cancer animal models were applied for the evaluation of the in vitro and in vivo anti-tumor effect of Bn-DOX/SLNs.

Methods: Bn-conjugated lipids were synthesized. DOX was then loaded into Bn-modified SLNs. The physicochemical properties of the Bn-DOX/SLNs were investigated by particle size and zeta potential measurement, drug loading and drug-entrapment efficiency, and in vitro drug release behavior. In vitro cytotoxicity against MCF-7/MDR cells was investigated, and in vivo anti-tumor of SLNs was evaluated in human breast cancer mice models.

Results: Bn-DOX/SLNs showed an excellent in vitro cytotoxicity and in vivo anti-tumor effect both in MCF-7/MDR breast cancer cells and breast cancer animal model.

Conclusion: The results demonstrated that Bn-DOX/SLNs reversed the resistance of doxorubicin, suggesting that chemotherapy using this kind of targeted nanocarriers may benefit human breast MDR cancer therapy.     

Fluconazole-loaded solid lipid nanoparticles topical gel for treatment of pityriasis versicolor: formulation and clinical study

Solid lipid nanoparticles (SLNs) are very potential formulations for topical delivery of antifungal drugs. Hence, the purpose of this research was to formulate the well-known antifungal agent Fluconazole (FLZ)-loaded SLNs topical gel to improve its efficiency for treatment of Pityriasis Versicolor (PV). FLZ-SLNs were prepared by modified high shear homogenization and ultrasonication method using different concentration of solid lipid (Compritol 888 ATO, Precirol ATO5) and surfactant (Cremophor RH40, Poloxamer 407). The physicochemical properties and the in vitro release study for all FLZ-SLNs were investigated. Furthermore, the optimized FLZ-SLN formula was incorporated into gel using Carpobol 934. A randomized controlled clinical trial (RCT) of potential batches was carried out on 30 well diagnosed PV patients comparing to market product Candistan^® 1% cream. Follow up was done for 4?weeks by clinical and KOH examinations. The results showed that FlZ-SLNs were almost spherical shape having colloidal sizes with no aggregation. The drug entrapment efficiency ranged from 55.49% to 83.04%. The zeta potential values lie between ?21 and ?33?mV presenting good stability. FLZ showed prolonged in vitro release from SLNs dispersion and its Carbapol gel following Higuchi order equation. Clinical studies registered significant improvement (p?® cream.     

Exploring dendrimer towards dual drug delivery: pH responsive simultaneous drug-release kinetics

A major problem associated with conventional leukaemia chemotherapy is the development of resistance that can be surmounted well by combination chemotherapy. The objective of the present investigation is to report a novel technology to load two anti-leukaemic drugs of choice simultaneously inside the PAMAM dendrimer. Under optimized conditions of pH and dialysis time, one molecule of PAMAM dendrimer was found to be capable of entrapping 27.02 ± 0.51 and 8.00 ± 0.46 molecules of Methotrexate and all-trans Retinoic acid (ATRA), respectively. The simultaneous in-vitro release profiling of the loaded drugs was studied at pH 4, 7.4 and 10. The release kinetics was found to be governed by degree of dendrimer protonation, with more sustained and controlled behaviour at pH 7.4. Terminal loading of dendrimer with less haemolytic bioactive (ATRA) reduced the haemolytic toxicity of the dendrimer formulation. A cytotoxicity study was performed on HeLa cell lines by MTT assay, wherein after 72 h, the dual-drug loaded dendrimer was found to be more efficient (IC₅₀ 0.5 µM) as compared to that of the free drug combination (IC₅₀ 0.75 µM).     

Evaluation of hypericin-loaded solid lipid nanoparticles: Physicochemical properties,photostability and phototoxicity

Hypericin (HYP), a natural photosensitizer, has powerful photo-oxidizing ability, tumor-seeking characteristics, and minimal dark toxicity; nevertheless, it has proven high lipid solubility compared to its sparingly water soluble nature. Therefore, its formulation into solid lipid nanoparticles (SLNs) has attracted increasing attention as a potential drug-delivery carrier. Two HYP-loaded SLNs formulations were prepared utilizing microemulsion-based technique. Thereafter, the physicochemical properties of the formulations were investigated and evaluated. HYP-loaded SLNs showed spherical shape with mean particle size ranging from 200–300?nm for both formulations (FA and FB). The encapsulation efficiencies reached above 80% and FA showed significant higher encapsulation than FB (P?<?0.05), also, the thermal analysis using differential scanning calorimetry (DSC) indicated good compatibility between hypericin and lipids forming the cores in both formulations. Spectroscopic measurements of the photostability study showed that hypericin encapsulation into SLNs improved its photostability, compared to free HYP in 0.1% ethanolic solution. However, photocytotoxicity studies on HepG2 cells revealed an evident inhibition of the photodynamic efficacy of HYP-loaded SLNs, compared to free HYP. In conclusion, although the elevated entrapment efficiency of HYP into SLNs increased its photostability, it decreased its phototoxicity which might be due to the quenching deactivation of HYP molecules resulting from SLN compactness and thickness structure.