Development of artemether and lumefantrine co-loaded nanostructured lipid carriers: physicochemical characterization and in vivo antimalarial activity

Context: Artemether and lumefantrine combination therapy is well-accepted for uncomplicated malaria treatment. However, the current available formulation has several pharmacokinetic mismatches such as drug degradation in gastrointestinal tract, erratic absorption, etc. Hence, need of the hour is the injectable formulation, which can overcome the pharmacokinetic mismatch associated with current available formulation in the market.

Objective: To fabricate artemether and lumefantrine co-loaded injectable nanostructured lipid carriers (NLCs) formulation.

Materials and methods: Artemether and lumefantrine co-loaded NLCs were fabricated using homogenization followed by ultra-sonication method. Fabricated NLCs were evalauated for their physicochemical characteristics, and suitability of the formulation for malaria treatment was evaluated using in vivo animal model (Plasmodium berghei-infected mice).

Results, discussion and conclusion: Artemether and lumefantrine co-loaded NLCs had a hydrodynamic diameter of ～145?nm with the surface charge of ?66?mV. Due to the lipophilic nature of both antimalarial drugs, both single drugs-loaded and co-loaded NLCs have shown high encapsulation efficiency, which is 84% for artemether and 79% for lumefantrine. In vitro drug release study has shown a biphasic drug release pattern, which has shown 63% artemether release and 45% of lumefantrine release over a time period of 30?h. Plasmodium berghei-infected mice treated with artemether and lumefantrine co-loaded NLCs showed better antimalarial activity with respect to parasitemia progression and survivability period.     

Drug targeting to arthritic region via folic acid appended surface-engineered multi-walled carbon nanotubes

This study was aimed at developing and investigating folate anchored carbon nanotubes for targeting an anti-arthritic drug, Methotrexate (MTX) to inflammatory arthritic region. The folic acid (FA) was conjugated to amidated multi-walled carbon nanotubes (MWCNTs) and confirmed by Fourier transform infrared (FTIR), ¹H NMR spectroscopy and X-ray diffraction analysis. The MTX was loaded into the pristine and functionalized-MWCNTs and extensively characterized in vitro and in vivo studies. The drug entrapment efficiency was found high in folate conjugated MWCNTs. In vitro drug release in PBS (pH 7.4) from pristine MWCNTs and folate conjugated MWCNTs formulation was found to be 66.35?±?2.3 and 56.88?±?1.9% in 24?h, respectively. Folate conjugated MWCNTs significantly increased (p?<?0.005) the percentage inhibition of arthritis, biological half-life and volume of distribution of MTX as compared to MTX-loaded naked MWCNTs as well as free MTX. In in vivo biodistribution studies, MTX was found to be significantly higher (p?<?0.005) in arthritic joints from folate functionalized MWCNTs as compared to free drug as well as drug-loaded naked MWCNTs. The present outcomes highlights the propensity of drug-loaded functionalized MWCNTs to alter the pharmacokinetics as well as sustained and targeted drug delivery system as well.     

Targeted delivery of etoposide to cancer cells by folate-modified nanostructured lipid drug delivery system

Abstract

Context: Cardiotoxicity and myelosuppression of etoposide (ETP) limited its clinical application. Targeted drug delivery system could deliver anticancer agents to the target cancerous cells, thus reducing their toxicity.

Objective: In this study, folate (FA) was applied for the construction of nanostructured lipid carriers (NLCs), and used for targeted delivery of ETP to tumors overexpresses the FA receptors.

Methods: FA-poly (ethylene glycol)-distearoylphosphatidylethanolamine was synthesized. FA decorated and ETP-loaded NLCs (FA-ETP-NLCs) were prepared and the formulation was optimized by Box–Behnken design. Their particle size (PS), zeta potential and drug encapsulation efficiency (EE) was evaluated. In vitro cytotoxicity studies of FA-ETP-NLCs were tested in CT26, SGC7901, NCI-H209 cell lines. In vivo antitumor efficacies of the carriers were evaluated on mice bearing CT26 cells xenografts.

Results: The optimum FA-ETP-NLCs formulations had a PS of 120.86?nm. The growth of CT26, SGC790 or NCI-H209 cells in vitro was obviously inhibited. FA-ETP-NLCs also displayed the best antitumor activity than other formulations in vivo.

Conclusion: The results demonstrated that FA-ETP-NLCs were efficient in selective delivery to CT26, SGC790 or NCI-H209 cells overexpressing the FA receptors. Also, FA-ETP-NLCs can sufficiently transfer ETP to the cancer cells, enhance the antitumor capacity. Thus, FA-ETP-NLCs could prove to be a superior nanomedicine to achieve tumor therapeutic efficacy.     

Preparation and characterization of methotrexate-loaded microcapsules

Abstract

Methotrexate (MTX) has toxic effect to healthy tissues. Microencapsulation coats particles with a functional coat to optimize storage stability and to modulate release. In the present study, a new MTX encapsulated microcapsules were synthesized for controlling MTX release. Controlled drug release provides releasing of efficient dose and prevent drug side effect to tissues and also protects MTX from oxygen, pH and other interactions. MTX was encapsulated through biocompatible hyaluronic acid (HA) and sodium alginate (SA) with an encapsulation system to reduce its toxicity and for controlled release. The microcapsules prepared by vibrating nozzle were cross-linked with SA, HA and calcium chloride. Nozzle diameter and MTX concentration were changed according to loaded MTX and encapsulation efficiency were determined using HPLC. For the reliability of the data, validation studies of the HPLC method were performed. The precision of the method was demonstrated using intra- and inter-day assay relative standard deviation (RSD) values which are less than 2% in all instances. For the characterization of microcapsules, particle size, drug loading and in vitro drug release studies were performed. Diameters of MTX-loaded microcapsules were acquired approximately 160, 400 and 800?µm. Surface morphology of encapsulated microcapsules were displayed with light microscope. Eighty-nine percent MTX encapsulation efficiencies were achieved. Encapsulated MTX microcapsules showed controlled release when compared to pure MTX. While powder MTX dissolved completely in 10?min in the dissolution medium, MTX release from encapsulated MTX microcapsules became 40?h in 0.1?M PBS pH 7.4, including NaCl. MTX release from MTX-loaded microcapsules was reached to 79%. Moreover, drug efficiency was examined in vitro cell culture tests. Viability of 5RP7 cells were decreased to 88.5% for 96?h. When MTX was given directly to 5RP7 cells, viability of 5RP7 cells was decreased to 49.7% for 96?h. Flow cytometry studies also showed that, MTX microcapsules induced apoptosis. The goal of this study is to provide controlled release of MTX and to reduce the toxic effect of MTX.     

Synthesis,characterization, and kinetic release study of methotrexate loaded mPEG–PCL polymersomes for inhibition of MCF-7 breast cancer cell line

In this study, we designed a polymersome system for the controlled release of methotrexate (MTX) as an anticancer drug with the objective of improving the loading efficiency of the drug in polymersomes as well as achievement of an efficient control on the release rate of drug from nanocarriers. We synthesized mono methoxy poly(ethylene glycol)–poly(e-caprolactone) (mPEG–PCL) diblock copolymers. The structure of the copolymers was characterized by proton nuclear magnetic resonance spectroscopy (¹H NMR), Fourier transform infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC) techniques. MTX was encapsulated within nanoparticles (NPs) through multiple emulsion method. The resulting NPs were characterized further by various techniques such as atomic force microscopy (AFM) and dynamic light scattering (DLS). Next, the various kinetic equations were fitted to the release data of MTX from MTX-loaded mPEG–PCL polymersomes. The results showed that the zeta potential of MTX-loaded mPEG–PCL polymersomes was about –5.49?mV and the average size was 49.18?nm. MTX was encapsulated into polymersomes loading capacity of 12?±?0.09% and encapsulation efficiency of 45.5?±?0.41%. The metabolic activity assays of void of MTX, mPEG–PCL polymersomes, and MTX-loaded mPEG–PCL polymersomes were compared to each other by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of the treated MCF-7 cell lines. It can be concluded that application of NPs is a better and more effective strategy for controlled and slow release of MTX in the treatment of cancer.     

Optimization of nanostructured lipid carriers of lamotrigine for brain delivery: in vitro characterization and in vivo efficacy in epilepsy

Objective: The aim of the present work was to investigate the efficacy of nanostructured lipid carriers (NLCs) to enhance the brain targeting of lamotrigine (LMT) following intranasal (IN) administration.

Methods: Formulation was optimized using four-factor three levels Box– Behnken design to establish the functional relationships between variables on responses, that is, particle size, entrapment efficiency (EE) and percentage cumulative drug release of LMT-loaded NLCs. NLCs were evaluated for particle size, surface morphology, %EE and in vitro release and ex vivo permeation. The developed formulation was subjected to stability study, in vivo efficacy and scintigraphic study in Wistar rat model.

Results: The NLCs had a mean particle size of 151.6 ± 7.6 nm, polydispersity index of 0.249 ± 0.035, zeta potential of 11.75 ± 2.96 mV and EE of 96.64 ± 4.27%. The drug release from NLCs followed Fickian diffusion with a flux value of 11.73 μgcm^?2h^?1. Sustained drug concentration was obtained in NLCs carrying LMT after IN administration after 24 h. γ scintigraphy studies further proved high accumulation of drug in brain.

Conclusion: Hence we can conclude that IN administration of LMT NLCs in rats is able to maintain higher brain concentration of LMT compared to IN and oral drug solution.     

Preparation and characterization of a biodegradable drug targeting system for anticancer drug delivery: Microsphere-antibody conjugate

Targeted delivery of anticancer drugs is one of the most actively pursued goals in anticancer chemotherapy. A major disadvantage of anticancer drugs is their lack of selectivity for tumour tissue, which causes severe side effects and results in low cure rates. Any strategy by which a cytotoxic drug is targeted to the tumour, thus increasing the therapeutic index of the drug, is a way of improving cancer chemotherapy and minimizing systematic toxicity. This study covers the preparation of the gelatin microsphere (GM)-anti-bovine serum albumin (anti-BSA) conjugate for the development of a drug targeting approach for anticancer drug delivery. Microspheres of 5% (w/v) gelatin content were prepared by crosslinking with glutaraldehyde (GTA) at 0.05 and 0.50% (v/v) concentration. Microspheres were in the size range of 71–141 μm. The suitability of these microspheres as drug carriers for anticancer drug delivery was investigated in vitro by studying the release profiles of loaded methotrexate (MTX) and 5-fluorouracil (5-FU) and the cytotoxicities on cancer cell lines. The in vitro MTX release profiles (～22–46% released in 24 h depending on the amount of GTA used) were much slower compared to 5-FU (～42–91% released in 24 h). Both drugs demonstrated an initial fast release, which was followed by gradual, sustained drug release. The MTT cytotoxicity test results of GMs loaded with 5-FU and MTX showed ～54–70% and ～52–67% cytotoxicities in 4 days. In general, incorporation of MTX and 5-FU in microspheres enhanced the cytotoxic effect in a more prolonged manner compared to the free drugs. Gelatin micospheres were chemically conjugated to anti-BSA and the antigen–antibody activities were studied by immunofluorescence. Results indicated ～80% binding with conjugated anti-BSA and BSA-FITC. Based on their low cytotoxicity and the high antigen binding efficiencies, anti-BSA conjugated gelatin microspheres could be suitable targeted drug carrier systems for selective and long-term delivery of anticancer drugs to a specific body compartment (i.e. bladder cancer).     

Vincristine and temozolomide combined chemotherapy for the treatment of glioma: a comparison of solid lipid nanoparticles and nanostructured lipid carriers for dual drugs delivery

Context: Glioma is a common malignant brain tumor originating in the central nervous system. Efficient delivery of therapeutic agents to the cells and tissues is a difficult challenge. Co-delivery of anticancer drugs into the cancer cells or tissues by multifunctional nanocarriers may provide a new paradigm in cancer treatment.

Objective: In this study, solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were constructed for co-delivery of vincristine (VCR) and temozolomide (TMZ) to develop the synergetic therapeutic action of the two drugs. The antitumor effects of these two systems were compared to provide a better choice for gliomatosis cerebri treatment.

Methods: VCR- and TMZ-loaded SLNs (VT-SLNs) and NLCs (VT-NLCs) were formulated. Their particle size, zeta potential, drug encapsulation efficiency (EE) and drug loading capacity were evaluated. The single TMZ-loaded SLNs and NLCs were also prepared as contrast. Anti-tumor efficacies of the two kinds of carriers were evaluated on U87 malignant glioma cells and mice bearing malignant glioma model.

Results: Significantly better glioma inhibition was observed on NLCs formulations than SLNs, and dual drugs displayed the highest antitumor efficacy in vivo and in vitro than all the other formulations used.

Conclusion: VT-NLCs can deliver VCR and TMZ into U87MG cells more efficiently, and inhibition efficacy is higher than VT-SLNs. This dual drugs-loaded NLCs could be an outstanding drug delivery system to achieve excellent therapeutic efficiency for the treatment of malignant gliomatosis cerebri.     

Cisplatin and paclitaxel co-delivered by folate-decorated lipid carriers for the treatment of head and neck cancer

Context: For head and neck cancer therapy, co-delivery of two drugs, cisplatin (DDP) plus paclitaxel (PTX), are more effective than single drug therapy. Lipid carriers are promising drug carriers for anti-cancer delivery.

Objective: The aim of this study is to construct a folate (FA) decorated nanostructured lipid carriers (NLCs) as nanocarriers for DDP and PTX delivery.

Materials and methods: In this study, DDP and PTX were incorporated into NLCs. Folate-PEG-DSPE (FA-PEG-DSPE) was synthesized and decorated the drugs-loaded NLCs (FA-DDP/PTX NLCs). Their average size, zeta potential, drug encapsulation efficiency, drug loading capacity, and in vitro drug release were evaluated. Head and neck cancer cells (FaDu cells) were used for the testing of in vitro cytotoxicity, and in vivo transfection efficiency of NLC was evaluated on mice bearing FaDu cells model.

Results: The size of FA-DDP/PTX NLCs was around 127?nm, with a positive zeta potential of 26.7?mV. FA-DDP/PTX NLCs showed the highest cytotoxicity and synergistic effect of two drugs in head and neck cancer cells (FaDu cells) in vitro. The in vivo study revealed the greatest anti-tumor activity than all the other formulations in murine-bearing head and neck cancer model.

Discussion and conclusion: FA-DDP/PTX NLCs effectively improves anticancer efficiency for head and neck cancer in vitro and in vivo. The constructed NLCs could be used as a novel carrier to co-delivery DDP and PTX for head and neck cancer therapy.     

Nanostructured Lipid Carriers for Oral Bioavailability Enhancement of Exemestane: Formulation Design,In Vitro,Ex Vivo,and In Vivo Studies

Exemestane (EXE) is a novel oral steroidal aromatase inhibitor approved for the treatment of breast cancer. However, its oral clinical application is limited because of low aqueous solubility and low oral bioavailability. Here, we aim to design and fabricate nanostructured lipid carriers (NLCs) using Precirol^® ATO 5 and flaxseed oil as the solid lipid and liquid lipid, respectively. EXE-loaded NLCs were spherical in shape and with a hydrodynamic diameter of 131.3 ± 2.43 nm, polydispersity index 0.205 ± 0.06, and percentage entrapment efficiency 85.6 ± 1.20%. In vitro release study demonstrated a sustained release pattern for 24 h, with relative burst release at the initial time point. Differential scanning calorimetry and powder X-ray diffraction studies showed reduced crystallinity and complete encapsulation of drug within the lipid matrix. Ex vivo gut permeation study and confocal laser scanning microscopy revealed that NLCs comprising a lipid blend and surfactant enhanced intestinal permeability of EXE. Moreover, in vivo pharmacokinetic study on female Wistar rats found to augment 3.9-fold in oral bioavailability of EXE through NLCs compared with EXE suspension. Herein, we depict that loading of EXE into NLCs hold promising approach for the oral delivery of EXE in cancer therapy.     

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 IC₅₀ 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 IC₅₀ of 1.28 µM and non-targeted nanoparticles gave IC₅₀ of 3.56 µM. 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.     

Local anesthetic lidocaine delivery system: chitosan and hyaluronic acid-modified layer-by-layer lipid nanoparticles

Context: Transdermal local anesthesia is one of the most applied strategies to avoid systemic adverse effects; there is an appealing need for a prolonged local anesthetic that would provide better bioavailability and longer pain relief with a single administration.

Objective: Layer-by-layer (LBL) technique was used in this study to explore a nanosized drug delivery system for local anesthetic therapy.

Materials and methods: LBL-coated lidocaine-loaded nanostructured lipid nanoparticles (LBL-LA/NLCs) were prepared and characterized in terms of particle size (PS), zeta potential, drug encapsulation efficiency (EE), in vitro skin permeation and in vivo local anesthetic studies.

Results: Evaluation of the in vitro skin permeation and in vivo anesthesia effect illustrated that LBL-LA/NLCs can enhance and prolong the anesthetic effect of LA.

Discussion and conclusion: LBL-LA/NLCs could function as a promising drug delivery strategy for overcoming the barrier function of the skin and could deliver anesthetic through the skin with sustained release behavior for local anesthetic therapy.     

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.     

Nanostructured lipid carriers of pioglitazone for transdermal application: from experimental design to bioactivity detail

Abstract

Pioglitazone (PZ) an anti-hyperglycemic agent is used in the treatment of type 2 diabetes. The aim of this study was to design PZ-loaded nanostructured lipid carriers (NLC) to investigate the bioavailability improvement by transdermal delivery. PZ NLCs were prepared using high-pressure homogenization followed by ultrasonication. The NLCs were evaluated for particle size analysis, drug loading, ex vivo skin transport studies and in vivo bioactivity study. The prepared NLCs had a mean size of 166.05?nm and drug loading of 10.41% with flux value of 47.36?µg/cm²/h. The entrapment of PZ is >70% in the NLCs with enhancement ratio of 3.2 times. The in vivo pharmacokinetic study showed 2.17 times enhancement in bioavailability study and pharmacodynamics study showed that PZ NLC-based transdermal therapeutic system (PNLG-TTS) lowers blood sugar level in a sustained pattern for a prolonged period of time as compared to Piosys tablet (marketed). The shelf life of the optimized formulation was found to be 1.83?years. These results clearly provide a lead that above NLCs-based TTS is potential controlled release formulation for PZ and could be a promising drug delivery system for the treatment of diabetes.     

Thermosensitive hydrogel containing sertaconazole loaded nanostructured lipid carriers for potential treatment of fungal keratitis

This study was conducted to develop an in situ thermosensitive gel containing sertaconazole-loaded nanostructured lipid carriers (NLCs) for prolonged ocular drug delivery. To this end, sertaconazole-loaded NLCs (sertaconazole-NLCs) were prepared by emulsification solvent-diffusion method and the effects of different formulation variables were assessed using the fractional factorial design. Then, optimized sertaconazole-NLCs were incorporated into the pluronic F127 (PF127)/hydroxy propylmethylcellulose (HPMC) K4M hydrogel. The formulations were examined for pH, gelation temperature, rheological properties, in vitro permeation studies, and anti-fungal activity. The optimized sertaconazole-NLCs showed a mean particle size of 272.40?nm, encapsulation efficiency of 89.97%, zeta potential of 12.9?mV, and polydispersity index of 0.31. All the in situ formulations had acceptable pH, ranging from 5.89 to 6.28. The gelation temperature of the optimized formulation was 35.1?°C after dilution with simulated tear fluid (STF). Sertaconazole-NLCs showed a higher antifungal activity and permeation through the bovine cornea compared to the free drug and the in situ gel formulation. The cornea penetration of sertaconazole for the in situ gel of NLCs was also comparable to that for free drug. The obtained results indicated that the prepared nanocomposite system may have potential for treatment of fungal keratitis.     

Microemulsions mediated effective delivery of methotrexate hydrogel: more than a tour de force in psoriasis therapeutics

Methotrexate (MTX), a well known drug for the treatment of cancer and rheumatoid arthritis, has gained prominence in the treatment of psoriasis over the period of years. However, the present mode of systemic administration through oral or parenteral route has always proposition, full of compromises. The toxicity of drug to the vital organs and physiological environment is the major concern. Also, its poor skin penetration is one major problem. Hence novel system based on lipid carriers has been considered here to overcome the barriers. Microemulsions (MEs) were prepared using pseudo-ternary phase diagram (PTPD) and they were characterized for various parameters such as size, shape (cryo-SEM), PDI, zeta potential, etc. The chosen MEs system (optimized) was then incorporated into secondary vehicles and characterized for rheological behavior, texture profile analysis, in vitro release, ex vivo permeation and drug distribution into different layers of skin. The developed formulations were further evaluated in ex vivo and in vivo such as cell line study, imiquimod-induced psoriatic model, allergic contact dermatitis, rat tail model (% orthokeratosis) and safety test (Draize test). The MEs based MTX gel has shown its potential in locating the drug at the desired domain of stratum corneum, epidermal and dermal layers of skin and reducing systemic absorption. Our results are suggestive of MEs potential as a novel carrier for topical delivery of MTX in topical therapeutic and safety approaches. In conclusion, developed MEs-based hydrogel has shown promising results in achieving effective delivery of MTX.     

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.     

High payload nanostructured lipid carriers fabricated with alendronate/polyethyleneimine ion complexes

Oral bioavailability of the anti-osteoporotic drug alendronate (AL) is limited to ≤ 1% due to unfavorable physicochemical properties. To augment absorption across the gastrointestinal mucosa, an ion pair complex between AL and polyethyleneimine (PEI) was formed and incorporated into nanostructured lipid carriers (NLCs) using a modified solvent injection method. When compared to free AL, ion pairing with PEI increased drug encapsulation efficiency in NLCs from 10% to 87%. Drug release from NLCs measured in vitro using fasted state simulated intestinal fluid, pH 6.5 (FaSSIF-V2) was significantly delayed after PEI complexation. Stability of AL/PEI was pH-dependent resulting in 10-fold faster dissociation of AL in FaSSIF-V2 than measured at pH 7.4. Intestinal permeation properties estimated in vitro across Caco-2 cell monolayers revealed a 3-fold greater flux of AL encapsulated as hydrophobic ion complex in NLCs when compared to AL solution (P_app?=?8.43?±?0.14?×?10^?6 cm/s and vs. 2.76?±?0.42?×?10^?6 cm/s). Cellular safety of AL/PEI-containing NLCs was demonstrated up to an equivalent AL concentration of 2.5 mM. These results suggest that encapsulation of AL/PEI in NLCs appears a viable drug delivery strategy for augmenting oral bioavailability of this clinically relevant bisphosphonate drug and, simultaneously, increase gastrointestinal safety.     

Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology

Purpose

To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles.

Methods

NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references.

Results

NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C _max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation.

Conclusion

Controlled release of integral NLCs is achieved by the osmotic pump strategy.

     

Honokiol-loaded polymeric nanoparticles: an active targeting drug delivery system for the treatment of nasopharyngeal carcinoma

The purpose of this study was to develop a novel drug delivery system for a sustained and targeted delivery of honokiol (HK) to the nasopharyngeal carcinoma (NPC) HNE-1 cell lines, since the folate receptor (FR) is over-expressed on their surface. Emulsion solvent evaporation was used to develop the active targeting nanoparticles-loaded HK (ATNH) using copolymerpoly (?-caprolactone)-poly (ethyleneglycol)-poly (?-caprolactone) (PCEC), which was modified with folate (FA) by introducing Polythylenimine (PEI). ATNH characterization, including particle size distribution, morphology, drug loading, encapsulation efficiency and drug release, was performed. Transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FTIR) were employed to evaluate the shape and construction, respectively. MTT assay, cell uptake study and apoptosis test were assayed to detect the antitumor properties and targeting uptake by HNE-1 cells in vitro. Cell-cycle redistribution, ^18?F-FDG PET/CT and immunohistochemistry were performed in vivo. The ATNH we developed were successfully synthesized and showed a suitable size distribution, high encapsulation efficiency, gradual release, and targeting uptake by the cells in vitro. Moreover, ATNH significantly inhibited tumor growth, metabolism, proliferation, micro-vessel generation, and caused cell-cycle arrest at G₁ phase. Thus, these nanoparticles we developed might represent a novel formulation for HK delivery and a promising potential therapy in the treatment of cancer.