Developing combination of artesunate with paclitaxel loaded into poly-d,l-lactic-co-glycolic acid nanoparticle for systemic delivery to exhibit synergic chemotherapeutic response

Objectives: Paclitaxel (PTX) has been indicated for the treatment of a variety of solid tumors, whereas artesunate (ART) has been reported to have the potential for use in combination chemotherapy. In this study, the combination of ART and PTX was prepared in nanoparticle to induce the synergic effect and improve therapeutic efficiency in treatment of breast cancer.

Methods: Dual anticancer agents (PTX and ART) were loaded into Poly-D,L-lactic-co-glycolic acid (PLGA) nanoparticle (NP) by solvent evaporation technique from oil-in-water emulsion, stabilized with Tween 80. Physicochemical properties of obtained nanoparticles (PTX-ART-NPs) were characterized including particle size (Z), polydispersity index (PDI), zeta potentials (ZP), encapsulation efficiency (EE), and in-vitro drug release. Combination index (CI) was calculated to determine the synergic effect of the combination and select the best ratio of ART and PTX. The final NPs analyzed intracellular uptake, cytotoxicity assay, and apoptosis study.

Results: The final NP had a small size (around 120?nm) with a narrow size distribution (PDI <0.3). EE values for each drug were 87.8?±?1.1% and 99.5?±?0.1% for ART and PTX, respectively, and drugs were released from NPs in a controlled release pattern. All combinations of PTX and ART had CI values under 1, which confirmed the synergic effects. Meanwhile, NP preparation increased cytotoxicity on three breast cancer cell-lines comparable to free drugs.

Conclusions: Combination of ART- and PTX-loaded PLGA NP showed promising results for anticancer therapy, especially for breast cancer treatment.     

Mannosylated solid lipid nanoparticles for lung-targeted delivery of Paclitaxel

Objective: The present study discusses paclitaxel (PTX)-loaded mannosylated-DSPE (Distearoyl-phosphatidyl-ethanolamine) solid lipid nanoparticles (M-SLNs) using mannose as a lectin receptor ligand conjugate for lung cancer targeting and to increase the anticancer activity of PTX against A549 lung’s epithelial cancer cells.

Materials and methods: The PTX-SLNs were prepared by solvent injection method and mannose was conjugated to the free amine group of stearylamine. The M-SLNs obtained were characterized for their particle size, polydispersity index, zeta potential and morphology by transmission electron microscope.

Results: The M-SLNs were spherical in shape with 254?±?2.3?nm average size, positive zeta potential (3.27?mV), 79.4?±?1.6 drug entrapment efficiency and showed the lower extent of drug release 40% over 48?h in vitro. Cytotoxicity study on A549 cell lines and biodistrubtion study of drug revealed that M-SLNs deliver a higher concentration of PTX as compared to PTX-SLNs in an alveolar cell site.

Discussion and conclusion: These results suggested that mannosylated M-SLNs are safe and potential vector for lung cancer targeting.     

Development and characterization of folate anchored Saquinavir entrapped PLGA nanoparticles for anti-tumor activity

Objective: Saquinavir (SQV) is a US-FDA approved HIV protease inhibitor (HPI) for HIV cure. The purpose of the present investigation was to develop and characterize the anticancer potential of the SQV-loaded folic acid (FA) conjugated PEGylated and non-PEGylated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) (SQV–Fol–PEG–PLGA and SQV–Fol–PLGA) employing PC-3 (human prostate) and MCF-7 (human breast) cancer cell lines.

Materials and methods: Developed NPs were characterized by IR, NMR, DSC, XRD, size, charge and further tested for drug loading and cellular uptake properties.

Result: The entrapment efficiency was found to be 56?±?0.60 and 58?±?0.80 w/v for SQV–Fol–PEG–PLGA and SQV–PLGA NPs, respectively. The obtained results of SQV–Fol–PEG–PLGA showed enhanced cytotoxicity and cellular uptake and were most preferentially taken up by the cancerous cells via folate receptor-mediated endocytosis (RME) mechanism. At 260?µM concentration, SQV–PLGA NPs and SQV–Fol–PEG–PLGA NPs showed 20%, 20% and 23% cell growth inhibition in PC-3 cells, respectively whereas in MCF-7 cells it was 12%, 15% and 14% cell growth inhibition, respectively.

Conclusions: Developed targeted SQV–Fol–PEG–PLGA NPs were superior anticancer potential as compared to non-targeted SQV–PLGA NPs. Thus, these targeted NPs provide another option for anticancer drug delivery scientists.     

Formulation and corneal permeation of ketorolac tromethamine-loaded chitosan nanoparticles

Abstract

The aim of this work was to formulate chitosan (CS)-based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimized in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterization studies using Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0?±?2.4?nm to 257.2?±?18.6?nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10?mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (p?<?0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT-loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS-based NPs for the ocular delivery of KT.     

Phospholipid–polymer hybrid nanoparticle-mediated transfollicular delivery of quercetin: prospective implement for the treatment of androgenic alopecia

Abstract

Objectives: The aim of the study was to deliver effective doses of quercetin (Que) to the lower region of hair follicles (HFs) using the transfollicular route through dipalmotylphosphatidylcholine (DPPC)-reinforced poly lactide-co- glycolide nanoparticles (DPPC-PLGA hybrid NPs) for the treatment of alopecia.

Method: PLGA and DPPC-PLGA hybrid NPs were prepared by double-emulsification solvent evaporation method. NPs were characterized for size, shape, zeta potential entrapment and drug release. Drug-polymer interactions were determined by infrared spectroscopy (Fourier transform infrared spectroscopy, FTIR) and differential scanning calorimetry (DSC). Follicular uptake of fluorescent marker tagged NPs was assessed on isolated rat skin by fluorescent microscopy. Potential of hybrid NPs to induce hair regrowth was tested on testosterone-induced alopecia in rat models by visual inspection, hair follicular density measurement (no./mm), and histological skin tissue section studies.

Key findings: Hybrid NPs had mean vesicles size 339?±?1.6, zeta potential –32.6?±?0.51, and entrapment efficiency 78?±?5.5. Cumulative drug release after 12?h was found to be 47.27?±?0.79%. FTIR and DSC confirmed that drug was independently dispersed in the amorphous form in the polymer. Data from fluorescence microscopy suggested that NPs were actively taken up by HFs. In-vivo studies on alopecia-induced rat models showed that hybrid NPs improved hair regrowth potential of Que and accumulation of NPs at HFs end region inhibit HFs cells apoptosis.

Conclusion: This study concludes that phospholipid–polymer hybrid NPs could be the promising transfollicular delivery system for Que in the treatment of androgenic alopecia management.     

PAMAM-modified citric acid-coated magnetic nanoparticles as pH sensitive biocompatible carrier against human breast cancer cells

Denderimer-modified magnetic nanoparticles are a promising drug delivery nanosystem which can improve the therapeutic efficacy of chemotherapy drugs and can also be beneficial as magnetic resonance (MR) images contrast agent. The present study introduces the preparation and characterization of the potential therapeutic efficiency of curcumin (CUR)-loaded denderimer-modified citric acid coated Fe₃O₄ NPs. Polyamidoamine (PAMAM, generation G₅) was used to encapsulate citric acid coated Fe₃O₄ nanoparticles. The successful preparation of CUR-loaded nanocarriers were confirmed by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometer (VSM), and transmission electron microscopy (TEM) techniques. The loading capacity and encapsulation efficiency of CUR molecules were 12?±?0.03% and 45.58?±?0.41%, respectively. The anticancer effect of void CUR and CUR-loaded nanocarriers were compared to each other by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on treated MCF-7 cell line. It can be concluded that application of nanoparticles can be more effective strategy for controlled and slow release of CUR in human breast cancer treatment.     

PEGylated nanostructured lipid carriers (PEG–NLC) as a novel drug delivery system for biochanin A

With the aim to develop a lipid nanoparticle for biochanin A (BCA) by emulsion-evaporation and low temperature-solidification technique. The results revealed that BCA–PEG–NLC not only have small mean particle (148.5?±?2.88?nm) with narrow polydispersity index (PI) (0.153?±?0.01), encapsulation capacity (99.62?±?0.06%), payload (9.06?±?0.01%), zeta potential (?19.83?±?1.19?mV), but also slower release rate compared with BCA suspension over 48?h by the dialysis method (n=3). The crystallinity of lipid matrix within BCA–PEG–NLC was evaluated by differential scanning calorimetry (DSC) which verified the BCA successfully into the nanoparticles. Particularly, in pharmacokinetic, the BCA–PEG–NLC of C_max values and AUC (area under curve) was higher than BCA suspension (approximately 15.8 and 2.9 times, respectively), meanwhile, the mean residence time (MRT) was significantly longer. Furthermore, in vitro cytotoxicity BCA–PEG–NLC showed higher cytotoxicity against MCF-7 cell line compared with BCA suspension. This study suggested that PEG–NLC is a novel anti-cancer nanoparticle, which could provide attractive treatment for a wide variety of tumors and improved the oral bioavailability of poorly water-soluble drug.     

Chitosan based mucoadhesive nanoparticles of ketoconazole for bioavailability enhancement: formulation,optimization, in vitro and ex vivo evaluation

Purpose: The conventional dosage form of Ketoconazole (KZ) shows poor absorption due to rapid gastric emptying. Chitosan based mucoadhesive nanoparticles (NPs) of KZ were developed to efficiently release drug at its absorption window i.e. stomach and the site of action i.e. esophagus.

Method: The NPs were prepared by ionic gelation method. Concentration of polymer, cross-linking agent and ratio of drug/polymer as well as polymer/cross linking agent were optimized.

Results: NPs had 69.16?±?5.91% mucin binding efficiency, particle size of 382.6?±?2.384?nm, ζ potential of +48.1?mv and entrapment efficiency of 59.84 ± 1.088%. DSC thermogram indicated absence of any drug polymer interaction. The drug release was by controlled, non-fickian diffusion mechanism. Ex vivo diffusion studies were performed by emptying the stomach contents after 2?h to simulate in vivo gastric emptying. The results showed that drug diffusion from the solution across stomach mucosa stopped after emptying whereas that from the NPs continued upto 5?h. Hence we could conclude that the NPs must have adhered to the stomach mucosa and thereby would have been retained at this absorption site even after gastric emptying.

Conclusion: The orally delivered KZ loaded mucoadhesive NPs can be used as an efficient carrier for delivering drug at its absorption window i.e. the stomach and the site of action i.e. esophagus even after gastric emptying.     

Comparison of antibacterial activity of Ag nanoparticles synthesized from leaf extract of Parthenium hystrophorus L in aqueous media and Gentamicin sulphate: in-vitro

Monodisperse silver (Ag) nanoparticles were synthesized by using Parthenium hystrophorus L leaf extract in aqueous media. The synthesized nanoparticles were characterized by using UV-vis spectrophotometer, X-ray diffracto-meter (XRD), transmission electron microscope (TEM), and dynamics light scattering (DLS). Size-dependent antibacterial activities of Ag nanoparticles were tested against Gram negative Pseudomonas aeruginosa and Gram positive Staphylococcus aureus. Ag nanoparticles having 20?±?2?nm size in diameter show maximum zone of inhibition (23?±?2.2?mm) in comparison to 40?nm and 70?nm diameter nanoparticles for Pseudomonas aeruginosa. The zone of inhibition against Staphylococcus aureus were 19?±?1.8?mm, 15?±?1.5?mm and 11?±?1?mm for 20?nm, 40?nm, and 70?nm, respectively. In addition, affect of concentration of 20?nm size Ag nanoparticles on Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus species were also reported and results were compared with 10?µg/ml dose of Gentamicin sulphate. The Parthenium hystrophorus L leaf extract capped 20?±?2?nm Ag nanoparticles (7.5?µg/ml) shows statistically significant antibacterial activity than Gentamicin sulphate (10?µg/ml) against Staphylococcus aureus.     

A reconstituted thermosensitive hydrogel system based on paclitaxel-loaded amphiphilic copolymer nanoparticles and antitumor efficacy

Combination delivery systems composed of injectable hydrogels and drug-incorporated nanoparticles are urgently in regional cancer chemotherapy to facilitate efficient delivery of chemotherapeutic agents, enhance antitumor efficiency, and decrease side effects. Here, we developed a novel thermosensitive amphiphilic triblock copolymer consisting of methoxy poly(ethylene glycol), poly(octadecanedioic anhydride), and d,l-lactic acid oligomer (PEOALA), built a combination system of thermosensitive injectable hydrogel PTX/PEOALA^Gel based on paclitaxel (PTX)-loaded PEOALA nanoparticles (NPs). PTX/PEOALA^Gel could be stored as freeze-dried powders of paclitaxel-loaded PEOALA NPs, which could be easily redispersed into the water at ambient temperature, and form a hydrogel at the injected site in vivo. The in vitro cytotoxicity of PTX/PEOALA^Gel showed no obvious cytotoxicity in comparison with Taxol® against MCF-7 and HeLa cells. However, the in vivo antitumor activity showed that a single intratumoral injection of the PTX/PEOALA^Gel formulation was more effective than four intravenous (i.v.) injections of Taxol^® at a total dosage of 20?mg/kg in inhibiting the growth of MCF-7 tumor-bearing Balb/c mice, and the inhibition could be sustained for more than 17 d. The pharmacokinetic study demonstrated that the intratumoral injection of PTX/PEOALA^Gel could greatly decrease the systemic exposure of PTX, as confirmed by the rather low plasma concentration, and prolonged circulation time and enhanced tumor PTX accumulation, implying fewer off-target side effects. In summary, the PTX/PEOALA^Gel combination local delivery system could enhance tumor inhibition effect and tumor accumulation of PTX, and lower the systemic exposure. So, the reconstituted PTX/PEOALA^Gel system could potentially be a useful vehicle for regional cancer chemotherapy.     

Preparation and optimization of doxorubicin-loaded albumin nanoparticles using response surface methodology

Background: The objective of this work was to optimize the preparation of doxorubicin-loaded albumin nanoparticles (Dox-A-Nps) through desolvation procedures using response surface methodology (RSM). A central composite design (CCD) for four factors at five levels was used in this study.

Method: Albumin nanoparticles were prepared through a desolvation method and were optimized in the aid of CCD. Albumin concentration, amount of doxorubicin, pH values, and percentage of glutaraldehyde were selected as independent variables, particle size, zeta potential, drug loading, encapsulation efficiency, and nanoparticles yield were chosen as response variables. RSM and multiple response optimizations utilizing a quadratic polynomial equation were used to obtain an optimal formulation.

Results: The optimal formulation for Dox-A-Nps was composed of albumin concentration of 17?mg/ml, amount of doxorubicin of 2?mg/ml, pH value is 9 and percentage of glutaraldehyde of 125% of the theoretic amount, under which the optimized conditions gave rise to the actual average value of mean particle size (151?±?0.43?nm), zeta potential (?18.8?±?0.21 mV), drug loading efficiency (21.4?±?0.70%), drug entrapment efficiency (76.9?±?0.21%) and nanoparticles yield (82.0?±?0.34%). The storage stability experiments proved that Dox-A-Nps stable in 4°C over the period of 4 months. The in vitro experiments showed a burst release at the initial stage and followed by a prolonged release of Dox from albumin nanoparticles up to 60?h.

Conclusions: This study showed that the RSM-CCD method could efficiently be applied for the modeling of nanoparticles, which laid the foundation of the further research of immuno nanoparticles.     

Brain pharmacokinetics of neurotoxin-loaded PLA nanoparticles modified with chitosan after intranasal administration in awake rats

Context: Neurotoxin (NT), an analgesic peptide which was separated from the venom of Naja naja atra, is endowed an exceptional specificity of action that blocks transmission of the nerve impulse by binding to the acetylcholine receptor in the membrane. However, it has limited permeability across the blood-brain barrier (BBB).

Objective: The purpose of this study was to encapsulate NT within polylactic acid (PLA) nanoparticles (NPs) modified with chitosan (NT-PLA-cNPs) and to evaluate their brain pharmacokinetic behaviors after intranasal (i.n.) administration using a microdialysis technique in free-moving rats.

Methods: NT-PLA-cNPs (NT labeled with fluorescein isothiocyanate) were prepared and characterized. Then, NT-PLA-cNPs were i.n. administered to rats and the fluorescence intensity in the periaqueductal gray (PAG) was monitored for up to 480?min, with NT-PLA-NPs and NT solution as control groups.

Results: The NPs prepared were spherical with a homogenous size distribution. The mean particle size, zeta potential, and entrapment efficiency were 140.5?±?5.4?nm, +33.71?±?3.24 mV, and 83.51?±?2.65%, respectively. The brain transport results showed that T_max of NT-PLA-cNPs was equal with that of NT-PLA-NPs after i.n. administration (150?min). The C_max and AUC_{0–8 h} of each group followed the following order: NT-PLA-cNPs > NT-PLA-NPs. The corresponding absolute bioavailability (F_abs) of NT-PLA-cNPs was about 151% with NT-PLA-NPs as reference preparations.

Conclusion: These results suggest that NPs modified with chitosan have better brain targeting efficiency and are a promising approach for i.n. delivery of large hydrophilic peptides and proteins in improving the treatment of central nervous system (CNS) disorders.     

Methotrexate-conjugated L-lysine coated iron oxide magnetic nanoparticles for inhibition of MCF-7 breast cancer cells

Methotrexate (MTX), a stoichiometric inhibitor of dihydrofolate reductase enzyme, is a chemotherapeutic agent for treating a diversity of neoplasms. In this study, we design and developed a new formulation of MTX that serves as drug carrier and examined its cytotoxic effect in vitro. This target drug delivery system is dependent on the release of the MTX within the lysosomal compartment. The iron oxide magnetic nanoparticles (IONPs) were first surface-coated with L-lysine and subsequently conjugated with MTX through amidation between the carboxylic acid end groups on MTX and the amine groups on the IONPs surface. MTX-conjugated L-lysine coated IONPs (F-Lys-MTX NPs) was characterized by X-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, vibrating sample magnetometer, and transmission electron microscopy techniques. The cytotoxicity of the void of MTX and F-Lys-MTX NPs were compared to each other by MTT assay of the treated MCF-7 cell lines. The results showed that the ζ-potential of F-Lys-MTX NPs was about ?5.49?mV and the average size was 43.72?±?4.73?nm. Model studies exhibited the release of MTX via peptide bond cleavage in the presence of proteinase K and at low pH. These studies specify that F-Lys-MTX NPs have a very remarkable anticancer effect, for breast cancer cell lines.     

Physicochemical stability,pharmacokinetic, and biodistribution evaluation of paclitaxel solid dispersion prepared using supercritical antisolvent process

Aim: To investigate the physicochemical stability, pharmacokinetics (PK), and biodistribution of paclitaxel (PTX) from paclitaxel solid dispersion (PSD) prepared by supercritical antisolvent (SAS) process.

Methods: Physicochemical stability was performed in accelerated (40°C 70?±?5% RH) and stress (60°C) storage conditions for a period of 6 months and 4 weeks, respectively. PK and biodistribution studies were performed in rats following i.v. administration of PTX equivalent to 6 and 12?mg/kg formulations.

Results: Physical stability of PSD showed excellent stability with no recrystallization of the amorphous form. Chemical stability of PSD in terms of % PTX remaining was 98.2?±?0.6% at 6 months and 97.9?±?0.3% at 4 weeks of accelerated and stress conditions, respectively. The PK study showed a nonlinear increase in AUC with increasing dose, that is, 100% increase in dose (from 6 to 12?mg/kg) resulted in 405.90% increase in AUC. Unlike PK study, the organ distribution study of PTX from PSD showed linear relationship with dose escalation. The order of organ distribution of PTX from highest to lowest for both PSD and Taxol^® was liver>kidney>lung>brain.

Conclusions: This study demonstrated excellent physicochemical stability with insight information on the PK and biodistribution of PTX from PSD prepared by SAS process.     

Influence of different sulfur sources on the phase formation of Cu<Subscript>2</Subscript>ZnSnS<Subscript>4</Subscript> (CZTS) nanoparticles (NPs)

Wurtzite (Wz) and kesterite (Ks) phases of Cu₂ZnSnS₄ (CZTS) nanoparticles (NPs) have been selectively synthesized via hot injection method using 1-octadecene (1-ODE) as solvent. The solvents, 1-dodecanethiol (1-DDT) and tert-dodecanethiol (t-DDT) were utilized to control the reactivity of metal precursors and to tune the desirable crystallographic phases. The phase purity of the as synthesized CZTS NPs was confirmed using X-ray diffraction results. TEM images indicate that the developed nanoparticles consist of a mixture of triangular shaped (height 20?±?3 nm, width 17?±?2 nm) and sphere shaped NPs (13.4?±?0.4 nm). These nanoparticles were formed due to the influence of thiols without any additional capping ligands. The band gap of as-synthesized CZTS NPs were calculated as 1.41 eV for wurtzite phase (Wz—1-DDT) and 1.47 eV for kesterite phase (Ks—t-DDT) from UV–Visible absorption results. CZTS thin films were prepared via spin coating and the electrical properties were analysed using Hall Effect measurements. Both the phases of CZTS films exhibit p-type conductivity. Wurtzite phase of CZTS has higher mobility (23.6 cm^?3) and carrier concentration (2.64?×?10¹⁷) compared to kesterite phase of CZTS films.     

Biodegradable nanoparticles for improved kidney bioavailability of rhein: preparation,characterization, plasma,and kidney pharmacokinetics

The aim of this work is to develop biodegradable nanoparticles for improved kidney bioavailability of rhein (RH). RH-loaded nanoparticles were prepared using an emulsification solvent evaporation method and fully characterized by several techniques. Kidney pharmacokinetics was assessed by implanting a microdialysis probe in rat's kidney cortex. Blood samples were simultaneously collected (via femoral artery) for assessing plasma pharmacokinetics. Optimized nanoparticles were small, with a mean particle size of 132.6?±?5.95?nm, and homogeneously dispersed. The charge on the particles was nearly zero, the encapsulation efficiency was 62.71?±?3.02%, and the drug loading was 1.56?±?0.15%. In vitro release of RH from the nanoparticles showed an initial burst release followed by a sustained release. Plasma and kidney pharmacokinetics showed that encapsulation of RH into nanoparticles significantly increased its kidney bioavailability (AUC_kidney/AUC_plasma?=?0.586?±?0.072), clearly indicating that nanoparticles are a promising strategy for kidney drug delivery.     

Bortezomib-loaded solid lipid nanoparticles: preparation,characterization, and intestinal permeability investigation

Bortezomib (BTZ), a proteasome inhibitor, is clinically used for the treatment of multiple myeloma and mantle cell lymphoma via intravenous or subcutaneous administration. Since BTZ has limited intestinal permeability, in this study, solid lipid nanoparticles (SLNs) were selected as lipid carrier to improve the intestinal permeability of BTZ. The nanoparticles were prepared by hot oil-in-water emulsification method and characterized for physicochemical properties. Moreover, in situ single-pass intestinal perfusion technique was used for intestinal permeability studies. Mean particle size of the BTZ-loaded solid lipid nanoparticles (BTZ-SLNs) was 94.6?±?0.66?nm with a negative surface charge of –18?±?11?mV. The entrapment efficiency of the BTZ-SLNs was 68.3?±?3.7% with a drug loading value of 0.8?±?0.05%. Cumulative drug release (%) over 48?h, indicated a slow release pattern for nanoparticles. Moreover, the SEM image showed a spherical shape and uniform size distribution for nanoparticles. Also, FTIR analysis indicated that BTZ was successfully loaded in the SLNs. The results of the intestinal perfusion studies revealed an improved effective permeability for BTZ-SLNs with a P_eff value of about threefold higher than plain BTZ solution.     

Fabrication of solid lipid nanoparticles of lurasidone HCl for oral delivery: optimization,in vitro characterization,cell line studies and in vivo efficacy in schizophrenia

Objective: The aim of the present investigation was to investigate the efficacy of solid lipid nanoparticles (SLNs) to enhance the absorption and bioavailability of lurasidone hydrochloride (LH) following oral administration.

Methods: The LH loaded SLNs (LH-SLNs) were prepared by high pressure homogenization (HPH) method, optimized using box Behnken design and evaluated for particle size (PS), entrapment efficiency (EE), morphology, FTIR, DSC, XRD, in vitro release, ex vivo permeation, transport studies across Caco-2 cell line and in vivo pharmacokinetic and pharmacodynamic studies.

Results: The LH-SLNs had PS of 139.8?±?5.5?nm, EE of 79.10?±?2.50% and zeta potential of ?30.8?±?3.5?mV. TEM images showed that LH-SLNs had a uniform size distribution and spherical shape. The in vitro release from LH-SLNs followed the Higuchi model. The ex vivo permeability study demonstrated enhanced drug permeation from LH-SLNs (>90%) through rat intestine as compared to LH-suspension. The SLNs were found to be taken up by energy dependent, endocytic mechanism which was mediated by clathrin/caveolae-mediated endocytosis across Caco-2 cell line. The pharmacokinetic results showed that oral bioavailability of LH was improved over 5.16-fold after incorporation into SLNs as compared to LH-suspension. The pharmacodynamic study proved the antipsychotic potential of LH-SLNs in the treatment of schizophrenia.

Conclusion: It was concluded that oral administration of LH-SLNs in rats improved the bioavailability of LH via lymphatic uptake along with improved therapeutic effect in MK-801 induced schizophrenia model in rats.     

Design,characterization, and evaluation of intranasal delivery of ropinirole-loaded mucoadhesive nanoparticles for brain targeting

Context: Parkinson disease (PD) is a common, progressive neurodegenerative disorder, characterized by marked depletion of striatal dopamine and degeneration of dopaminergic neurons in the substantia nigra.

Objective: The purpose of the present study was to investigate the possibility of targeting an anti-Parkinson’s drug ropinirole (RH) to the brain using polymeric nanoparticles.

Materials and methods: Ropinirole hydrochloride (RH)-loaded chitosan nanoparticles (CSNPs) were prepared by an ionic gelation method. The RH-CSNPs were characterized for particle size, polydispersity index (PDI), zeta potential, loading capacity, entrapment efficiency in vitro release study, and in vivo distribution after intranasal administration.

Results and discussion: The RH-CSNPs showed sustained release profiles for up to 18?h. The RH concentrations (% Radioactivity/g) in the brain following intranasal administration (i.n.) of RH-CSNPs were found to be significantly higher at all the time points compared with RH solution. The concentration of RH was highest in the liver (7.210?±?0.52), followed by kidneys (6.862?±?0.62), intestine (4.862?±?0.45), and lungs (4.640?±?0.92) in rats following i.n. administration of RH-CSNPs. Gamma scintigraphy imaging in rats was performed to ascertain the localization of drug in the brain following intranasal administration of formulations. The brain/blood ratios obtained (0.251?±?0.09 and 0.386?±?0.57 of RH (i.n.) and RH-CSNPs (i.n.), respectively) at 0.5?h are indicative of direct nose to brain transport, bypassing the blood–brain barrier (BBB).

Conclusion: The novel formulation showed the superiority of nose to brain delivery of RH using mucoadhesive nanoparticles compared with other delivery routes reported earlier.     

Preparation and evaluation of charged solid lipid nanoparticles of tetrandrine for ocular drug delivery system: pharmacokinetics,cytotoxicity and cellular uptake studies

In this study, tetrandrine-loaded cationic solid lipid nanoparticles (TET-CNP) and solid lipid nanoparticles (TET-NP) were prepared by the emulsion evaporation-solidification at low temperature method. The particle size, zeta potential, and entrapment efficiency of TET-CNP and TET-NP were characterized. The results showed that the TET-CNP and TET-NP had average diameters of (15.29?±?1.34) nm and (18.77?±?1.23) nm with zeta potentials of (5.11?±?1.03) mV and (?8.71?±??1.23) mV and entrapment efficiencies of (94.1?±?2.37)% and (95.6?±?2.43)%, respectively. In vitro release studies indicated that the TET-CNP and TET-NP retained the drug entity better than tetrandrine ophthalmic solutions (TET-SOL). In the pharmacokinetics studies, the AUC values of TET-CNP and TET-NP were 1.96-fold and 2.00-fold higher than that of TET-SOL (?p?C_max values of TET-CNP and TET-NP were 2.45-fold and 2.53-fold higher than that of the TET-SOL (p?相似文献