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Abstract The effect of chemotherapy for anti-glioblastoma is limited due to insufficient drug delivery across the blood–brain–barrier. Poloxamer 188-coated nanoparticles can enhance the delivery of nanoparticles across the blood–brain–barrier. This study presents the design, preparation, and evaluation of a combination of PLGA nanoparticles (PLGA NPs) loaded with methotrexate (P-MTX NPs) and PLGA nanoparticles loaded with paclitaxel (P-PTX NPs), both of which were surface-modified with poloxamer188. Cranial tumors were induced by implanting C6 cells in a rat model and MRI demonstrated that the tumors were indistinguishable in the two rats with P-MTX NPs + P-PTX NPs treated groups. Brain PET scans exhibited a decreased brain-to-background ratio which could be attributed to the diminished metabolic tumor volume. The expression of Ki-67 as a poor prognosis factor, was significantly lower in P-MTX NPs + P-PTX NPs compared to the control. Furthermore, the biodistribution of PLGA NPs was determined by carbon quantum dots loaded into PLGA NPs (P-CQD NPs), and quantitative analysis of ex-vivo imaging of the dissected organs demonstrated that 17.2 ± 0.6% of the NPs were concentrated in the brain after 48 h. The findings highlight the efficacy of combination nanochemotherapy in glioblastoma treatment, indicating the need for further preclinical studies.

Glioma is the most common primary cancer of central nervous system due to its rapid proliferation and high lethality. In this study, a novel poloxamer188‐based drug delivery system, poloxamer188‐poly(1,4,8‐trioxaspiro[4.6]undecan‐9‐one)‐poly(1,3‐dioxan‐2‐one) nanoparticles (P188TT NPs) were developed. The 1H NMR, Raman and FITC spectra demonstrated that P188TT copolymer was successfully synthesized. The critical micelle concentration (CMC) measurement showed that P188TT NPs had a low CMC. The characterization and bio‐safety assessment verified that P188TT NPs had the appropriate size, zeta potential, good stability, and ideal bio‐safety. In addition, the curcumin‐loaded P188TT NPs (Cur/P188TT NPs) were fabricated and then analyzed by differential scanning calorimeter (DSC) and thermalgravimetric analysis (TGA). The in vitro release study displayed that the release rate of Cur from Cur/P188TT NPs in pH 6.8 was appreciably faster than that in pH 7.4. The tissue distribution study showed that these NPs had good brain‐targeting efficiency. The cellular uptake assay suggested that P188TT NPs could promote the uptake of Cur in glioma cells. The MTT tests indicated that P188TT NPs could increase the anti‐tumor activity of encapsulated drugs. Therefore, P188TT NPs showed potential as a brain targeting nano‐carrier for glioma therapy, which required further validation in glioma models in vivo. [ABSTRACT FROM AUTHOR]

Atorvastatin is anti lipedimic drug. It belongs to class II under BCS and possess low oral bioavailability (< 26%) due to its poor aqueous solubility. purpose of study was to enhance aqueous solubility of Atorvastatin by three different approaches; solid dispersion, complexation and selfemulsification. solid dispersion was prepared by solvent evaporation method using poloxamer 188 as carrier. In complexation technique, inclusion complex of drug and β- cyclodextrin was formulated following solvent evaporation technique. In selfemulsification method soya bean oil, tween 80 and PEG 400 were used as oil, surfactants and co-surfactant respectively. prepared formulations were characterized for compatibility, solubility phase. In comparison to pure drug and physical mixtures of different carriers used, both drug solubility and its dissolution rate were significantly increased from different preparations. Among all methods solid dispersion (SD_ATN_3) containing drug: poloxamer188 in ratio of 1:4 showed rapid and higher drug release (88.36% within 45 min). in-vitro drug release data was fitted to various kinetic models and all formulations showed first order kinetics following super case II mechanism. increase in dissolution rate of Atorvastatin from solid dispersion of poloxamer 188 might be due to reduction of crystal size of drug, conversion of drug to amorphous or microcrystalline state and hence decreasing hydrophobicity of drug. increase in solubility of Atorvastatin was found in order; solid dispersion> complexation> selfemulsification > pure drug. [ABSTRACT FROM AUTHOR]

Cinnamon extract has received significant attention due to its significant antibacterial, antifungal, antioxidant, and even anti-cancer properties. The purpose of this study was to create cinnamon-extract-loaded PLGA nanoparticles and evaluate their physiochemical characteristics and cytotoxicity against the C6 cell line. Physiochemical characteristics, such as the mean diameter, zeta potential, and drug loading potential, were measured. The antioxidant activity and cytotoxicity of nanoparticles were investigated by DPPH and MTT studies, respectively. The mean diameter of nanoparticles was 120 ± 24 nm. The antioxidant activity of the cinnamon extract was mostly preserved in nanoparticles and the toxicity effect on cancer cells was investigated.

Poloxamer (PL)188 is a commonly used pharmaceutical excipient with unique physicochemical properties. In this study, an MSALL quantitative method for the determination of PL188 in rat plasma by UHPLC–Q‐TOF/MS was developed and validated. PL188 was analyzed on PLRP‐S reversed‐phase column (50 × 4.6 mm, 8 μm, 1,000 Å) with mobile phase 0.1% formic acid–water and 0.1% formic acid in acetonitrile–isopropanol (2:3, v/v). The liner range was 0.1–10.0 μg/ml. A pharmacokinetic study was performed on rats at a dose of 5 mg/kg by intravenous injection. The pharmacokinetic parameters of intravenous injection were as follows: half‐life was 2.0 ± 1.1 h, volume of distribution was 5.1 ± 3.2 L/kg, area under the concentration–time curve was 3.0 ± 0.6 μg/L h and clearance was 1.7 ± 0.3 L/h/kg. The results indicated that PL188 could be rapidly distributed to tissues with a high clearance rate. This study can provide a good reference for the further study of PL188. [ABSTRACT FROM AUTHOR]

Valsartan has shown to be effective against diabetic neuropathy. In this study we designed, developed and characterized valsartan loaded solid lipid nanoparticles to enhance the protection against diabetic neuropathy. Nerve function parameters and behavioural studies were performed in male mice. Valsartan-loaded solid lipid nanoparticles (VSLNs) were formulated using palmitic acid as lipid and poloxamer188 as surfactant by solvent diffusion method. VSLNs were characterized for particle size and zeta potential analysis, morphology, drug entrapment efficiency and drug loading. In vitro drug release studies were performed in phosphate buffer of pH 7.4 by using dialysis bag method. In vivo studies such as motor nerve conduction velocity, thermal nociception and mechanical nociception studies were performed with both VSLNs and pure drug. The optimized batch was the one with 1:2 ratio of drug and lipid, and 1% surfactant was found to have the particle size of 457 nm, zeta potential of –16 mV, entrapment efficiency of 78.9±0.05%, drug loading of 26.22±0.05% and in vitro drug release of 84.84±0.07% over a period of 24 h. Based on these results, we concluded that VSLNs showed better protection from diabetic neuropathy.

Objective(s): Nanoparticles offer an attractive platform for drug delivery through a wide variety of the body's physiological barriers. Furthermore, modification of nanoparticle surface with moeites such as Poloxamer188 can enhance their accumulation and localization at disease site. In this work, we investigated the physiochemical effect of a scavenger receptor (SR-BI) interacting moiety coated on the surface of methotrexate (MTX)-loaded PLGA nanoparticles. Methods: Methotrexate-loaded PLGA nanoparticles were prepared by a single step nanoprecipitation technique. The prepared nanoparticles were characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM) for their size and morphology respectively. In vitro drug encapsulation efficiency (EE) and relative drug loading (DL) of nanoparticles were examined by UV-Vis spectrophotometry. Results: The results showed that the mean diameter of nanoparticles and zeta potential increased when more poloxamer188 was added to preparation process.The DL and EE of MTX increased with increase in poloxamer188/PVA ratio. In vitro release of MTX from PLGA nanoparticle was extended by increasing poloxamer188 in preparation process. Conclusions: MTX loaded PLGA nanoparticle modified with PVA and poloxamer 188 with suitable sizes and physiochemical properties can potentially improve drug delivery.

Poloxamer188 (PL188), as one of the most commonly used pharmaceutical excipients, has unique physicochemical properties and good biocompatibility, and so is playing an increasingly extensive role in the field of medicine. Currently, there are few studies on the tissue distribution of PL188 in vivo. In this study, the LC-MS method based on MSALL technique of quadrupole time of flight mass spectrometry for absolute quantitative analysis of poloxamer 188 in biological substrates was established for the first time. The tissue distribution of poloxamer188 in SD rats were studied using the established quantitative analysis method. To explore the distribution of PL188 in organs and tissues, PL188 was administered via rat tail vein at a dose of 5 mg/kg. Eight kinds of tissues including heart, liver, spleen, lung, kidney, stomach, muscle and brain of rats were collected at 0.25 h, 1 h and 4 h after administration. Tissue distributions showed the highest level was observed in kidney, then in stomach, which indicated PL188 mainly bioaccumulated in the kidney. This study can provide references for the further study of PL188.

The objective of this study was to enhance dissolution and permeation of a low soluble, absorbable fexofenadine hydrochloride (FFH) by preparing solid dispersions using polyethylene glycol 20,000 (PEG 20,000) and poloxamer 188 as carriers. The phase solubility measurement for the supplied FFH revealed a linear increase in the solubility of fexofenadine with increasing carrier concentration in water (1.45 mg/mL to 11.78 mg/mL with 0% w/v to 30% w/v PEG 20,000; 1.45 mg/mL to 12.27 mg/mL with 0% w/v to 30% w/v poloxamer 188). To select the appropriate drug carrier concentration, a series of solid dispersions were prepared in the drug carrier weight ratios of 1:1, 1:2 and 1:4 by fusion method. The solid dispersions composed of drug carrier at 1:4 weight ratio showed highest dissolution with the time required for the release of 50% of the drug 120 min). The intestinal absorption study presented a significant improvement in the absorption of drug from the solid dispersions composed of poloxamer 188 than PEG 20,000. In summary, the solid dispersions of FFH prepared using PEG 20,000 and poloxamer 188 demonstrated improved dissolution and absorption than supplied FFH and could be used to improve the oral bioavailability of fexofenadine.

Xiaofeng Yang,1 Yingying Liu,1,2 Yanna Zhao,1 Meihua Han,1 Yifei Guo,1 Haixue Kuang,2 Xiangtao Wang1 1Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2School of Pharmacy, Heilongjiang University of Traditional Chinese Medicine, Harbin, People’s Republic of China Abstract: 10-Hydroxycamptothecin (10-HCPT) is a promising anticancer drug with a wide spectrum of antitumor activities. Due to its poor solubility, the carboxylate form that shows high water solubility but minimal anticancer activity and pharmacokinetic defects is used in the marketed 10-HCPT injections, resulting in its limited clinical application. To develop a simple, safe, and highly effective drug delivery system, a modified acid–base microprecipitation combined with a high-pressure homogenization technique was adopted to prepare 10-HCPT nanocrystals. Neither organic solvents nor stabilizers were employed throughout the preparation process. The in vitro and in vivo performances of the resulting10-HCPT nanocrystals were investigated systematically. The nanocrystals were spherical with a small size of ~130 nm, and the actual drug-loading content was as high as 75%. The nanocrystals displayed a sustained release pattern and were proven to have a higher cell uptake and antiproliferative activity than the 10-HCPT injections. The 10-HCPT nanocrystals also showed enhanced drug accumulation in tumors and better anticancer efficacy in 4T1-bearing mice. In summary, the 10-HCPT nanocrystals prepared in this study seem to be a promising delivery system for a new form of 10-HCPT dosages. Keywords: 10-hydroxycamptothecin, drug delivery, poloxamer 188, high drug payload, 4T1 cells

Objective: To prepare and utilize a novel Titanium surface affinity drug loaded nanoparticles to build a Titanium/ nanoparticle complex which could be used for drug delivery and release. Methods: (1) The synthesis and characterization of dopamine modified non-ionic surfactants, Dop-Poloxamer188. (2) Using Dop-Poloxamer188 as a surfactant, PLGA as oil phase matrix and model drugs, drug-loaded nanoparticles were prepared and characterized. (3) With pretreatment of the titanium plate, Dop-functionalized nanoparticles and titanium plate self-assembled into a Titanium/nanoparticles (Ti/NP). (4) The characterization of Ti/NP complex. Results: The new compound Dop - Poloxamer188 had an ultraviolet absorption peak at about 285 nm, indicating that the successful modification of dopamine to Poloxamer188; the Dop-Poloxamer188-PLGA nanoparticels had an average diameter of around 110 nm with polydispersity index (PDI) less than 0.1. Furthermore, Dopamine modified nanoparticles were immobilized on titanium surface through a simple dipping process. Water contact angle test, field-emission scanning electron microscope (Fe-SEM), fluorescence microscopic analysis and X-ray photoelectron spectroscopy (XPS) detection confirmed that dopamine modified nanoparticles were immobilized on titanium surface. Conclusions: This study successfully constructed a novel drug-loaded nanoparticles which could be immobilized on titanium surface. The novel drug loaded Ti/NP complex had the potential to be used for site specific drug delivery and controlled release in the broad area of Ti based biomaterials. [ABSTRACT FROM AUTHOR]

Poloxamer188 composite poly L-lactic acid (PLLA) electrospun fibrous nonwovens (EFNW) were prepared by simple letrozole-poloxamer188-PLLA co-solution electrospinning and used as subcutaneous implants to sustained release letrozole. Contents of poloxamer188 and letrozole were varied to investigate the effect of the two compounds' amounts on drug release behavior. Materials' combination and drug incorporation in fibers were investigated by X-ray diffraction and differential thermal calorimetry. Letrozole contents in vitro and in vivo were all determined by high-performance liquid chromatography-ultraviolet spectrometry. Meanwhile, in order to analyze the mechanism of drug release behavior and show modulated drug release by electrospun fibers, letrozole-poloxamer188 solid dispersions (SDs) and letrozole-poloxamer188poly L-lactic acid-dichloromethane solution cast films (CFs) were also studied. Plasma letrozole concentration curves of subcutaneous implanting EFNW and daily oral administration of poloxamer188-letrozole SD on female rabbits were investigated and compared. Fibers of desirable morphology were obtained. During the whole release process of all EFNWs, water-insoluble letrozole could be released in the form of being dissolved. Letrozole release rates increased with increasing poloxamer188 content and decreased with increasing letrozole content. When letrozole and poloxamer188 content in fibers was 30% and 150% (EFNW-30-150%), respectively (with respect to PLLA in mass ratio), the release curve presented a desirable profile. After subcutaneous implant of EFNW-30-150%, the plasma concentration curve presented a later peak time and lower maximum value, and a comparable bioavailability with daily oral administration of poloxamer188-letrozole SD solution within 15 days. The research provided primary and encouraging information to use EFNW as a novel subcutaneous implant for sustained delivery of water-insoluble drugs. [ABSTRACT FROM AUTHOR]

Here we report the application of solid dispersion (SD) technique to improve paclitaxel (PTX) release from poly(ε-caprolactone) (PCL)-based film. Paclitaxel solid dispersions (SDs) with either poloxamer188 (PXM) or polyethylene glycol (PEG) were successfully prepared by a melting method and then incorporated into PCL films, which were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and In vitro drug release/dissolution studies. It was found that PTX was faster released from the SDs than the corresponding physical mixtures (PMs) or PTX alone. For the PCL films with almost the same PTX loading, drug release from films containing SDs was remarkably faster than that from the film directly incorporated with PTX particles, and the films containing SDs with PXM exhibited a faster drug release than those with PEG. An increase In the content of PXM had no significant influence on PTX release from the films containing SDs. Incorporation of a higher content of SDs led to slower drug release from PCL films, indicating that PTX loading had a dominating effect on drug release. Through this study, we demonstrated the feasibility of the application of SD technique on the improvement of PTX release from PCL films and offered some beneficial information on modulating drug release behavior by changing the compositions and contents of the SDs-loaded PCL films. [ABSTRACT FROM AUTHOR]

Domperidone is a highly water insoluble drug exhibiting poor dissolution pattern. The purpose of this work was to increase the dissolution rate of Domperidone by formation of solid dispersion with different water soluble carriers. Binary systems of Domperidone were prepared with polyvinyl pyrrolidone k-30 (PVP), poloxamer 188 (P188) and polyethylene glycol 6000 (PEG 6000) at different weight ratios using the solvent evaporation method, physical mixtures of the same systems were also used. The effect of the method of preparation was also investigated by preparing some selected formulations using melting method. As P188 is known to inhibit CYP3A4 enzyme which is responsible for hepatic metabolism of many drugs including Domperidone, the effect of incorporation of PVP or PEG 6000 as ternary component to P188 solid dispersion on dissolution rate was also investigated. Formulations were characterized by Fourier transform infrared (FTIR) and Differential scanning calorimetry (DSC). Drug content uniformity and dissolution rate were studied. Solid dispersions showed a better dissolution compared to the pure drug and physical mixtures, with PVP showing the highest dissolution efficiency. As indicated from DSC data, Domperidone was in the amorphous form, which confirmed the better dissolution rate of solid dispersions. Some ternary P188 combinations showed a better enhancement in drug dissolution compared to the optimized P188 binary system. This would present a potential of increasing oral bioavailability of Domperidone by increasing its dissolution rate and by inhibiting its presystemic metabolism by the presence of P188. [ABSTRACT FROM AUTHOR]

Poloxamer188 (PL188), as one of the most commonly used pharmaceutical excipients, has unique physicochemical properties and good biocompatibility, and so is playing an increasingly extensive role in the field of medicine. Currently, there are few studies on the tissue distribution of PL188 in vivo. In this study, the LC-MS method based on MSALL technique of quadrupole time of flight mass spectrometry for absolute quantitative analysis of poloxamer 188 in biological substrates was established for the first time. The tissue distribution of poloxamer188 in SD rats were studied using the established quantitative analysis method. To explore the distribution of PL188 in organs and tissues, PL188 was administered via rat tail vein at a dose of 5 mg/kg. Eight kinds of tissues including heart, liver, spleen, lung, kidney, stomach, muscle and brain of rats were collected at 0.25 h, 1 h and 4 h after administration. Tissue distributions showed the highest level was observed in kidney, then in stomach, which indicated PL188 mainly bioaccumulated in the kidney. This study can provide references for the further study of PL188. [ABSTRACT FROM AUTHOR]

Poloxamer (PL)188 is a commonly used pharmaceutical excipient with unique physicochemical properties. In this study, an MS ALL quantitative method for the determination of PL188 in rat plasma by UHPLC-Q-TOF/MS was developed and validated. PL188 was analyzed on PLRP-S reversed-phase column (50 × 4.6 mm, 8 μm, 1,000 Å) with mobile phase 0.1% formic acid-water and 0.1% formic acid in acetonitrile-isopropanol (2:3, v/v). The liner range was 0.1-10.0 μg/ml. A pharmacokinetic study was performed on rats at a dose of 5 mg/kg by intravenous injection. The pharmacokinetic parameters of intravenous injection were as follows: half-life was 2.0 ± 1.1 h, volume of distribution was 5.1 ± 3.2 L/kg, area under the concentration-time curve was 3.0 ± 0.6 μg/L h and clearance was 1.7 ± 0.3 L/h/kg. The results indicated that PL188 could be rapidly distributed to tissues with a high clearance rate. This study can provide a good reference for the further study of PL188., (© 2021 John Wiley & Sons, Ltd.)

The objective of this study was to enhance dissolution and permeation of a low soluble, absorbable fexofenadine hydrochloride (FFH) by preparing solid dispersions using polyethylene glycol 20,000 (PEG 20,000) and poloxamer 188 as carriers. The phase solubility measurement for the supplied FFH revealed a linear increase in the solubility of fexofenadine with increasing carrier concentration in water (1.45 mg/mL to 11.78 mg/mL with 0% w/v to 30% w/v PEG 20,000; 1.45 mg/mL to 12.27 mg/mL with 0% w/v to 30% w/v poloxamer 188). To select the appropriate drug carrier concentration, a series of solid dispersions were prepared in the drug carrier weight ratios of 1:1, 1:2 and 1:4 by fusion method. The solid dispersions composed of drug carrier at 1:4 weight ratio showed highest dissolution with the time required for the release of 50% of the drug <15 min compared to the supplied FFH (>120 min). The intestinal absorption study presented a significant improvement in the absorption of drug from the solid dispersions composed of poloxamer 188 than PEG 20,000. In summary, the solid dispersions of FFH prepared using PEG 20,000 and poloxamer 188 demonstrated improved dissolution and absorption than supplied FFH and could be used to improve the oral bioavailability of fexofenadine. [ABSTRACT FROM AUTHOR]

Brusatol (Bru) exhibits promising anticancer effects, with both proliferation inhibition and chemoresistance amelioration activity. However, the poor solubility and insufficient intracellular delivery of Bru greatly restrict its application. Herein, to simultaneously utilize the advantages of Pluronics as drug carriers and tumor microenvironment-responsive drug release profiles, a flexible amphiphilic copolymer with a polymer skeleton, that is, Pluronic ® F68 grafting with linoleic acid moieties by redox-reducible disulfide bonds (F68-SS-LA), was synthesized. After characterization by 1 H-nuclear magnetic resonance and Fourier transform infrared spectroscopy, the redox-sensitive F68-SS-LA micelles were self-assembled in a much lower critical micelle concentration than that of the unmodified F68 copolymer. Bru was loaded in micelles (Bru/SS-M) with high loading efficiency, narrow size distribution, and excellent storage stability. The redox-sensitive Bru/SS-M exhibited rapid particle dissociation and drug release in response to a redox environment. Based on the enhanced cellular internalization, Bru/SS-M achieved higher cytotoxicity in both Bel-7402 and MCF-7 cells compared with free Bru and nonreducible micelles. The improved anticancer effect was attributed to the remarkably decreased mitochondrial membrane potential and increased reactive oxygen species level as well as apoptotic rate. These results demonstrated that F68-SS-LA micelles possess great potential as an efficient delivery vehicle for Bru to promote its anticancer efficiency via an oxidation pathway., Competing Interests: Disclosure The authors report no conflicts of interest in this work.