Spectroscopic characterization and pharmacokinetic evaluation of amorphous solid dispersions of glibenclamide for bioavailability enhancement in Wistar rats.

Oral bioavailability of glibenclamide (Glb) was appreciably improved by the formation of an amorphous solid dispersion with Poloxamer-188 (P-188). Poloxamer-188 substantially enhanced the solubility and thereby the dissolution rate of the biopharmaceutics classification system (BCS) class II drug Glb and simultaneously exhibited a better stabilizing effect of the amorphous solid dispersion prepared by the solvent evaporation method. The physical state of the dispersed Glb in the polymeric matrix was characterized by differential scanning calorimetry, X-ray diffraction, scanning electron microscope and Fourier transform infrared studies. In vitro drug release in buffer (pH 7.2) revealed that the amorphous solid dispersion at a Glb-P-188 ratio of 1:6 (SDE4) improved the dissolution of Glb by 90% within 3 h. A pharmacokinetic study of the solid dispersion formulation SDE4 in Wistar rats showed that the oral bioavailability of the drug was greatly increased as compared with the market tablet formulation, Daonil®. The formulation SDE4 resulted in an AUC0-24h ~2-fold higher. The SDE4 formulation was found to be stable during the study period of 6 months.

P188 Therapy in In Vitro Models of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant cause of morbidity and mortality worldwide. Varied mechanisms of injury contribute to the heterogeneity of this patient population as demonstrated by the multiple published grading scales and diverse required criteria leading to diagnoses from mild to severe. TBI pathophysiology is classically separated into a primary injury that is characterized by local tissue destruction as a result of the initial blow, followed by a secondary phase of injury constituted by a score of incompletely understood cellular processes including reperfusion injury, disruption to the blood-brain barrier, excitotoxicity, and metabolic dysregulation. There are currently no effective pharmacological treatments in the wide-spread use for TBI, in large part due to challenges associated with the development of clinically representative in vitro and in vivo models. Poloxamer 188 (P188), a Food and Drug Administration-approved amphiphilic triblock copolymer embeds itself into the plasma membrane of damaged cells. P188 has been shown to have neuroprotective properties on various cell types. The objective of this review is to provide a summary of the current literature on in vitro models of TBI treated with P188.

Evaluating the Efficacy of Combined P188 Treatment and Surgical Intervention in Preventing Post-Traumatic Osteoarthritis Following a Traumatic Knee Injury.

Previous studies have shown that reconstructive surgery alone following injury to the anterior cruciate ligament (ACL) does not prevent the development of post-traumatic osteoarthritis (PTOA). Poloxamer 188 (P188) has been shown to prevent cell death following trauma in both articular cartilage and meniscal tissue. This study aims to test the efficacy of single or multiple administrations of P188 in conjunction with reconstructive surgery to help prevent or delay the onset of the disease. Thirty skeletally mature rabbits underwent closed-joint trauma that resulted in ACL rupture and meniscal damage and were randomly assigned to one of four treatment groups with varying doses of P188. ACL reconstruction was then performed using an autograft from the semitendinosus tendon. Animals were euthanized 1-month following trauma, meniscal tissue was assessed for changes in morphology, mechanical properties, and proteoglycan content. Femurs and tibias were scanned using microcomputed tomography to determine changes in bone quality, architecture, and osteophyte formation. The medial meniscus experienced more damage and a decrease in the instantaneous modulus regardless of treatment group, while P188 treatment tended to limit degenerative changes in the lateral meniscus. Both lateral and medial menisci had documented decreases in the equilibrium modulus and inconsistent changes in proteoglycan content. Minimal changes were documented in the tibias and femurs, with the only significant change being the formation of osteophytes in both bones regardless of treatment group. The data suggest that P188 was able to limit some degenerative changes in the meniscus associated with PTOA and may warrant future studies.

A MSALL quantitative method for the determination of Poloxamer 188 in rat plasma by UHPLC-Q-TOF/MS and its application to pharmacokinetic study.

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.

Enhancement of the dissolution and in-vitro activity of a new antineoplastic agent.

The cell-surface molecule CD44 plays a major role in the regulation of cancer stem cells. The CD44 inhibitor compound N'-(1-dimethylaminomethyl-2-oxoindolin-3-ylidene)-2-(benzyloxy)benzohydrazide (OYB), anticancer agent is practically insoluble in water. Hence, the solid dispersion (SD) technique was used for enhancing the dissolution of OYB. The SD of OYB was achieved using OYB:poloxamer 188 (1:7) via the fusion method. The anticancer activities of the free-OYB solution and the SD formulation (OYB-SD) were investigated in-vitro. The dissolution rate of OYB-SD (1:7) increased by 2-fold compared with the untreated drug (51.52-100% at pH 1.2 and 8.25-19.15% at pH 7 buffer). In addition, OYB-SD afforded 3-folds cytotoxic effect, against LoVo cells, compared to the untreated compound (IC50 4.72 ± 0.57 and 13.97 ± 0.90 µg/ml, respectively) and against HepG2 (∼3-fold) (4.98 ± 0.368 and 13.85 ± 1.82 µg/ml, respectively) and MCF-7 (1.4-fold) cells (15.20 ± 0.20 and 21.12 ± 0.51 µg/ml, respectively), and enhanced the apoptotic potential in LoVo cells compared with free-OYB. The improved cytotoxic activity of the drug might be attributable to the enhanced dissolution of OYB.

One-Way Intestinal Perfusion of PVP/VA-Poloxamer 188-Curcuma longa L. Extract Solid Dispersion in Rats In Vivo and Its Effect on HSC-T6 Cell Proliferation.

Turmeric was the dried rhizome of Curcuma longa L., and its extract had important pharmacological effects such as anti-tumor, cholagogic, and antioxidant. However, curcuma extract had poor water solubility and low bioavailability, which had become the main limiting factor for its clinical application. The purpose of this study was to prepare PVP/VA-Poloxamer-188-curcuma extract solid dispersion (PAP-CSD) to improve the solubility and bioavailability of the curcuma extract. The intestinal absorption mechanism of solid dispersion of this extract was studied by one-way intestinal perfusion in rats. PAP-CSD,PVP/VA-curcuma extract solid dispersion (PA-CSD) and Poloxamer-188-curcuma extract solid dispersion (P-CSD) was able to improve the intestinal absorption of the curcuma extract (P < 0.05), and PAP-CSD (combined use of two carriers) was better than that of PA-CSD and P-CSD. CCK8 method was used to investigate the effects of the curcuma extract and PAP-CSD on the proliferation of hepatic stellate cells (HSC)-T6 cells. The inhibitory effect of PAP-CSD on the proliferation of HSC-T6 cells, related to the p38 MAPK pathway, was better than that of the curcuma extract.

Solid lipid nanoparticle as an effective drug delivery system of a novel curcumin derivative: formulation, release in vitro and pharmacokinetics in vivo.

CONTEXT: Curcumin (Cur) has a short duration of action which limits its therapeutic efficacy. Carbonic acid 17-(1,5-dimethyl-hexyl)-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl ester 4-[7-(4-hydroxy-3-methoxy-phenyl)-3,5-dioxo-hepta-1,6-dienyl]-2-methoxy-phenyl ester (CUD), as a small molecule derivative of Cur with superior stability, has been developed in our laboratory. OBJECTIVE: CUD-loaded solid lipid nanoparticles (CUD-SLN) were prepared to prolong the duration of the drug action of Cur. MATERIALS AND METHODS: CUD-SLN were prepared with Poloxamer 188 (F68) and hydrogenated soybean phospholipids (HSPC) as carriers, and the prescription was optimized. The in vitro release of CUD and CUD-SLN was investigated. CUD-SLN (5 mg/kg) was injected into Sprague Dawley (SD) rats to investigate its pharmacokinetic behaviour. RESULTS: CUD-SLN features high entrapment efficiency (96.8 ± 0.4%), uniform particle size (113.0 ± 0.8 nm), polydispersity index (PDI) (0.177 ± 0.007) and an appropriate drug loading capacity (6.2 ± 0.1%). Optimized CUD-SLN exhibited sustained release of CUD for about 48 h. Moreover, the results of the pharmacokinetic studies showed that, compared to Cur, CUD-SLN had a considerably prolonged half-life of 14.7 h, slowed its metabolism in vivo by 35.6-fold, and had an improved area under the curve (AUC0-t) of 37.0-fold. CONCLUSIONS: CUD-SLN is a promising preparation for the development of a small molecule derivative of Cur.

Poloxamer 188-Coated Ammonium Methacrylate Copolymer Nanocarriers Enhance Loperamide Permeability across Pgp-Expressing Epithelia.

Loperamide is a µ-opioid agonist with poor gastrointestinal absorption, mainly because of its modest aqueous solubility and being a P-glycoprotein (Pgp) efflux substrate. Nevertheless, studies associated with therapeutic effects strongly suggest that loperamide holds potential pharmacological advantages over traditional µ-opioid agonists commonly used for analgesia. Thus, in this Communication, we assessed in MDCK-hMDR1 cell lines the effects over loperamide uptake and efflux ratio, when loaded into Eudragit RS (ERS) nanocarriers coated with poloxamer 188 (P188). ERS was chosen for enhancing loperamide aqueous dispersibility and P188 as a potential negative Pgp modulator. In uptake assays, it was observed that Pgp limited the accumulation of loperamide into cells and that preincubation with P188, but not coincubation, led to increasing loperamide uptake at a similar extent of Pgp pharmacological inhibition. On the other hand, the efflux ratio displayed no alterations when Pgp was pharmacologically inhibited, whereas ERS/P188 nanocarriers effectively enhanced loperamide uptake and absorptive transepithelial transport. The latter suggests that loperamide transport across cells is significantly influenced by the presence of the unstirred water layer (UWL), which could hinder the visualization of Pgp-efflux effects during transport assays. Thus, results in this work highlight that formulating loperamide into this nanocarrier enhances its uptake and transport permeability.

Tissue Distribution Study of Poloxamer188 in Rats by Ultra-High-Performance Liquid Chromatography Quadrupole Time of Flight/Mass Spectrometry with MSALL-Based Approach.

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.

Preparation and Anti-tumor Study of Dextran 70,000-Selenium Nanoparticles and Poloxamer 188-Selenium Nanoparticles.

The anti-tumor effect of selenium nanoparticles (SeNPs) has received more and more attention. However, the clinical application of SeNPs is not optimistic due to the poor stability. To improve the stability of SeNPs, many polymers are used to modify the SeNPs. However, most of the polymers are not approved by FDA. It is significant to develop a SeNPs product with good stability for clinic application. Dextran 70,000 (T70) and poloxamer 188 (P188) are FDA-approved pharmaceutical injection excipients. In this study, we decorate SeNPs with T70 and P188 and assess the physicochemical characterization, storage stability, and anti-tumor activities of T70-SeNPs and P188-SeNPs. Transmission electron microscopy (TEM) shows that T70-SeNPs and P188-SeNPs are spherical particles with particle sizes of 110 nm and 60 nm respectively. Fourier-Transform Infrared Spectra (FT-IR) show that T70 or P188 can interact with SeNPs through hydrogen bonding. Stability study shows that P188-SeNPs freeze-dried powder and T70-SeNPs freeze-dried powder remain stable at 4℃ for 6 months. T70-SeNPs and P188-SeNPs can aggregate in cell matrix and play an anti-tumor role to HepG2 by promoting apoptosis, increasing reactive oxygen species (ROS) content and reducing mitochondrial membrane potential (MMP). This study can provide reference for industrial production of SeNPs products.

Formulation of amorphous ternary solid dispersions of dapagliflozin using PEG 6000 and Poloxamer 188: solid-state characterization, ex vivo study, and molecular simulation assessment.

The present study was designed to prepare dapagliflozin (DFG) loaded ternary solid dispersions (SDs) using the carrier blend polyethylene glycol 6000 (PEG 6000) and poloxamer 188 (PLX 188). The prepared DFG-SDs were evaluated for solubility study, physicochemical characterization and molecular simulation study. The prepared DFG-SDs showed significant higher solubility and dissolution vis-a-vis pure DFG and DFG physical mixture. The composition DFG:PEG:PLX (1:2.25:0.75 mM) showed the highest solubility (0.476 ± 0.016 mg/mL). The physicochemical characterization confirms the polymorphic transition of DFG from crystalline state to stable amorphous form. The prepared DFG-SDs showed a significantly higher dissolution (64.78 ± 2.34% to 78.41 ± 2.39%) than pure DFG (15.70 ± 3.54%). DFG-SD2 showed a significantly enhanced drug permeation (p<.05) (58.76 ± 4.65 µg/cm) as compared to pure DFG (14.97 ± 3.32 µg/cm). The molecular docking study result revealed a good hydrophobic interaction of DFG with the used carrier due to the lowest energy pose. The interaction occurs between the methylene bridges and the central hydrophobic chain of polyoxypropylene of the polymer. Therefore, DFG-SDs prepared by microwave irradiation method using hydrophilic carrier blend might be a promising strategy for improving the solubility and in vitro dissolution performance.

A comparison of different surfactants on foam stability in foam sclerotherapy in vitro.

OBJECTIVE: This article compares the effect of different surfactants on foam stability and determines the foam decay relationship, so that the suitability of surfactants in a clinical setting can be evaluated. METHODS: Five different surfactants were used to prepare sclerosing foam at room temperature using a liquid:gas ratio of 1:4 in vitro. Foam decay experiments were performed for each sample using a laboratory-made foaming apparatus, and the process was recorded using a video camera. The stability indices used included the drainage time, drainage rate, half-life, foam half-life volume, surfactant stability index, and foaming index. RESULTS: The sodium morrhuate foam was relatively more stable than the polidocanol foam, but exhibited weak foaming. After the addition of the surfactants, the foam half-life was less than 300 seconds. The effect of the surfactants on the stability of the sodium morrhuate foam was more pronounced. The surfactant stability indices could be arranged as follows: poloxamer 188 > Tween 80 > macrogol 4000 > propanediol > lecithin. However, the differences in the foaming indices were small. CONCLUSIONS: Of the five surfactants tested, poloxamer 188 has best performance to enhance sclerosing foam stability. The addition of the surfactants improved the stability of the sclerosing foams. It was observed that the relationships between the foam half-life and the surfactant stability index and the surfactant concentration follow the power law.

Heat Treatment of Poloxamer-Stabilized Triglyceride Nanodispersions: Effects and Underlying Mechanism.

Lipid nanoemulsions are being investigated for the parenteral administration of poorly soluble drugs. A narrow particle size distribution in these formulations is a prerequisite for meaningful research and safe administration to patients. Autoclaving a poloxamer-stabilized trimyristin nanoemulsion resulted in moderate particle growth and a strong decrease in particle size distribution width ( Göke , K. ; Roese , E. ; Arnold , A. ; Kuntsche , J. ; Bunjes , H. Mol. Pharmaceutics 2016 , 13 , 3187 . ). In this work, the critical parameters for such a change upon autoclaving poloxamer 188-stabilized lipid nanodispersions were investigated to elucidate the underlying mechanism. Nanodispersions of triglycerides with esterified fatty acid chain lengths from C8 to C18 were treated at different temperatures and for varying durations. The influence of a decrease in poloxamer 188's cloud point was tested by adding potassium chloride to the dispersions prior to autoclaving. The influence of poloxamer 188 concentration and of the type of emulsifier was investigated. The change in particle size and particle size distribution width upon heat treatment was analyzed by dynamic or static light scattering or differential scanning calorimetry. A short esterified fatty acid chain length of the triglycerides, high temperatures, and the addition of potassium chloride were key factors for particle growth up to emulsion break up, whereas the cloud point of poloxamer 188 was irrelevant. Sodium dodecyl sulfate and sucrose laurate had negative effects on emulsion stability during autoclaving. It was concluded that the increase in particle size and the decrease in particle size distribution widths upon heat treatment resulted from heat-accelerated Ostwald ripening and not from a coalescence-based process.

Extensive Diminution of Particle Size and Amorphization of a Crystalline Drug Attained by Eminent Technology of Solid Dispersion: A Comparative Study.

The present study emphasized on the use of solid dispersion technology to triumph over the drawbacks associated with the highly effective antihypertensive drug telmisartan using different polymers (poloxamer 188 and locust bean gum) and methods (modified solvent evaporation and lyophilization). It is based on the comparison between selected polymers and methods for enhancing solubility through particle size reduction. The results showed different profiles for particle size, solubility, and dissolution of formulated amorphous systems depicting the great influence of polymer/method used. The resulting amorphous solid dispersions were characterized using x-ray diffraction (XRD), differential scanning calorimetry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and particle size analysis. The optimized solid dispersion (TEL 19) prepared with modified locust bean gum using lyophilization technique showed reduced particle size of 184.5 ± 3.7 nm and utmost solubility of 702 ± 5.47 µg/mL in water, which is quite high as compared to the pure drug (≤1 µg/mL). This study showed that the appropriate selection of carrier may lead to the development of solid dispersion formulation with desired solubility and dissolution profiles. The optimized dispersion was later formulated into fast-dissolving tablets, and further optimization was done to obtain the tablets with desired properties.

Self-dispersible nanocrystals of albendazole produced by high pressure homogenization and spray-drying.

Albendazole (ABZ) is a broad-spectrum antiparasitic drug used in the treatment of human or animal infections. Although ABZ has shown a high efficacy for repeated doses in monogastric mammals, its low aqueous solubility leads to erratic bioavailability. The aim of this work was to optimize a procedure in order to obtain ABZ self-dispersible nanocrystals (SDNC) by combining high pressure homogenization (HPH) and spray-drying (SD). The material thus obtained was characterized and the variables affecting both the HPH and SD processes were studied. As expected, the homogenizing pressure and number of cycles influenced the final particle size, while the stabilizer concentration had a strong impact on SD output and redispersion of powders upon contact with water. ABZ SDNC were successfully obtained with high process yield and redispersibility. The characteristic peaks of ABZ were clearly identified in the X-ray patterns of the processed samples. A noticeable increase in the dissolution rate was observed in the aqueous environment.

Poloxamer-188 and citicoline provide neuronal membrane integrity and protect membrane stability in cortical spreading depression.

Under pathological conditions such as brain trauma, subarachnoid hemorrhage and stroke, cortical spreading depression (CSD) or peri-infarct depolarizations contribute to brain damage in animal models of neurological disorders as well as in human neurological diseases. CSD causes transient megachannel opening on the neuronal membrane, which may compromise neuronal survival under pathological conditions. Poloxamer-188 (P-188) and citicoline are neuroprotectants with membrane sealing properties. The aim of this study is to investigate the effect of P-188 and citicoline on the neuronal megachannel opening induced by CSD in the mouse brain. We have monitored megachannel opening with propidium iodide, a membrane impermeable fluorescent dye and, demonstrate that P-188 and citicoline strikingly decreased CSD-induced neuronal PI influx in cortex and hippocampal dentate gyrus. Therefore, these agents may be providing neuroprotection by blocking megachannel opening, which may be related to their membrane sealing action and warrant further investigation for treatment of traumatic brain injury and ischemic stroke.

Uncoupling of increased cellular oxidative stress and myocardial ischemia reperfusion injury by directed sarcolemma stabilization.

Myocardial ischemia/reperfusion (I/R) injury is a major clinical problem leading to cardiac dysfunction and myocyte death. It is widely held that I/R causes damage to membrane phospholipids, and is a significant mechanism of cardiac I/R injury. Molecular dissection of sarcolemmal damage in I/R, however, has been difficult to address experimentally. We studied here cardiac I/R injury under conditions targeting gain- or loss-of sarcolemma integrity. To implement gain-in-sarcolemma integrity during I/R, synthetic copolymer-based sarcolemmal stabilizers (CSS), including Poloxamer 188 (P188), were used as a tool to directly stabilize the sarcolemma. Consistent with the hypothesis of sarcolemmal stabilization, cellular markers of necrosis and apoptosis evident in untreated myocytes were fully blocked in sarcolemma stabilized myocytes. Unexpectedly, sarcolemmal stabilization of adult cardiac myocytes did not affect the status of myocyte-generated oxidants or lipid peroxidation in two independent assays. We also investigated the loss of sarcolemmal integrity using two independent genetic mouse models, dystrophin-deficient mdx or dysferlin knockout (Dysf KO) mice. Both models of sarcolemmal loss-of-function were severely affected by I/R injury ex vivo, and this was lessened by CSS. In vivo studies also showed that infarct size was significantly reduced in CSS-treated hearts. Mechanistically, these findings support a model whereby I/R-mediated increased myocyte oxidative stress is uncoupled from myocyte injury. Because the sarcolemma stabilizers used here do not transit across the myocyte membrane this is evidence that intracellular targets of oxidants are not sufficiently altered to affect cell death when sarcolemma integrity is preserved by synthetic stabilizers. These findings, in turn, suggest that sarcolemma destabilization, and consequent Ca(2+) mishandling, as a focal initiating mechanism underlying myocardial I/R injury.

Development of solid lipid microparticles (SLMs) containing asiatic acid for topical treatment of acne: Characterization, stability, in vitro and in vivo anti-acne assessment.

Solid lipid microparticles (SLMs) represent a promising approach for drug delivery in anti-acne applications. In this study, asiatic acid-loaded SLMs (AASLMs) were prepared by melt emulsification method in conjunction with freeze-drying. Comprehensive evaluations comprised particle size, %entrapment efficiency (%EE), %labeled amount (%LA), surface morphology, stability, %release, %skin permeation, and anti-acne activity. The AASLMs exhibited an average particle size ranging from 7.46 to 38.86 µm, with %EE and %LA falling within the range of 31.56 to 100.00 and 90.43 to 95.38, respectively. The AASLMs demonstrated a spherical shape under scanning electron microscopy, and maintained stability over a 3-month period. Notably, formulations with 10 % and 15 % cetyl alcohol stabilized with poloxamer-188 (specifically F6 and F12) displayed a minimum inhibitory concentration (MIC) value of 75 mg/ml against Cutibacterium acnes. Furthermore, F12 exhibited a higher %release and %skin permeation compared to F6 over 24 h. In a single-blind clinical trial involving fifteen participants with mild-to-moderate acne, F12 showcased its potential not only in reducing porphyrin intensity and enhancing skin barriers but also in significantly improving skin hydration and brightness. However, further investigations with larger subject cohorts encompassing diverse age groups and genders are necessary to thoroughly establish the performance of the developed AASLMs.

Combination chemotherapy via poloxamer 188 surface-modified PLGA nanoparticles that traverse the blood-brain-barrier in a glioblastoma model.

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.