Investigating the Effect of Surface Hydrophilicity on the Destiny of PLGA-Poloxamer Nanoparticles in an In Vivo Animal Model.

This study aimed to examine the impact of different surface properties of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (P NPs) and PLGA-Poloxamer nanoparticles (PP NPs) on their in vivo biodistribution. For this purpose, NPs were formulated via nanoprecipitation and loaded with diphenylhexatriene (DPH), a fluorescent dye. The obtained NPs underwent comprehensive characterization, encompassing their morphology, technological attributes, DPH release rate, and thermodynamic properties. The produced NPs were then administered to wild-type mice via intraperitoneal injection, and, at scheduled time intervals, the animals were euthanized. Blood samples, as well as the liver, lungs, and kidneys, were extracted for histological examination and biodistribution analysis. The findings of this investigation revealed that the presence of poloxamers led to smaller NP sizes and induced partial crystallinity in the NPs. The biodistribution and histological results from in vivo experiments evidenced that both, P and PP NPs, exhibited comparable concentrations in the bloodstream, while P NPs could not be detected in the other organs examined. Conversely, PP NPs were primarily sequestered by the lungs and, to a lesser extent, by the kidneys. Future research endeavors will focus on investigating the behavior of drug-loaded NPs in pathological animal models.

Study of the effect of active pharmaceutical ingredients of various classes of BCS on the parameters of thermosensitive systems based on poloxamers.

Introduction: The development of thermosensitive in situ systems has become widespread and prospective due to the optimal parameters of the phase transition - in the temperature range from room to physiological. Those properties can provide thermosensitive polymers, for example, poloxamers - as the most common.It is worth noting that the addition of active pharmaceutical ingredients (APIs) changes the parameters of in situ systems, but no systematic study of the effect of APIs has been conducted. The aim of this work was to develop a systematic approach to studying the effect of APIs on the in situ rheological properties of poloxamer compositions. Materials and methods: The biopharmaceutical classification system (BCS) was chosen as the basis. Accordingly, the following APIs were selected for the experiment: BCS class I - lidocaine hydrochloride and ketorolac tromethamine, class II - ibuprofen and diclofenac, class III - pyridoxine hydrochloride and ribavirin, class IV - furosemide and abiraterone. To create thermoreversible compositions, previously studied for stability combinations of poloxamer 407, poloxamer 188 and PEG 1500 were used.At the stage of preparation of experimental samples formulations with APIs of classes II and IV of BCS were excluded, since the solubilizing ability of poloxamers is not enough to obtain stable combined complexes. Results: In the course of the work, the following results were obtained: BCS class I APIs significantly reduced the phase transition temperature of the matrix of poloxamers 407 and 188, while the addition of PEG 1500 eliminated the effect of APIs on gels; BCS class III APIs practically did not affect the rheological properties of the studied combinations; the phase transition temperature of the gel based on poloxamer 407 did not change with the addition of Class I and Class III APIs.Nevertheless, the obtained results made it possible to reveal the regular behavior of in situ complexes of poloxamer matrices depending on the class of BCS of the API. Further research is required.

Microneedles assisted controlled and improved transdermal delivery of high molecular drugs via in situ forming depot thermoresponsive poloxamers gels in skin microchannels.

Skin is considered as an attractive route for variety of drug molecule administration. However, it is proved to be the main physical barrier for drug flux owing to their poor permeability and low bioavailability across stratum corneum layer. In the current study, novel approach has been used to enhance transdermal delivery via microporation through combination of poloxamers gels and microneedles (MNs) arrays. The phase transition of poloxamers at various concentrations from sol-gel was evaluated using AR2000 rheometer to confirm MNs-assisted in situ forming depots. Temperature test confirmed gelation between 32 and 37 °C. Curcumin was loaded in poloxamer formulations at variable concentrations and its effect showed reduction in critical gelation temperature (CGT) owing to its hydrophobic nature. Microneedle arrays (600 µm) prepared from Gantrez S-97, PEG10000 and gelatin B using (19 × 19) laser-engineered silicone micromoulds showed high mechanical stability investigated via Texture analyzer. From in situ dissolution profile, gelatin 15% w/w based MNs displayed quicker dissolution rate in comparison to PG10000. VivoSight® OCT scanner and dye tracking confirmed that PG10000 MNs arrays pierced SC layer, infiltrate the epidermis and goes to dermis layer. From in vitro permeation, it was concluded that 20% w/w PF127® gel formulations containing (0.1% and 0.3%) curcumin displayed high curcumin permeation for comparatively longer time through microporated skin samples in comparison to non-microporated skin. The curcumin distribution in skin tissues with higher florescence intensity was noted in MNs treated skin samples by confocal microscopy. FTIR confirmed the structure formation of fabricated MNs, while TGA showed dry, brittle and rigid nature of gelatin MNs.

Molecular Dynamics-Assisted Design of High Temperature-Resistant Polyacrylamide/Poloxamer Interpenetrating Network Hydrogels.

Polyacrylamide has promising applications in a wide variety of fields. However, conventional polyacrylamide is prone to hydrolysis and thermal degradation under high temperature conditions, resulting in a decrease in solution viscosity with increasing temperature, which limits its practical effect. Herein, combining molecular dynamics and practical experiments, we explored a facile and fast mixing strategy to enhance the thermal stability of polyacrylamide by adding common poloxamers to form the interpenetrating network hydrogel. The blending model of three synthetic polyacrylamides (cationic, anionic, and nonionic) and poloxamers was first established, and then the interaction process between them was simulated by all-atom molecular dynamics. In the results, it was found that the hydrogen bonding between the amide groups on all polymers and the oxygen-containing groups (ether and hydroxyl groups) on poloxamers is very strong, which may be the key to improve the high temperature resistance of the hydrogel. Subsequent rheological tests also showed that poloxamers can indeed significantly improve the stability and viscosity of nonionic polyacrylamide containing only amide groups at high temperatures and can maintain a high viscosity of 3550 mPa·S at 80 °C. Transmission electron microscopy further showed that the nonionic polyacrylamide/poloxamer mixture further formed an interpenetrating network structure. In addition, the Fourier transform infrared test also proved the existence of strong hydrogen bonding between the two polymers. This work provides a useful idea for improving the properties of polyacrylamide, especially for the design of high temperature materials for physical blending.

Solubility and Permeability Enhancement of Oleanolic Acid by Solid Dispersion in Poloxamers and γ-CD.

Oleanolic acid (OA) is a pentacyclic triterpenoid widely found in the Oleaceae family, and it represents 3.5% of the dry weight of olive leaves. OA has many pharmacological activities, such as hepatoprotection, anti-inflammatory, anti-oxidant, anti-diabetic, anti-tumor, and anti-microbic activities. Its therapeutic application is limited by its poor water solubility, bioavailability, and permeability. In this study, solid dispersions (SDs) were developed to overcome these OA limitations. Solubility studies were conducted to evaluate different hydrophilic polymers, drug-to-polymer ratios, and preparation methods. Poloxamer 188, Poloxamer 407, and γ-CD exhibited the highest increases in terms of OA solubility, regardless of the method of preparation. Binary systems were characterized using differential scanning calorimetry (DSC), X-ray diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). In addition, pure compounds and SDs were analyzed using scanning electron microscopy (SEM) in order to observe both the morphology and the particle surface. In vitro dissolution studies were performed for P407, P188, and γ-CD SDs. Preparation using the solvent evaporation method (SEM) produced the highest increase in the dissolution profiles of all three polymers with respect to the OA solution. Finally, the effect of SDs on OA permeability was evaluated with an in vitro parallel artificial membrane permeability assay (PAMPA). The formulation improved passive permeation across the simulated barrier due to OA increased solubility. The dissolution and PAMPA results indicate that the amorphization of OA by SD preparation could be a useful method to enhance its oral absorption, and it is also applicable on an industrial scale.

Multiple poloxamers increase plasma membrane repair capacity in muscle and nonmuscle cells.

Various previous studies established that the amphiphilic tri-block copolymer known as poloxamer 188 (P188) or Pluronic-F68 can stabilize the plasma membrane following a variety of injuries to multiple mammalian cell types. This characteristic led to proposals for the use of P188 as a therapeutic treatment for various disease states, including muscular dystrophy. Previous studies suggest that P188 increases plasma membrane integrity by resealing plasma membrane disruptions through its affinity for the hydrophobic lipid chains on the lipid bilayer. P188 is one of a large family of copolymers that share the same basic tri-block structure consisting of a middle hydrophobic propylene oxide segment flanked by two hydrophilic ethylene oxide moieties [poly(ethylene oxide)80-poly(propylene oxide)27-poly(ethylene oxide)80]. Despite the similarities of P188 to the other poloxamers in this chemical family, there has been little investigation into the membrane-resealing properties of these other poloxamers. In this study we assessed the resealing properties of poloxamers P181, P124, P182, P234, P108, P407, and P338 on human embryonic kidney 293 (HEK293) cells and isolated muscle from the mdx mouse model of Duchenne muscular dystrophy. Cell membrane injuries from glass bead wounding and multiphoton laser injury show that the majority of poloxamers in our panel improved the plasma membrane resealing of both HEK293 cells and dystrophic muscle fibers. These findings indicate that many tri-block copolymers share characteristics that can increase plasma membrane resealing and that identification of these shared characteristics could help guide design of future therapeutic approaches.

Evaluation of Budesonide-Hydroxypropyl-ß-Cyclodextrin Inclusion Complex in Thermoreversible Gels for Ulcerative Colitis.

BACKGROUND: New formulations for topical treatment of ulcerative colitis with budesonide inclusion complex (BUDHP-ß-CD) and poloxamers (PL) were developed for future clinical use. AIMS: This study evaluated the efficacy of such novel formulations in a rat model of colitis. METHODS: The PL-BUDHP-ß-CD systems were prepared by direct dispersion of the complex (BUD concentration 0.5 mg mL-1) in solutions with PL407 or PL403. Male Wistar rats underwent TNBS-induced colitis and were treated for 5 days by a rectal route, as follows: BUD 1: BUDHP-ß-CD + PL407 (18%); BUD 2: BUDHP-ß-CD + PL407 (20%); BUD 3: BUDHP-ß-CD + PL407 (18%) + PL403 (2%); BUD 4: plain BUD; BUD 5: BUDHP-ß-CD; C1: HP-ß-CD + PL407 (18%); C2: HP-ß-CD + PL407 (20%); C3: HP-ß-CD + PL407 (18%) + PL403 (2%); C4: saline. A negative control group without colitis was also used. Colitis was assessed via myeloperoxidase (MPO) activity, and macroscopic and microscopic damage score in colon tissues. Protein levels of TNF-α, IL-1ß, IL-10 and endogenous glucocorticoids were obtained using ELISA. RESULTS: BUDHP-ß-CD poloxamer formulations had similar MPO activity when compared with the negative control group. All formulations presented lower MPO activity than BUDHP-ß-CD and plain BUD (p < 0.001). BUD 2 produced lower microscopic score values than plain BUD and BUDHP-ß-CD (p < 0.01). All formulations with BUDHP-ß-CD poloxamers reduced TNF-α levels (p < 0.05). CONCLUSION: Novel budesonide inclusion complex formulations improved microscopic damage and reduced colonic MPO activity and TNF-α levels.

Thermoresponsive sol-gel improves ocular bioavailability of Dipivefrin hydrochloride and potentially reduces the elevated intraocular pressure in vivo.

The present study involves the development of Dipivefrin hydrochloride (DV) containing Poloxamers (P407 and P188)-Carbopol-934 (CP) based thermoresponsive-gels for the management of elevated intraocular pressure (IOP). Optimal formulation was evaluated for gelation temperature (Tgel), physicochemical and viscoelastic properties, in-vitro gel dissolution and drug release studies. The in-vivo safety, precorneal retention, ocular pharmacokinetics and efficacy in reducing IOP were also evaluated. Tgel of DV-containing thermoresponsive-gels were between 35.1 and 38.9 °C and it was Poloxamers and CP concentrations dependent. The optimal formulation (F8), composed of 20% P407, 5% P188 and 0.15% CP (w/v), had a Tgel of 35 °C. Its viscosity indicated good flow at room temperature and ability to convert to gel at ocular temperature and the rheology studies revealed favorable characteristics for its ocular use. In precorneal retention experiment, F8 indicated significantly higher area under concentrations curves as compared to DV-aqueous suspension (DV-AqS). In-vivo ocular pharmacokinetics indicated a significant improvement in ophthalmic bioavailability of epinephrine (active form of DV). F8 was non-irritant to the eyes and showed a successful, continuous and superior ability to reduce IOP compared to DV-AqS in rabbits. In conclusion, our developed system could be an appropriate substitute to the conventional DV eye preparations in the management of elevated IOP.

Nanotheranostic Pluronic-Like Polymeric Micelles: Shedding Light into the Dark Shadows of Tumors.

Cancer is a leading cause of death worldwide. Despite the advances in prevention, detection, diagnosis, and treatment, many tumors relapse and become resistant to conventional treatments. Theranostics and real-time molecular imaging using nanoscale materials, such as polymeric micelles, are being widely explored as promising gold standard approaches in a personalized medicine perspective for cancer. Theranostics is intended for the three-in-one purpose of simultaneously diagnose, treat, and monitor tumor evolution. Compared to the conventional treatments, theranostic functional polymeric micelles have demonstrated great potential to improve and monitor the delivery of pharmacological agents following administration, which can enhance therapeutic efficacy and minimize off-target toxicity. This review provides an overview of the current state of the art related to the use of polymeric micelles as theranostic multicarriers targeting the cancer cells and tumor microenvironment. Some future directions toward the design of nanotheranostic platforms are also proposed. In particular, we focused our attention on Pluronics and Tetronics as they advantageously present sol-gel transition, which makes them smart nanosystems suitable for oral theranostic administration and sustained depots, increasing patient compliance.

Reverse Phase Compatible TLC-Bioautography for Detection of Tyrosinase Inhibitors.

INTRODUCTION: Reverse phase chromatography and bioautographic assays are key tools for natural product bioguided isolation; however, their direct coupling has not been fully achieved. OBJECTIVES: To develop a bioautographic assay to detect tyrosinase inhibitors present in complex matrices sorbed on reverse phase (RP) TLC-plates that can be used for bioguided isolation of bioactive compounds. METHODS: Enzyme gel entrapment with an amphiphilic copolymer was used for assay development. The gel turns into a brown "skin like" colour due to tyrosinase catalysed oxidation of l-tyrosine. The inhibitors are visualised as clear spots against a brown coloured background. RESULTS: The assay was able to localise cinnamaldehyde in Cinnamomum cassia essential oil, as its main constituent with known tyrosinase inhibition properties. The assay allowed the detection of 0.03% (w/w) of kojic acid co-spotted with a methanolic extract of Sphaeralcea bonariensis and chromatographed on RP-TLC. CONCLUSION: The developed assay is able to detect, with high sensitivity, tyrosinase inhibitors present in complex matrices that were chromatographed in RP-TLC. Results can be easily read by colour change, inhibitors appear as clear spots in a darker background. Copyright © 2016 John Wiley & Sons, Ltd.

Preparation, characterization and biocompatibility studies of thermoresponsive eyedrops based on the combination of nanostructured lipid carriers (NLC) and the polymer Pluronic F-127 for controlled delivery of ibuprofen.

CONTEXT: Nanostructured lipid carrier (NLC) dispersions present low viscosity and poor mucoadhesive properties, which reduce the pre-corneal residence time and consequently, the bioavailability of ocular drugs. OBJECTIVE: The aim of this study was to prepare thermoresponsive eyedrops based on the combination of lipid nanoparticles and a thermoresponsive polymer with mucomimetic properties (Pluronic® F-127). MATERIALS AND METHODS: NLCi dispersions were prepared based on the melt-emulsification and ultrasonication technique. Physicochemical and morphological characteristics of the colloidal dispersions were evaluated. The formulation was also investigated for potential cytotoxicity in Y-79 human retinoblastoma cells and the in vitro drug release profile of the ibuprofen was determined. RESULTS: NLCi showed a Z-average below 200 nm, a highly positive zeta potential and an efficiency of encapsulation (EE) of ∼90%. The gelification of the NLCi dispersion with 15% (w/w) Pluronic® F-127 did not cause significant changes to the physicochemical properties. The potential NLC-induced cytotoxicity was evaluated by the Alamar Blue reduction assay in Y-79 cells, and no relevant cytotoxicity was observed after exposure to 0-100 µg/mL NLC for up to 72 hours. The optimized formulations showed a sustained release of ibuprofen over several hours. DISCUSSION AND CONCLUSION: The strategy proposed in this work can be successfully used to increase the bioavailability and the therapeutic efficacy of conventional eyedrops.

Enhancement of chlorpromazine antitumor activity by Pluronics F127/L81 nanostructured system against human multidrug resistant leukemia.

The development of specific tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia (CML). However, chemoresistance of tumor cells to TKIs has already been described, and several mechanisms account for the multidrug resistance (MDR) phenotypes, including the overexpression of P-glycoprotein (P-gp). This decreases the rate of healing and complete tumor remission. Nanotechnological tools have been studied to allow advances in this field. Poloxamers (Pluronics(®)) have been proposed as drug carriers to improve therapeutic efficacy and decrease side effects, even in cancer therapy, due to their ability to inhibit P-gp. Antipsychotic phenothiazines have been described as potent cytotoxic drugs against several types of tumor cells in vitro. Here, we show that nanostructured micellar systems containing the phenothiazine derivative chlorpromazine (CPZ) potentiated the cytotoxicity of free CPZ and increased the selectivity against CML tumor cells, demonstrating the pharmacological potential of these poloxamer-based nanostructured systems containing CPZ in cancer therapy.

Acid-Labile Amphiphilic PEO-b-PPO-b-PEO Copolymers: Degradable Poloxamer Analogs.

Poly ((ethylene oxide)-b-(propylene oxide)-b-(ethylene oxide)) triblock copolymers commonly known as poloxamers or Pluronics constitute an important class of nonionic, biocompatible surfactants. Here, a method is reported to incorporate two acid-labile acetal moieties in the backbone of poloxamers to generate acid-cleavable nonionic surfactants. Poly(propylene oxide) is functionalized by means of an acetate-protected vinyl ether to introduce acetal units. Three cleavable PEO-PPO-PEO triblock copolymers (Mn,total = 6600, 8000, 9150 g·mol(-1) ; Mn,PEO = 2200, 3600, 4750 g·mol(-1) ) have been synthesized using anionic ring-opening polymerization. The amphiphilic copolymers exhibit narrow molecular weight distributions (Ð = 1.06-1.08). Surface tension measurements reveal surface-active behavior in aqueous solution comparable to established noncleavable poloxamers. Complete hydrolysis of the labile junctions after acidic treatment is verified by size exclusion chromatography. The block copolymers have been employed as surfactants in a miniemulsion polymerization to generate polystyrene (PS) nanoparticles with mean diameters of ≈200 nm and narrow size distribution, as determined by dynamic light scattering and scanning electron microscopy. Acid-triggered precipitation facilitates removal of surfactant fragments from the nanoparticles, which simplifies purification and enables nanoparticle precipitation "on demand."

Effect of several PEO-PPO amphiphiles on bax, bcl-2, and hTERT mRNAs: An insight into apoptosis and cell immortalization induced in hepatoma cells by these polymeric excipients.

UNLABELLED: Recent data have shown that synthetic polymers and nanomaterials display phenotypic effects in cells and signal transduction mechanisms involved in inflammation, differentiation, proliferation, and apoptosis. AIM: This article aims to investigate the effect of poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) block copolymers with a wide range of biomedical and pharmaceutical applications on apoptosis and/or cell immortalization, by flow cytometry and multiplex RT-PCR for bax, bcl-2, and human telomerase reverse transcriptase (hTERT). RESULTS: PEO-PPO amphiphiles upregulated bax and hTERT and induced apoptosis of two human hepatoma cell lines. CONCLUSIONS: PEO-PPO block copolymers-considered safe for human use-can drastically alter gene expression profiles of genes related to apoptosis/cell proliferation.

Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions.

This study investigates the potential of poloxamers as solid dispersions (SDs) carriers in improving the dissolution rate of a poorly soluble drug, carbamazepine (CBZ). Solid dispersions were prepared with poloxamer 188 (P188) and poloxamer 407 (P407) by melting method in different drug:carrier ratios (1:1, 1:2 and 1:3). Prepared samples were characterized using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (HSM), powder X-ray diffraction (PXRD) and Fourier transform infrared spectroscopy (FT-IR) to investigate drug physical state within the SDs matrix, possible polymorphic transitions and drug-polymer interactions. The interactions between CBZ molecules and polymeric chains were also evaluated using molecular dynamics simulation (MDS) technique. The most thermodynamically stable polymorphic form III of CBZ was present in all SDs, regardless of the type of poloxamer and drug-to-carrier ratio. The absence of drug-polymer interactions was observed by FT-IR analysis and additionally confirmed by MDS. Formation of persistent hydrogen bond between two CBZ molecules, observed by MDS indicate high tendency of CBZ molecules to aggregate and form crystalline phase within dispersion. P188 exhibit higher efficiency in increasing CBZ dissolution rate due to its more pronounced hydrophilic properties, while increasing poloxamers concentration resulted in decreasing drug release rate, as a consequence of their thermoreversible gelation.

A reversed-phase compatible thin-layer chromatography autography for the detection of acetylcholinesterase inhibitors.

A dual readout autographic assay to detect acetylcholinesterase inhibitors present in complex matrices adsorbed on reversed-phase or normal-phase thin-layer chromatography plates is described. Enzyme gel entrapment with an amphiphilic copolymer was used for assay development. The effects of substrate and enzyme concentrations, pH, incubation time, and incubation temperature on the sensitivity and the detection limit of the assay were evaluated. Experimental design and response surface methodology were used to optimize conditions with a minimum number of experiments. The assay allowed the detection of 0.01% w/w of physostigmine in both a spiked Sonchus oleraceus L. extract chromatographed on normal phase and a spiked Pimenta racemosa (Mill.) J.W. Moore leaf essential oil chromatographed on reversed phase. Finally, the reversed-phase thin-layer chromatography assay was applied to reveal the presence of an inhibitor in the Cymbopogon citratus (DC.) Stapf essential oil. The developed assay is able to detect acetylcholinesterase inhibitors present in complex matrixes that were chromatographed in normal phase or reversed-phase thin-layer chromatography. The detection limit for physostigmine on both normal and reversed phase was of 1×10(-4) µg. The results can be read by a change in color and/or a change in fluorescence.

Phase transforming in situ gels for sustained and controlled transmucosal drug delivery via the intravaginal route.

Direct, reliable, controlled, and sustained drug delivery to female reproductive tract (FRT) remains elusive, with conventional dosage forms falling way short of the mark, leading to premature leakage, erratic drug delivery, and loss of compliance. Historically, the intravaginal route remains underserved by the pharmaceutical sector. To comprehensively address this, we turned our focus to phase-transforming sol-gels, using poloxamers, a thermosensitive polymer and, doxycycline (as hyclate salt, DOXH) as our model agent given its potential use in sexually transmitted infections (STIs). We further enhanced mucoadhesiveness through screening of differing viscosity grade hydroxypropyl methyl celluloses (HPMCs). The optimised sol-gels remained gelled at body temperature (<37 °C) and were prepared in buffer aligned to vaginal cavity pH and osmolality. Lead formulations were progressed based on their ability to retain key rheological properties, and acidic pH in the presence of simulated vaginal fluid (SVF). From a shelf-life perspective, DOXH stability, gelation temperature (Tsol-gel), and pH to three months (2-8 °C) was attained. In summary, the meticulously engineered, phase-transforming sol-gels provided sustained mucoretention despite dilution by vaginal fluid, paving the way for localised antimicrobial drug delivery at concentrations that potentially far exceed the minimum inhibitory concentration (MIC) for target STI-causing bacteria of the FRT.

Thermal Lens Measurements of Thermal Expansivity in Thermosensitive Polymer Solutions.

The weak absorption of a laser beam generates in a fluid an inhomogeneous refractive index profile acting as a negative lens. This self-effect on beam propagation, known as Thermal Lensing (TL), is extensively exploited in sensitive spectroscopic techniques, and in several all-optical methods for the assessment of thermo-optical properties of simple and complex fluids. Using the Lorentz-Lorenz equation, we show that the TL signal is directly proportional to the sample thermal expansivity α, a feature allowing minute density changes to be detected with high sensitivity in a tiny sample volume, using a simple optical scheme. We took advantage of this key result to investigate the compaction of PniPAM microgels occurring around their volume phase transition temperature, and the temperature-driven formation of poloxamer micelles. For both these different kinds of structural transitions, we observed a significant peak in the solute contribution to α, indicating a decrease in the overall solution density-rather counterintuitive evidence that can nevertheless be attributed to the dehydration of the polymer chains. Finally, we compare the novel method we propose with other techniques currently used to obtain specific volume changes.

Effects of Poloxamers as Excipients on the Physicomechanical Properties, Cellular Biocompatibility, and In Vitro Drug Release of Electrospun Polycaprolactone (PCL) Fibers.

Electrospun microfibers are emerging as one of the advanced wound dressing materials for acute and/or chronic wounds, especially with their ability to carry drugs and excipients at a high loading while being able to deliver them in a controlled manner. Various attempts were made to include excipients in electrospun microfibers as wound dressing materials, and one of them is poloxamer, an amphiphilic polymer that exhibits wound debridement characteristics. In this study, we formulated two types of poloxamers (i.e., P188 and P338) at 30% (w/w) loading into electrospun polycaprolactone (PCL) fibers to evaluate their physicomechanical properties, biocompatibility, and in vitro drug release of a model drug. Our findings showed that the incorporation of poloxamers in the PCL solutions during electrospinning resulted in a greater "whipping" process for a larger fiber deposition area. These fibers were mechanically stiffer and stronger, but less ductile as compared to the PCL control fibers. The incorporation of poloxamers into electrospun PCL fibers reduced the surface hydrophobicity of fibers according to our water contact angle studies and in vitro degradation studies. The fibers' mechanical properties returned to those of the PCL control groups after "dumping" the poloxamers. Moreover, poloxamer-loaded PCL fibers accelerated the in vitro release of the model drug due to surface wettability. These poloxamer-loaded PCL fibers were biocompatible, as validated by MTT assays using A549 cells. Overall, we demonstrated the ability to achieve a high loading of poloxamers in electrospun fibers for wound dressing applications. This work provided the basic scientific understanding of materials science and bioengineering with an emphasis on the engineering applications of advanced wound dressings.