In Vitro/In Vivo Correlation of Two Extended-Release Cilostazol Formulations.

This study aims to evaluate and determine the correlation between in vitro release and in vivo pharmacokinetics of two extended-release dosage forms of Cilostazol. In vitro release profiles for two dosage forms, tablet and capsule, were analyzed under physiologically mimicked medium conditions using the paddle and basket USP release apparatus. A single-dose, two-period crossover study design in beagle dogs was applied for the pharmacokinetic study. The fed and fast effects were considered for evaluation. Pseudo gastric release medium transfer setup study from pH 1.2 to pH 6.8 (+0.5% SLS) and pH 1.2 to pH 6.8 (+1.0% SLS) demonstrated that Pletaal® SR 200 mg capsules have higher drug release rates than Cilostan® CR 200 mg tablets. Similarly, in vivo study showed Cilostazol concentration in plasma and AUC was lower under the fast state than the fed state. The ratio of least squared geometric mean values, Cmax, AUC0-t, and AUC0-inf of Cilostazol were 2.53-fold, 2.89-fold, and 2.87-fold higher for Pletaal® SR 200 mg capsules compared with Cilostan® CR 200 mg tablets, respectively. Correlation of in vitro/in vivo data indicated that Pletal® SR 200 mg capsules have better release and pharmacodynamic effect than Cilostan® CR 200 mg tablets.

Genetically engineered long-acting Esculentin-2CHa(1-30) fusion protein with potential applicability for the treatment of NAFLD.

Esculentin-2CHa(1-30) (?ESC") has been reported as a potent anti-diabetic peptide with little toxicity. However, its very short plasma residence time severely limits the therapeutic efficacy. To address this issue, we genetically engineered a fusion protein of tandem trimeric ESC with an albumin binding domain (ABD) and a fusion partner, SUMO (named ?SUMO-3×ESC-ABD"). The SUMO-3×ESC-ABD, successfully produced from E. coli, showed low cellular and hemolytic toxicity while displaying potent activities for the amelioration of hyperglycemia as well as non-alcoholic fatty liver disease (NAFLD) in vitro. In animal studies, the estimated plasma half-life of SUMO-3×ESC-ABD was markedly longer (427-fold) than that of the ESC peptide. In virtue of the extended plasma residence, the SUMO-3×ESC-ABD could produce significant anti-hyperglycemic effects that lasted for >2 days, while both the ESC or ESC-ABD peptides elicited little effects. Further, twice-weekly treatment for 10 weeks, the SUMO-3×ESC-ABD displayed significant improvement in blood glucose control with a reduction in body weight. Most importantly, a significant improvement in the conditions of NAFLD was observed in the SUMO-3×ESC-ABD-treated mice. Along the systemic effects (by improved glucose tolerance and body weight reduction), direct inhibition of the hepatocyte lipid uptake was suggested as the major mechanism of the anti-NAFLD effects. Overall, this study demonstrated the utility of the long-acting SUMO-3×ESC-ABD as a potent drug candidate for the treatment of NAFLD.

Albumin-coated copper nanoparticles for photothermal cancer therapy: Synthesis and in vitro characterization.

Copper nanoparticles (CuNPs) have attracted great interest in various biomedical research fields due to their superior optical and plasmonic properties. In the present study, we synthesized bovine serum albumin (BSA)-coated CuNPs (BSA-CuNPs) by adopting the aqueous reduction method in 2-step procedures. The prepared BSA-CuNPs were characterized in vitro for their physical characteristics and photothermal activity. The successful synthesis of BSA-CuNPs was verified through transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and ultraviolet-visible (UV-VIS) light spectroscopy. The prepared BSA-CuNPs revealed a great light-to-heat conversion capacity and good photothermal stability. Notably, accompanied by laser irradiation, the BSA-CuNPs elicited significantly higher cytotoxicity on tumor cells than the control group. Preliminary animal studies to determine the biosafety and pharmacokinetics (PK) profiles exhibited that the BSA-CuNPs have a maximum tolerable dose (MTD) of 16 mgCu/kg and a relatively long plasma half-life of 1.98 h. Overall, our findings demonstrated that BSA-CuNPs might be a potential photothermal therapeutic agent for cancer treatment.

Pharmaceutical Strategies to Improve Druggability of Potential Drug Candidates in Nonalcoholic Fatty Liver Disease Therapy.

Nonalcoholic fatty liver disease (NAFLD) has become globally prevalent and is the leading cause of chronic liver disease. Although NAFLD is reversible without medical intervention in the early stage, the condition could be sequentially worsened to nonalcoholic steatohepatitis (NASH) and, eventually, cirrhosis and hepatic cancer. The progression of NAFLD is related to various factors such as genetics, pre-disposed metabolic disorders, and immunologic factors. Thankfully, to date, there have been accumulating research efforts and, as a result, different classes of potent drug candidates have been discovered. In addition, there have also been various attempts to explore pharmaceutical strategies to improve the druggability of drug candidates. In this review, we provided a brief overview of the drug candidates that have undergone clinical trials. In the latter part, strategies for developing better drugs are discussed.

Mesoporous Silica Nanoparticles as a Potential Nanoplatform: Therapeutic Applications and Considerations.

With advances in nanotechnology, nanoparticles have come to be regarded as carriers of therapeutic agents and have been widely studied to overcome various diseases in the biomedical field. Among these particles, mesoporous silica nanoparticles (MSNs) have been investigated as potential nanocarriers to deliver drug molecules to various target sites in the body. This review introduces the physicochemical properties of MSNs and synthesis procedures of MSN-based nanoplatforms. Moreover, we focus on updating biomedical applications of MSNs as a carrier of therapeutic or diagnostic cargo and review clinical trials using silica-nanoparticle-based systems. Herein, on the one hand, we pay attention to the pharmaceutical advantages of MSNs, including nanometer particle size, high surface area, and porous structures, thus enabling efficient delivery of high drug-loading content. On the other hand, we look through biosafety and toxicity issues associated with MSN-based platforms. Based on many reports so far, MSNs have been widely applied to construct tissue engineering platforms as well as treat various diseases, including cancer, by surface functionalization or incorporation of stimuli-responsive components. However, even with the advantageous aspects that MSNs possess, there are still considerations, such as optimizing physicochemical properties or dosage regimens, regarding use of MSNs in clinics. Progress in synthesis procedures and scale-up production as well as a thorough investigation into the biosafety of MSNs would enable design of innovative and safe MSN-based platforms in biomedical fields.

Paliperidone-Cation Exchange Resin Complexes of Different Particle Sizes for Controlled Release.

This study aimed to develop electrolyte complexes of paliperidone (PPD) with various particle sizes using cation-exchange resins (CERs) to enable controlled release (both immediate and sustained release). CERs of specific particle size ranges were obtained by sieving commercial products. PPD-CER complexes (PCCs) were prepared in an acidic solution of pH 1.2 and demonstrated a high binding efficiency (>99.0%). PCCs were prepared with CERs of various particle sizes (on average, 100, 150, and 400 µm) at the weight ratio of PPD to CER (1:2 and 1:4). Physicochemical characterization studies such as Fourier-transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy between PCCs (1:4) and physical mixtures confirmed PCC formation. In the drug release test, PPD alone experienced a complete drug release from PCC of >85% within 60 min and 120 min in pH 1.2 and pH 6.8 buffer solutions, respectively. Alternatively, PCC (1:4) prepared with CER (150 µm) formed spherical particles and showed an almost negligible release of PPD in pH 1.2 buffer (<10%, 2 h) while controlling the release in pH 6.8 buffer (>75%, 24 h). The release rate of PPD from PCCs was reduced with the increase in CER particle size and CER ratio. The PCCs explored in this study could be a promising technology for controlling the release of PPD in a variety of methods.

Liposomal Iron Oxide Nanoparticles Loaded with Doxorubicin for Combined Chemo-Photothermal Cancer Therapy.

Iron oxide nanoparticle (IONP) possesses unique advantages over other nanoparticles in the use of cancer imaging and therapy. Specifically, it has drawn great attention in the emerging research field of photothermal cancer therapy. Herein, we developed doxorubicin (DOX)-loaded liposomal IONP (Lipo-IONP/DOX) and evaluated in vitro and in vivo their applicability for combined chemo-photothermal cancer therapy. The Lipo-IONP was synthesized by the thin-film evaporation method. The prepared Lipo-IONP was observed as about a 240 nm-sized agglomerate of globular-shaped nanoparticles. The TEM and FT-IR data evidenced the successful formation of liposomal IONP. The superparamagnetic property of the Lipo-IONP was confirmed by the SQUID analysis. The DSC data showed a transition temperature of about 47-48 °C for the mixed lipids composing the Lipo IONP, and the DOX release studies revealed the feasibility of induced burst release of DOX by laser irradiation. The Lipo-IONP/DOX possessed a plasma half-life of 42 min, which could ensure sufficient circulation time for magnetic tumor targeting. The in vivo magnetic targeting enabled a significant increase (6.3-fold) in the tumor accumulation of Lipo-IONP/DOX, leading to greater photothermal effects. Finally, the preliminary efficacy study evidenced the applicability as well as the safety of the Lipo-IONP/DOX for use in combined chemo-photothermal cancer therapy. Overall, the study results demonstrated that the Lipo-IONP/DOX might serve as an effective and safe agent for combined chemo-photothermal cancer therapy.

Preparation and Characterization of Pazopanib Hydrochloride-Loaded Four-Component Self-Nanoemulsifying Drug Delivery Systems Preconcentrate for Enhanced Solubility and Dissolution.

The aim of this study was to develop a four-component self-nanoemulsifying drug delivery system (FCS) to enhance the solubility and dissolution of pazopanib hydrochloride (PZH). In the solubility test, PZH showed a highly pH-dependent solubility (pH 1.2 > water >> pH 4.0 and pH 6.8) and was solubilized at 70 °C in the order Kollisolv PG (5.38%, w/w) > Kolliphor RH40 (0.49%) > Capmul MCM C10 (0.21%) and Capmul MCM C8 (0.19%), selected as the solubilizer, the surfactant, and the oils, respectively. In the characterization of the three-component SNEDDS (TCS) containing Kolliphor RH40/Capmul MCM C10, the particle size of dispersion was very small (<50 nm) and the PZH loading was 0.5% at the weight ratio of 9/1. In the characterization of FCS containing additional Kollisolv PG to TCS, PZH loading was increased to 5.30% without any PZH precipitation, which was 10-fold higher compared to the TCS. The optimized FCS prepared with the selected formulation (Kolliphor RH40/Capmul MCM C10/Kollisolv PG) showed a consistently complete and high dissolution rate (>95% at 120 min) at four different pHs with 1% polysorbate 80, whereas the raw PZH and Kollisolv PG solution showed a pH-dependent poor dissolution rate (about 40% at 120 min), specifically at pH 6.8 with 1% polysorbate 80. In conclusion, PZH-loaded FCS in this work demonstrated enhanced solubility and a consistent dissolution rate regardless of medium pH.

Development of Alectinib-Suspended SNEDDS for Enhanced Solubility and Dissolution.

Alectinib hydrochloride (ALH), a tyrosine kinase inhibitor, is a practically water-insoluble drug classified as BCS class IV. The present study aimed to develop novel suspended self-nanoemulsifying drug delivery system (Su-SNEDDS) to enhance the solubility and dissolution rate. The Su-SNEDDS was prepared by saturation and suspension of ALH in SNEDDS with ultrasonication energy. According to evaluation by the dispersion test and the results of particle size analysis, the selected SNEDDS composed of Kolliphor HS 15 and Capmul MCM C8 as surfactant and oil, respectively, showed a complete dissolution within 30 min. However, the SNEDDS loaded and solubilized only small amount of ALH (<0.6%, w/w). On the other hand, 10% ALH-loaded Su-SNEDDS containing small and micronized ALH particles of <5 µm had about 20-fold higher ALH-loading% than the SNEDDS and reached a 100% dissolution rate within 30 min in 1% sodium lauryl sulfate (SLS) pH 1.2 buffer. In the dispersion test and microscopic observation, micronized ALH particles in the Su-SNEDDS were readily dispersed in the dissolution medium with spontaneous nanoemulsion formation and instantly solubilized with the aid of SLS. Taken together, our results suggest that the Su-SNEDDS would be a potent oral dosage form to enhance the solubilization and dissolution rate of ALH in a new technological way.

Combined Application of Prototype Ultrasound and BSA-Loaded PLGA Particles for Protein Delivery.

PURPOSE: To develop an in vitro culture system for tissue engineering to mimic the in vivo environment and evaluate the applicability of ultrasound and PLGA particle system. METHODS: For tissue engineering, large molecules such as growth factors for cell differentiation should be supplied in a controlled manner into the culture system, and the in vivo microenvironment need to be reproduced in the system for the regulation of cellular function. In this study, portable prototype ultrasound with low intensity was devised and tested for protein release from bovine serum albumin (BSA)-loaded poly(lactic-co-glycolic acid) (PLGA) particles. RESULTS: BSA-loaded PLGA particles were prepared using various types of PLGA reagents and their physicochemical properties were characterized including particle size, shape, or aqueous wetting profiles. The BSA-loaded formulation showed nano-ranged size distribution with optimal physical stability during storage period, and protein release behaviors in a controlled manner. Notably, the application of prototype ultrasound with low intensity influenced protein release patterns in the culture system containing the BSA-loaded PLGA formulation. The results revealed that the portable ultrasound set controlled by the computer could contribute for the protein delivery in the culture medium. CONCLUSIONS: This study suggests that combined application with ultrasound and protein-loaded PLGA encapsulation system could be utilized to improve culture system for tissue engineering or cell regeneration therapy.

In Vitro and In Vivo Evaluation of PEGylated Starch-Coated Iron Oxide Nanoparticles for Enhanced Photothermal Cancer Therapy.

Iron oxide nanoparticles (IONPs) possess versatile utility in cancer theranostics, thus, they have drawn enormous interest in the cancer research field. Herein, we prepared polyethylene glycol (PEG)-conjugated and starch-coated IONPs ("PEG-starch-IONPs"), and assessed their applicability for photothermal treatment (PTT) of cancer. The prepared PEG-starch-IONPs were investigated for their physical properties by transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, and dynamic light scattering (DLS). The pharmacokinetic study results showed a significant extension in the plasma half-life by PEGylation, which led to a markedly increased (5.7-fold) tumor accumulation. When PEG-starch-IONPs were evaluated for their photothermal activity, notably, they displayed marked and reproducible heating effects selectively on the tumor site with laser irradiation. Lastly, efficacy studies demonstrated that PEG-starch-IONPs-based PTT may be a promising mode of cancer therapy.

BSA-Silver Nanoparticles: A Potential Multimodal Therapeutics for Conventional and Photothermal Treatment of Skin Cancer.

Silver nanoparticles (NPs) have attracted a considerable interest in the field of cancer research due to their potential utility in cancer therapy. In the present study, we developed bovine serum albumin (BSA)-coated silver NPs (BSA-Silver NPs) and characterized in vitro multimodal therapeutic activities of NPs for the treatment of skin cancer. BSA-Silver NPs were synthesized by a single-step reduction process, and the successful preparation was verified through a list of physical characterizations, including transmission electron microscopy (TEM), ultraviolet-visible (UV-VIS) light spectroscopy, dynamic light scattering (DLS), and Fourier transform infrared (FT-IR) spectroscopy. The synthesized BSA-Silver NPs showed marked cytocidal effects on B16F10 melanoma cells, which was likely caused by oxidative stress. BSA-Silver NPs also elicited significant anti-angiogenic effects on HUVEC (human umbilical vein endothelial cell) by inhibiting their proliferation, migration, and tube formation. Moreover, BSA-Silver NPs showed a considerable light-to-heat conversion ability, suggesting their utility as photothermal agents. Overall, our findings suggest that BSA-Silver NPs may be promising candidates for the multimodal therapy of skin cancer.

BSA/Silver Nanoparticle-Loaded Hydrogel Film for Local Photothermal Treatment of Skin Cancer.

PURPOSE: To develop a hydrogel film containing bovine serum albumin (BSA)-coated silver nanoparticles (BSA/AgNP) and evaluate its applicability for topical photothermal treatment (PTT) of skin cancer. METHODS: BSA/AgNP-loaded hydrogel films were prepared and their swelling, bioadhesive, mechanical, and photothermal properties were characterized in vitro and in vivo. RESULTS: The synthesized BSA/AgNP exhibited a narrow size distribution with good size stability and, notably, possessed great photothermal activity that could stably maintain through repetitive laser irradiation. The BSA/AgNP-loaded hydrogel films showed favorable swelling, bioadhesive, tensile, and photothermal properties. Based on these results, when tested the anti-cancer effects in B16F10 s.c. tumor-bearing mice, the PTT with the topical treatment of BSA/AgNP-loaded hydrogel films could significantly inhibit the tumor growth by a single treatment with no apparent toxicity. CONCLUSIONS: Overall, the results of this study demonstrated that the BSA/AgNP-loaded hydrogel films may serve as an effective but safe topical PTT agent for the treatment of skin cancer.

Synergistic Effect of Growth Factor Releasing Polymeric Nanoparticles and Ultrasound Stimulation on Osteogenic Differentiation.

Mesenchymal stem cells (MSCs) have been extensively used in the tissue regeneration therapy. Ex vivo therapy with well-differentiated osteogenic cells is known as an efficient treatment for musculoskeletal diseases, including rheumatoid diseases. However, along with its high cost, the current therapy has limitations in terms of restoring bone regeneration procedures. An efficient process for the cell differentiation to obtain a large number of functionalized osteogenic cells is necessary. Therefore, it is strongly recommended to develop strategies to produce sufficient numbers of well-differentiated osteogenic cells from the MSCs. In general, differentiation media with growth factors have been used to facilitate cell differentiation. In the present study, the poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporating the growth factors were included in the media, resulting in releasing growth factors (dexamethasone and ß-glycerophosphate) in the media in the controlled manner. Stable growth and early differentiation of osteogenic cells were achieved by the PLGA-based growth factor releasing system. Moreover, low intensity pulsed ultrasound was applied to this system to induce cell differentiation process. The results revealed that, as a biomarker at early stage of osteogenic cell differentiation, Lamin A/C nuclear protein was efficiently expressed in the cells growing in the presence of PLGA-based growth factor reservoirs and ultrasound. In conclusion, our results showed that the ultrasound stimulation combined with polymeric nanoparticles releasing growth factors could potentially induce osteogenic cell differentiation.

Genetic engineering of novel super long-acting Exendin-4 chimeric protein for effective treatment of metabolic and cognitive complications of obesity.

A common bottleneck challenge for many therapeutic proteins lies in their short plasma half-lives, which often makes the treatment far less compliant or even disables achieving sufficient therapeutic efficacy. To address this problem, we introduce a novel drug delivery strategy based on the genetic fusion of an albumin binding domain (ABD) and an anti-neonatal Fc receptor (FcRn) affibody (AFF) to therapeutic proteins. This ABD-AFF fusion strategy can provide a synergistic effect on extending the plasma residence time by, on one hand, preventing the rapid glomerular filtration via ABD-mediated albumin binding and, on the other hand, increasing the efficiency of FcRn-mediated recycling by AFF-mediated high-affinity binding to the FcRn. In this research, we explored the feasibility of applying the ABD-AFF fusion strategy to exendin-4 (EX), a clinically available anti-diabetic peptide possessing a short plasma half-life. The EX-ABD-AFF produced from the E. coli displayed a remarkably (241-fold) longer plasma half-life than the SUMO tagged-EX (SUMO-EX) (0.7 h) in mice. Furthermore, in high-fat diet (HFD)-fed obese mice model, the EX-ABD-AFF could provide significant hypoglycemic effects for over 12 days, accompanied by a reduction of body weight. In the long-term study, the EX-ABD-AFF could significantly reverse the obesity-related metabolic complications (hyperglycemia, hyperlipidemia, and hepatic steatosis) and, moreover, improve cognitive deficits. Overall, this study demonstrated that the ABD-AFF fusion could be an effective strategy to greatly increase the plasma half-lives of therapeutic proteins and thus markedly improve their druggability.

ICG-Loaded PEGylated BSA-Silver Nanoparticles for Effective Photothermal Cancer Therapy.

PURPOSE: Indocyanine green (ICG), a near infrared (NIR) dye clinically approved in medical diagnostics, possesses great heat conversion efficiency, which renders itself as an effective photosensitizer for photothermal therapy (PTT) of cancer. However, there remain bottleneck challenges for use in PTT, which are the poor photo and plasma stability of ICG. To address these problems, in this research, ICG-loaded silver nanoparticles were prepared and evaluated for the applicability as an effective agent for photothermal cancer therapy. METHODS AND RESULTS: PEGylated bovine serum albumin (BSA)-coated silver core/shell nanoparticles were synthesized with a high loading of ICG ("PEG-BSA-AgNP/ICG"). Physical characterization was carried out using size analyzer, transmission electron microscopy, and Fourier transform infrared spectrophotometry to identify successful preparation and size stability. ICG-loading content and the photothermal conversion efficiency of the particles were confirmed with inductively coupled plasma mass spectrometry and laser instruments. In vitro studies showed that the PEG-BSA-AgNP/ICG could provide great photostability for ICG, and their applicability for PTT was verified from the cellular study results. Furthermore, when the PEG-BSA-AgNP/ICG were tested in vivo, study results exhibited that ICG could stably remain in the blood circulation for a markedly long period (plasma half-life: 112 min), and about 1.7% ID/g tissue could be accumulated in the tumor tissue at 4 h post-injection. Such nanoparticle accumulation in the tumor enabled tumor surface temperature to be risen to 50°C (required for photo-ablation) by laser irradiation and led to successful inhibition of tumor growth in the B16F10 s.c. syngeneic nude mice model, with minimal systemic toxicity. CONCLUSION: Our findings demonstrated that PEG-BSA-AgNPs could serve as effective carriers for delivering ICG to the tumor tissue with great stability and safety.

Development and characterization of a superabsorbing hydrogel film containing Ulmus davidiana var. Japonica root bark and pullulan for skin wound healing.

Ulmus davidiana var. japonica (UD) has widely been used in Korean traditional medicine for the treatment of various types of diseases including inflammation and skin wounds. The UD root bark powders possess gelling activity with an excellent capacity for absorbing water. This distinct property could make the UD root bark powders to be a great material for manufacturing a gel film specifically for the healing of large and highly exudating wounds (e.g., pressure sores and diabetic ulcers). In this research, we separated the UD root bark powder into 4 different samples based on their sizes and then tested their water absorption capacity and flowability. Based on these results, 75-150 µm sized and below 75 µm sized samples of UD root bark powders were chosen, and UD gel films were prepared. The UD gel films showed good thermal stability and mechanically improved properties compared with pullulan only gel film with excellent swelling capacity and favorable skin adhesiveness. Further, in the animal studies with the skin wound mice model, the UD gel films exhibited significant therapeutic effects on accelerating wound closure and dermal regeneration. Overall, this study demonstrated the applicability of UD root bark powders for hydrogel wound dressing materials, and the potential of UD gel films to be superior wound dressings to currently available ones.

Drug Delivery Strategies for Enhancing the Therapeutic Efficacy of Toxin-Derived Anti-Diabetic Peptides.

Toxin peptides derived from the skin secretions of amphibians possess unique hypoglycemic activities. Many of these peptides share cationic and amphipathic structural similarities and appear to possess cell-penetrating abilities. The mechanism of their insulinotropic action is yet not elucidated, but they have shown great potential in regulating the blood glucose levels in animal models. Therefore, they have emerged as potential drug candidates as therapeutics for type 2 diabetes. Despite their anti-diabetic activity, there remain pharmaceutical challenges to be addressed for their clinical applications. Here, we present an overview of recent studies related to the toxin-derived anti-diabetic peptides derived from the skin secretions of amphibians. In the latter part, we introduce the bottleneck challenges for their delivery in vivo and general drug delivery strategies that may be applicable to extend their blood circulation time. We focus our research on the strategies that have been successfully applied to improve the plasma half-life of exendin-4, a clinically available toxin-derived anti-diabetic peptide drug.

Development of 20(S)-Protopanaxadiol-Loaded SNEDDS Preconcentrate Using Comprehensive Phase Diagram for the Enhanced Dissolution and Oral Bioavailability.

In this study, we aimed to develop a 20(S)-protopanaxadiol (PPD)-loaded self-nanoemulsifying drug delivery system (SNEDDS) preconcentrate (PSP) using comprehensive ternary phase diagrams for enhanced solubility, physical stability, dissolution, and bioavailability. Capmul MCM C8 and Capryol 90 were selected as the oil phase owing to the high solubility of PPD in these vehicles (>15%, w/w). Novel comprehensive ternary phase diagrams composed of selected oil, surfactant, and PPD were constructed, and the solubility of PPD and particle size of vehicle was indicated on them for the effective determination of PSP. PSPs were confirmed via particle size distribution, physical stability, and scanning electron microscope (SEM) with the dispersion of water. The optimized PSP (CAPRYOL90/Kolliphor EL/PPD = 54/36/10, weight%) obtained from the six possible comprehensive ternary phase diagrams showed a uniform nanoemulsion with the particle size of 125.07 ± 12.56 nm without any PPD precipitation. The PSP showed a dissolution rate of 94.69 ± 2.51% in 60 min at pH 1.2, whereas raw PPD showed negligible dissolution. In oral pharmacokinetic studies, the PSP group showed significantly higher Cmax and AUCinf values (by 1.94- and 1.81-fold, respectively) than the raw PPD group (p < 0.05). In conclusion, the PSP formulation with outstanding solubilization, dissolution, and in-vivo oral bioavailability could be suggested using effective and comprehensive ternary phase diagrams.