Emulsion Solvent Evaporation Method Research Articles

Development of Hydroxyapatite/Polycaprolactone Composite Biomaterials for Laser Powder Bed Fusion: Evaluation of Powder Characteristics, Mechanical Properties and Biocompatibility.

Hydroxyapatite/polycaprolactone (HA/PCL) composites have been extensively explored in laser powder bed fusion (L-PBF) for bone tissue engineering. However, conventional mechanical mixing methods for preparing composite powders often yield inhomogeneous compositions and suboptimal flowability. In this study, HA/PCL powders were prepared and optimized for L-PBF using the modified emulsion solvent evaporation method. The morphology, flowability and thermal and rheological properties of the powders were systematically investigated, along with the mechanical and biological properties of the fabricated specimens. The HA/PCL powders exhibited spherical morphologies with a homogeneous distribution of HA within the particles. The addition of small amounts of HA (5 wt% and 10 wt%) enhanced the processability and increased the maximum values of the elastic modulus and yield strength of the specimens from 129.8 MPa to 166.2 MPa and 20.2 MPa to 25.1 MPa, respectively, while also improving their biocompatibility. However, excessive addition resulted in compromised sinterability, thereby affecting both mechanical and biological properties.

Pharmacokinetic and Pharmacodynamic Evaluation of Telmisartan-loaded Novel Curcumin-tagged Solid Nanodispersion for the Treatment of Diabetic Nephropathy in an Animal Model

Aim: This study aimed to evaluate the therapeutic efficacy of telmisartan-loaded novel curcumin-tagged solid nanodispersion in streptozotocin-nicotinamide-induced diabetic nephropathy in Wistar rats. Objective: The objective of this study was to perform a comprehensive pharmacokinetic and pharmacodynamic evaluation of a novel curcumin-tagged solid nanodispersion loaded with telmisartan, with the aim of assessing its potential as a treatment for diabetic nephropathy in an animal model. Specifically, the following objectives will be addressed: formulation and character-ization, in vitro evaluation, pharmacokinetics and pharmacodynamics evaluation, and compara-tive analysis. Materials and Methods: Telmisartan-loaded curcumin-tagged solid nanodispersion was prepared using the emulsion solvent evaporation method. The optimized formulation was evaluated for pharmacokinetic and pharmacodynamic parameters in an animal model. Wistar rats were divided into 5 groups, with 6 animals in each group. Diabetes was induced using nicotinamide (240 mg/kg) and streptozotocin (55 mg/kg, i.p.) injections in the animals. After 30 to 45 days of intro-duction, diabetic nephropathy was manifested. The kidneys and pancreas were used for histological analysis and renal and pancreatic damage assessment. Results: In-vivo studies showed better bioavailability with the t1/2 and Cmax of TLS-15 was 14.92 ± 0.47 hours and 0.32 ± 0.009, respectively, within 2 hours as compared to the t1/2 and Cmax of MP was 4.38 ± 0.19 hours and 0.19 ± 0.008 owing to the better dissolution due to solubility improvement. When compared to the commercially available product, TLS-15 was found to have blood glucose and body weight that were, respectively, 1.01 and 1.03 times higher. Kidney measures, such as serum urea and creatinine, were found to be 0.71 and 1.16 times lower for TLS-15, respectively, and albumin had a value that was 1.13 times higher than for the commercial formulation. Urine indicators, urine albumin, and creatinine estimations, as well as cytokine estimations, revealed that TLS-15 had creatinine levels that were 1.17 times higher and IL-6 lev-els that were 0.77 times higher than those of a commercial batch. Conclusion: The findings strongly support the renoprotective and pancreatic protective effects of TLS and Cur (SND-Solid Nanodispersion) combined by lowering levels of cytokines factor (IL-6), kidney, and lipid parameters. The postulated mechanism might be the combined inhibitory action of TLS and Cur.

Synthesis and evaluation of bone targeting PLGA nanoparticles loaded with components of traditional Chinese medicine formulas.

Targeted nanoparticles' preparation can enhance local drug concentration and reduce the side effects of drugs in non-targeted organs. At present, many patents have been applied for in the field of bone-targeted nanoparticles' preparations. They play an important role in the treatment and diagnosis of diseases. In this experiment, nanoparticles with bone targeting function were prepared by poly(lactic-co-glycolic acid) (PLGA) copolymer and tetracycline. These nanoparticles contain active ingredients in the Huangqi Sanxian decoction, a kind of Traditional Chinese Medicine (TCM) compound formula. These nanoparticles are predicted to be useful in the treatment of osteoporosis. Synthesis of tetracycline targeting groups was performed by acylation reaction, and PLGA nanoparticles were prepared by the Emulsification-solvent Evaporation Method. The appearance and particle size of the product were evaluated, and the effects of nanoparticles on the physiological activities of osteoblasts were observed. Finally, the bone-targeting ability of targeted nanoparticles in vivo and in vitro was investigated. The average particle size of the nanoparticles was about 200 nm, and the average drug entrapment was 60%. In vitro evaluation of osteoblasts assay showed that the nanoparticles can be well taken by cells. Their good biocompatibility and sustained-release properties reduce the toxic side effects of drugs when they promote osteoblasts' physiological activities. The results of the in vitro and in vivo bone targeting ability assays showed that tetracycline modified nanoparticles could effectively accumulate in the bone, indicating the great bone-targeting ability of the nanoparticles. The use of PLGA to load active components in the TCM compound formulas and remodel targeting groups is expected to improve drug efficacy, reduce drug dosage, and effects on non- action sites. This may provide new ideas for the development of TCM compound dosage forms. In summary, we prepared PLGA nanoparticles of multiple TCM ingredients with bone targeting ability, and they had good morphological appearance, and a promoting effect on various physiological activities of osteoblasts.

Quality-by-Design Based Development of Doxycycline Hyclate-Loaded Polymeric Microspheres for Prolonged Drug Release.

This study explores a novel approach to address the challenges of delivering highly water-soluble drug molecules by employing hydrophobic ion-pairing (HIP) complexes within poly (lactic-co-glycolic acid) (PLGA) microspheres. The HIP complex, formed between doxycycline hyclate (DH) and docusate sodium (DS), renders the drug hydrophobic. The development of the microspheres was done using the QbD approach, namely, Box-Behnken Design (BBD). A comprehensive characterization of the HIP complex confirmed the successful conversion of DH. DH and the HIP complex were effectively loaded into PLGA microspheres using the oil-in-water (O/W) emulsion solvent evaporation method. Results demonstrated significant improvements in percentage entrapment efficiency (% EE) and drug loading (% DL) for DH within the HIP complex-loaded PLGA microspheres compared to DH-loaded microspheres alone. Additionally, the initial burst release of DH reduced to 3% within the initial 15min, followed by sustained drug release over 8days. The modified HIP complex strategy offers a promising platform for improving the delivery of highly water-soluble small molecules. It provides high % EE, % DL, minimal initial burst release, and sustained release, thus having the potential to enhance patient compliance and drug delivery efficiency.

Polylactic Glycolic Acid-Mediated Delivery of Plectasin Derivative NZ2114 in Staphylococcus epidermidis Biofilms.

Antimicrobial peptides (AMPs) are antibiotic candidates; however, their instability and protease susceptibility limit clinical applications. In this study, the polylactic acid-glycolic acid (PLGA)-polyvinyl alcohol (PVA) drug delivery system was screened by orthogonal design using the double emulsion-solvent evaporation method. NZ2114 nanoparticles (NZ2114-NPs) displayed favorable physicochemical properties with a particle size of 178.11 ± 5.23 nm, polydispersity index (PDI) of 0.108 ± 0.10, ζ potential of 4.78 ± 0.67 mV, actual drug-loading rate of 4.07 ± 0.37%, encapsulation rate of 81.46 ± 7.42% and cumulative release rate of 67.75% (120 h) in PBS. The results showed that PLGA encapsulation increased HaCaT cell viability by 20%, peptide retention in 50% serum by 24.12%, and trypsin tolerance by 4.24-fold. Meanwhile, in vitro antimicrobial assays showed that NZ2114-NPs had high inhibitory activity against Staphylococcus epidermidis (S. epidermidis) (4-8 μg/mL). Colony counting and confocal laser scanning microscopy (CLSM) confirmed that NZ2114-NPs were effective in reducing the biofilm thickness and bacterial population of S. epidermidis G4 with a 99% bactericidal rate of persister bacteria, which was significantly better than that of free NZ2114. In conclusion, the results demonstrated that PLGA nanoparticles can be used as a reliable NZ2114 delivery system for the treatment of biofilm infections caused by S. epidermidis.

Development of novel polymer haemoglobin based particles as an antioxidant, antibacterial and an oxygen carrier agents

This innovative work aims to develop highly biocompatible and degradable nanoparticles by encapsulating haemoglobin (Hb) within poly-ε-caprolactone for novel biomedical applications. We used a modified double emulsion solvent evaporation method to fabricate the particles. A Scanning electron microscope (SEM) characterized them for surface morphology. Fourier Transform Infrared Spectroscopy (FTIR) and Ultraviolet–visible spectroscopies (UV–visible) elucidated preserved chemical and biological structure of encapsulated haemoglobin. The airproof equilibrium apparatus obtained the oxygen-carrying capacity and P50 values. The DPPH assay assessed free radical scavenging potential. The antibacterial properties were observed using four different bacterial strains by disk diffusion method. The MTT assay investigates the cytotoxic effects on mouse fibroblast cultured cell lines (L-929). The MTT assay showed that nanoparticles have no toxicity over large concentrations. The well-preserved structure of Hb within particles, no toxicity, high oxygen affinity, P50 value, and IC50 values open the area of new research, which may be used as artificial oxygen carriers, antioxidant, and antibacterial agents, potential therapeutic agents as well as drug carrier particles to treat the cancerous cells. The novelty of this work is the antioxidant and antibacterial properties of developed nanoparticles are not been reported yet. Results showed that the prepared particles have strong antioxidant and antibacterial potential.

Development and In Vivo Evaluation of Sustained Release Microparticles Loaded with Levothyroxine for Hypothyroidism Treatment

Hypothyroidism is a chronic condition combated by a daily oral supplementation of levothyroxine. In addition to the need for frequent dosing, oral administration may result in variable absorption of the drug leading to a failure in achieving normal thyroid function. Therefore, the development of a long-acting injectable system capable of delivering the drug is necessary. This work was aimed at developing sustained release microparticles loaded with levothyroxine. The microparticles were produced through the emulsification-solvent evaporation method using 2 grades of biocompatible and biodegradable polyesters: poly(ᴅ,ʟ-lactide-co-glycolide) (PLGA) and poly(ᴅ,ʟ-lactide) (PLA). Both polymers produced microparticles with very similar sizes (1.9 µm) and zeta potential values (around -22.0 mV). However, PLA microparticles had a significantly higher drug loading (6.1% vs. 4.4%, respectively) and encapsulation efficiency (36.8%, vs. 26.1%, respectively) when compared to PLGA counterparts. While both types of microparticles displayed a biphasic release pattern in vitro, a slower rate of release was observed with PLA microparticles. Moreover, a similar biphasic release pattern was found in vivo, with an initial phase of rapid release followed by a slower phase in the subsequent 10 days. These results indicate the possibility of developing levothyroxine loaded polyester microparticles as a potential long-acting thyroid hormone replacement therapy.

Development of silibinin-loaded nanostructured lipid carriers for Alzheimer's disease induced by amyloid beta in Wistar rats.

Objective. The purpose of this study is to develop, optimize, and evaluate the in vivo effectiveness of orally administered silibinin-loaded nanostructured lipid carriers (SB-NLCs) in amyloid β-induced Alzheimer's disease in Wistar rats. Methods. The emulsification-solvent evaporation method was used for preparing the NLCs, using stearic acid, triacetin, and Cremophor® RH40. The statistical optimization of SB-NLCs was done using the Box-Behnken design (BBD). Then, the following parameters were evaluated: zeta potential, average size, in vitro drug release, and drug entrapment efficiency. Physicochemical properties of the optimized SB-NLCs were determined by FTIR, DSC, and P-XRD. The behavioral (OFT, NOR, MWM), histological (H&E, Congo Red), and biochemical (TAC, MDA, GSH) tests were conducted on 48 male Wistar rats. Results. The findings showed that the mean particle size, zeta potential and entrapment efficiency of optimized SB-NLCs were 194.71 ± 14.06 nm, -12.46 ± 0.25 mV, and 72.13% ± 1.41, respectively. XRD and DSC studies confirmed a reduction in the crystallinity of SB which occurred due to its embedment in the nanostructured lipid. The FTIR results indicated the lack of existence of any chemical interaction between the carrier components and the drug. Drug release in the external environment was slow and steady. Drug-containing nanoparticles showed good stability during three months of storage at 4 °C. The behavioral test of OFT showed no significant change between groups. The group treated with SB-NLCs showed a markedly higher discrimination rate compared to the Aβ group (p < 0.001). The time of the SB-NLC treated group in the target area was considerably more than the time of the SB and Aβ groups, respectively (p < 0.01, p < 0.001), in the MWM test. Histological and biochemical analysis revealed better results in the SB-NLC group as against the SB group. Conclusion. SB-NLCs can be considered as a promising formulation for the proper treatment of Alzheimer's disease in the oral drug delivery system.

Identification of the Vulnerability of Atherosclerotic Plaques by a Photoacoustic/Ultrasonic Dual-Modal cRGD Nanomolecular Probe.

To explore the feasibility of using cRGD-GNR-PFP-NPs to assess plaque vulnerability in an atherosclerotic plaque mouse model by dual-modal photoacoustic/ultrasonic imaging. A nanomolecular probe containing gold nanorods (GNRs) and perfluoropentane (PFP) coated with the cyclic Arg-Gly-Asp (cRGD) peptide were prepared by double emulsion solvent evaporation and carbodiimide methods. The morphology, particle size, potential, cRGD conjugation and absorption features of the nanomolecular probe were characterized, along with its in vitro phase transformation and photoacoustic/ultrasonic dual-modal imaging properties. In vivo fluorescence imaging was used to determine the distribution of cRGD-GNR-PFP-NPs in vivo in apolipoprotein E-deficient (ApoE-/-) atherosclerotic plaque model mice, the optimal imaging time was determined, and photoacoustic/ultrasonic dual-modal molecular imaging of integrin αvβ3 expressed in atherosclerotic plaques was performed. Pathological assessments verified the imaging results in terms of integrin αvβ3 expression and plaque vulnerability. cRGD-GNR-PFP-NPs were spherical with an appropriate particle size (average of approximately 258.03±6.75 nm), a uniform dispersion, and a potential of approximately -9.36±0.53 mV. The probe had a characteristic absorption peak at 780~790 nm, and the surface conjugation of the cRGD peptide reached 92.79%. cRGD-GNR-PFP-NPs were very stable in the non-excited state but very easily underwent phase transformation under low-intensity focused ultrasound (LIFU) and had excellent photoacoustic/ultrasonic dual-modal imaging capability. Mice fed a high-fat diet for 20 weeks had obvious hyperlipidemia with larger, more vulnerable plaques. These plaques could be specifically targeted by cRGD-GNR-PFP-NPs as determined by in vivo fluorescence imaging, and the enrichment of nanomolecular probe increased with the increasing of plaque vulnerability; the photoacoustic/ultrasound signals of the plaques in the high-fat group were stronger. The pathological assessments were in good agreement with the cRGD-GNR-PFP-NPs plaque accumulation, integrin αvβ3 expression and plaque vulnerability results. A phase variant photoacoustic/ultrasonic dual-modal cRGD nanomolecular probe was successfully prepared and can be used to identify plaque vulnerability safely and effectively.

Nanoparticle‐based sustained drug delivery for the treatment of ocular neovascular diseases

Aims/Purpose: Nanoparticles have shown great potential as a drug delivery system for the treatment of neovascular ocular diseases characterized by the growth of abnormal blood vessels in the retina. The current standard of therapy for neovascular ocular diseases involves administering monoclonal antibody‐based anti‐VEGF drugs via intravitreal injections on a periodic basis. The short half‐lives of these drugs necessitate frequent injections, which can limit the effectiveness of the treatments. Hence, there is a need to develop new approaches for enhanced bioavailability and sustained and long‐lasting delivery of anti‐VEGF drugs. The aim of this study was to utilize poly (glycerol sebacate) (PGS) nanoparticles to achieve an extended release of anti‐VEGF (anti‐vascular endothelial growth factor) drugs, with the objective of reducing the frequency of intravitreal injections required for treatment.Methods: Double emulsion solvent evaporation method was utilized for the synthesis of PGS nanoparticles. Nanoparticle size and polydispersity index (PDI) were determined with dynamic light scattering method.Results: Nanoparticles were synthesized with a size of approximately 150 nm and PDI less than 0.3. The encapsulation efficiency of nanoparticles loaded with anti‐VEGF drugs was found to be 74%. The 30% drug release from nanoparticles in the first 2 months indicates that nanoparticles are a promising candidate for sustained drug release applications. Cell‐viability studies showed that anti‐VEGF drug‐loaded nanoparticles did not exhibit toxicity to ARPE‐19 cells, but they did exhibit anti‐angiogenesis properties by inhibiting the growth of HUVEC cells in a concentration‐dependent manner.Conclusions: The development of new‐generation materials for the storage and preservation of anti‐VEGF drugs, as well as their enhancement with prolonged release, will considerably improve the efficacy of long‐term treatment strategies for ocular neovascular diseases.

Ketoconazole-loading strategy to improve antifungal activity and overcome cytotoxicity on human renal proximal tubular epithelial cells

Ketoconazole (KTZ), an antifungal agent used to treat localized or systemic fungal infections by inhibiting ergosterol synthesis, exhibits restricted efficacy within eukaryotic cells owing to its elevated toxicity and limited solubility in water. This study aims to improve the biological activity and overcome cytotoxic effects in the renal system of the hydrophobic KTZ by incorporating it into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) utilizing biomaterial nano-engineering techniques. KTZ-loaded PLGA NPs (KTZ-NPs) were prepared by single emulsion solvent evaporation method and characterized by using dynamic light scattering (DLS), electrophoretic light scattering (ELS), Fourier transform-infrared (FT-IR) spectroscopy and scanning light microscopy (SEM). Particle size and zeta potential of KTZ-NPs were determined as 182.0 ± 3.27 nm and −27.4 ± 0.56 mV, respectively. Antifungal activity was analyzed with the time-kill and top agar dilution methods on Candida albicans (C. albicans) and Aspergillus flavus (A. flavus). Both KTZ and KTZ-NPs caused a significant decrease in A. flavus cell growth; however, the same effect was only observed in time-killing analysis on C. albicans, indicating a methodological difference in the antifungal analysis. According to the top agar method, the MIC value of KTZ-NPs against A. flavus was 9.1 μg ml−1, while the minimum inhibition concentration (MIC) value of KTZ was 18.2 μg ml−1. The twofold increased antifungal activity indicates that nanoparticular drug delivery systems enhance the water solubility of hydrophobic drugs. In addition, KTZ-NPs were not cytotoxic on human renal proximal tubular epithelial cells (HRPTEpCs) at fungistatic concentration, thus reducing fungal colonization without cytotoxic on renal excretion system cells.

RGD-modified solid lipid nanoparticles improve oral doxorubicin absorption: In vitro and in vivo study

ObjectiveDoxorubicin (DOX), an effective antitumor drug, is widely used in cancer treatment. However, DOX has low oral bioavailability. Owing to its ability to specifically bind the β1 receptor on the surface of M cells, promote the phagocytosis of drugs by M cells, and improve the oral efficacy of drugs, arginine-glycine-aspartic peptide (RGD) is used to modify the oral nanodrug delivery system. MethodsAn emulsion solvent evaporation method was used to prepare DOX-loaded solid lipid nanoparticles (DOX-SLNs), which were further modified with RGD (RGD-DOX-SLNs) by noncovalent interactions. The physicochemical properties, dissolution rate, and cytotoxicity of the SLNs were investigated. An in vitro transparency experiment was performed using the follicle-associated epithelium (FAE) model. In addition, oral bioavailability and gastrointestinal (GI) mucosal irritation were evaluated in rats. ResultsThe cumulative release percentage of DOX at pH 1.2 decreased significantly when DOX was incorporated into the SLNs, which may be dependent on drug diffusion and matrix erosion mechanisms. The cell toxicity was low in Caco-2 cells. No GI mucosal irritation was found in rats. The cellular uptake of RGD-DOX-SLNs in the FAE model was higher than in Caco-2 model. Compared with the DOX group, the area under the plasma concentration-time curve (AUC) of DOX in the RGD-DOX-SLNs group increased 2.25-fold after oral administration to rats. ConclusionsRGD-DOX-SLNs improved DOX transport in the FAE model and enhanced the oral bioavailability of DOX in rats.

Hypoxia-Responsive Golgi-Targeted Prodrug Assembled with Anthracycline for Improved Antitumor and Antimetastasis Efficacy.

Tumor metastasis is an intricate multistep process regulated via various proteins and enzymes modified and secreted by swollen Golgi apparatus in tumor cells. Thus, Golgi complex is considered as an important target for the remedy of metastasis. Currently, Golgi targeting technologies are mostly employed in Golgi-specific fluorescent probes for diagnosis, but their applications in therapy are rarely reported. Herein, we proposed a prodrug (INR) that can target and destroy the Golgi apparatus, which consisted of indomethacin (IMC) as the Golgi targeting moiety and retinoic acid (RA), a Golgi disrupting agent. The linker between IMC and RA was designed as a hypoxia-responsive nitroaromatic structure, which ensured the release of the prototype drugs in the hypoxic tumor microenvironment. Furthermore, INR could be assembled with pirarubicin (THP), an anthracycline, to form a carrier-free nanoparticle (NP) by emulsion-solvent evaporation method. A small amount of mPEG2000-DSPE was added to shield the positive charges and improve the stability of the nanoparticle to obtain PEG-modified nanoparticle (PNP). It was proved that INR released the prototype drugs in tumor cells and hypoxia promoted the release. The Golgi destructive effect of RA in INR was amplified owing to the Golgi targeting ability of IMC, and IMC also inhibited the protumor COX-2/PGE2 signaling. Finally, PNP exhibited excellent curative efficacy on 4T1 primary tumor and its pulmonary and hepatic metastasis. The small molecular therapeutic prodrug targeting Golgi apparatus could be adapted to multifarious drug delivery systems and disease models, which expanded the application of Golgi targeting tactics in disease treatment.

Enhancing Ocular Drug Delivery: The Effect of Physicochemical Properties of Nanoparticles on the Mechanism of Their Uptake by Human Cornea Epithelial Cells.

This study investigates the effect of nanoparticle size and surface chemistry on interactions of the nanoparticles with human cornea epithelial cells (HCECs). Poly(lactic-co-glycolic) acid (PLGA) nanoparticles were synthesized using the emulsion-solvent evaporation method and surface modified with mucoadhesive (alginate [ALG] and chitosan [CHS]) and mucopenetrative (polyethylene glycol [PEG]) polymers. Particles were found to be monodisperse (polydispersity index (PDI) below 0.2), spherical, and with size and zeta potential ranging from 100 to 250 nm and from -25 to +15 mV, respectively. Evaluation of cytotoxicity with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay indicated that incubating cells with nanoparticles for 24 h at concentrations up to 100 μg/mL caused only mild toxicity (70-100% cell viability). Cellular uptake studies were conducted using an in vitro model developed with a monolayer of HCECs integrated with simulated mucosal solution. Evaluation of nanoparticle uptake revealed that energy-dependent endocytosis is the primary uptake mechanism. Among the different nanoparticles studied, 100 nm PLGA NPs and PEG-PLGA-150 NPs showed the highest levels of uptake by HCECs. Additionally, uptake studies in the presence of various inhibitors suggested that macropinocytosis and caveolae-mediated endocytosis are the dominant pathways. While clathrin-mediated endocytosis was found to also be partially responsible for nanoparticle uptake, phagocytosis did not play a role within the studied ranges of size and surface chemistries. These important findings could lead to improved nanoparticle-based formulations that could improve therapies for ocular diseases.

Preparation, Characterization and in vitro/vivo Evaluation of Long-Acting Rivaroxaban-Loaded Microspheres.

Rivaroxaban is widely used for long-term prevention and maintenance therapy of thromboembolic disorders. The existing oral dosage forms of rivaroxaban lead to poor patient adherence because of repeated daily administration. The aim of this study is to design long-acting rivaroxaban- loaded microspheres to reduce dosing frequency and improve patient compliance. Rivaroxaban-loaded microspheres were prepared using the emulsion-solvent evaporation method. The microspheres were evaluated in terms of morphology, particle size, drug loading and encapsulation efficiency, the physical state of the drug in the matrix, in vitro release/release mechanism, and in vivo pharmacokinetics in Sprague Dawley rats. Rivaroxaban-loaded microspheres presented spherical-shaped particles displaying a mean particle size of 89.3 μm, drug loading of 16.5% and encapsulation efficiency of 97.8%. The X-ray diffraction indicated that rivaroxaban existed in crystal form in the microspheres. in vitro release lasting approximately 50 days was characterized as a tri-phasic pattern: (1) an initial burst release, mainly due to the dissolution of drug particles with direct access to the microparticles' surface, (2) a "plateau" phase with a slow-release rate controlled by the diffusion and (3) a final, rapid drug release phase controlled by polymer erosion. Pharmacokinetic studies showed that rivaroxaban microspheres maintained a sustained release for more than 42 days. Rivaroxaban-loaded microspheres have great potential clinical advantages in reducing dosing frequency and improving patient compliance. The data obtained from this study could be used as scientific evidence for decision-making in future formulation development.

Preparation, Characterization, and Release Profile Study of Vincristine Sulfate-loaded Polycaprolactone Nanoparticles

Background: Vincristine sulfate is commonly used to treat different types of cancers. However, its effectiveness is hindered by undesirable side effects, which significantly limit its applications in medicine. Objective: This study aims to prepare vincristine nanoparticles, in order to develop a promising approach for cancer therapy. Methods: Vincristine nanoparticles were prepared by utilizing polycaprolactone as a carrier through the double emulsion method. The morphological characteristics and particle size of the vincristine nanoparticles were examined. The surface charge and average dynamic size, encapsulation efficiency in addition to release profile study were also evaluated. Results: Dynamic Light Scattering confirmed the small size of nanoparticles (~200 nm). SEM showed spherical-shaped nanoparticles with smooth surfaces, and the polydispersity index values of the prepared nanoparticles were below 0.5 in all preparations. The zeta potential of the nanoparticles was found to be negative, which can be attributed to the presence of carboxylic groups in the PCL polymer, The encapsulation efficiency of Vincristine-loaded nanoparticles (NPs) varied from 36% to 57% for all the prepared NPs with varying amounts of PCL. The release profile demonstrated a prolonged release of Vincristine from the nanoparticles compared to the Vincristine solution. Conclusion: The double emulsion solvent evaporation method was used successfully to prepare vincristine- loaded PCL nanoparticles, which suggests that nanoscale carriers hold promise as effective vehicles for delivering chemotherapeutic agents in the treatment of cancer.

Aqueous remote loading of model cationic peptides in uncapped poly(lactide-co-glycolide) microspheres for long-term controlled release.

Remote loading microencapsulation of peptides into polymer microspheres without organic solvent represents a promising alternative to develop long-acting release depots relative to conventional encapsulation methods. Here, we formulated drug-free microspheres from two kinds of uncapped poly(lactide-co-glycolides) (PLGAs), i.e., ring-opening polymerized Expansorb® DLG 50-2A (50/50, 11.2kDa) and Expansorb® DLG 75-2A (75/25, 9.0kDa), and evaluated their potential capacity to remote-load and control the release of two model peptides, leuprolide and octreotide. Degradation and erosion kinetics, release mechanism, and storage stability was also assessed. As control formulations, peptide was loaded in the same PLGA 75/25 polymer by the conventional double emulsion-solvent evaporation method (W/O/W) and remote loaded in polycondensation poly(lactic-co-glycolic acid) 75/25 (Wako 7515, 14.3kDa). Loading content of 6.7%-8.9% w/w (~ 67%-89% encapsulation efficiency (EE)) was attained for octreotide, and that of 9.5% w/w loading (~ 95% EE) was observed for leuprolide, by the remote loading paradigm. Octreotide and leuprolide were both slowly and continuously released in vitro from the remote-loaded Expansorb® DLG 75-2A MPs for over 56days, which was highly similar to that observed from traditionally-loaded formulations by W/O/W (8.8% loading, 52.8% EE). The faster release kinetics was observed for the faster degrading PLGA 50/50 remote-loaded Expansorb® DLG 50-2A MPs relative to microspheres from the PLGA 75/25 Expansorb® DLG 75-2A. Despite slight differences in degradation kinetics, the release mechanism of octreotide from the Expansorb® microspheres, whether remote loaded or by W/O/W, was identical as determined by release vs. mass loss curves. Octreotide acylation was also minimal (< ~ 10%) for this polymer. Finally, drug-free Expansorb® DLG 75-2A MPs displayed excellent storage stability over 3months. Overall, this work offers support for the use of ring-opening Expansorb® PLGA-based microspheres to remote load peptides to create simple and effective long-acting release depots.

Novel Nanoprobe with Combined Ultrasonography/Chemical Exchange Saturation Transfer Magnetic Resonance Imaging for Precise Diagnosis of Tumors.

Given that cancer mortality is usually due to a late diagnosis, early detection is crucial to improve the patient's results and prevent cancer-related death. Imaging technology based on novel nanomaterials has attracted much attention for early-stage cancer diagnosis. In this study, a new block copolymer, poly(ethylene glycol)-poly(l-lactide) diblock copolymer (PEG-PLLA), was synthesized by the ring-opening polymerization method and thoroughly characterized using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance spectroscopy (H-NMR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA). The obtained PEG-PLLA was used to prepare nanoparticles encapsulated with perfluoropentane and salicylic acid by the emulsion-solvent evaporation method, resulting in a new dual-mode nano-image probe (PEG-PLLA@SA·PFP). The zeta potential and mean diameter of the obtained nanoparticles were measured using dynamic light scattering (DLS) with a Malvern Zetersizer Nano. The in vitro biocompatibility of the PEG-PLLA nanoparticles was evaluated with cell migration, hemolysis, and cytotoxicity assays. Ultrasonic imaging was performed using an ultrasonic imaging apparatus, and chemical exchange saturation transfer (CEST) MRI was conducted on a 7.0 T animal scanner. The results of IR and NMR confirmed that the PEG-PLLA was successfully synthesized. The particle size and negative charge of the nanoparticles were 223.8 ± 2.5 nm and -39.6 ± 1.9 mV, respectively. The polydispersity of the diameter was 0.153 ± 0.020. These nanoparticles possessed good stability at 4 °C for about one month. The results of cytotoxicity, cell migration, and hemolysis assays showed that the carrier material was biocompatible. Finally, PEG-PLLA nanoparticles were able to significantly enhance the imaging effect of tumors by the irradiation of ultrasound and saturation by a radiofrequency pulse, respectively. In conclusion, these nanoparticles exhibit promising dual-mode capabilities for US/CEST MR imaging.

Microfluidic-assisted preparation of PLGA nanoparticles loaded with insulin: a comparison with double emulsion solvent evaporation method

Poly lactic-co-glycolic acid (PLGA) is an ideal polymer for the delivery of small and macromolecule drugs. Conventional preparation methods of PLGA nanoparticles (NPs) result in poor control over NPs properties. In this research, a microfluidic mixer was designed to produce insulin-loaded PLGA NPs with tuned properties. Importantly; aggregation of the NPs through the mixer was diminished due to the coaxial mixing of the precursors. The micromixer allowed for the production of NPs with small size and narrow size distribution compared to the double emulsion solvent evaporation (DESE) method. Furthermore, encapsulation efficiency and loading capacity indicated a significant increase in optimized NPs produced through the microfluidic method in comparison to DESE method. NPs prepared by the microfluidic method were able to achieve a more reduction of trans-epithelial electrical resistance values in the Caco-2 cells compared to those developed by the DESE technique that leads to greater paracellular permeation. Compatibility and interaction between components were evaluated by differential scanning calorimetry and fourier transform infrared analysis. Also, the effect of NPs on cell toxicity was investigated using MTT test. Numerical simulations were conducted to analyze the effect of mixing patterns on the properties of the NPs. It was revealed that by decreasing flow rate ratio, i.e. flow rate of the organic phase to the flow rate of the aqueous phase, mixing of the two streams increases. As an alternative to the DESE method, high flexibility in modulating hydrodynamic conditions of the microfluidic mixer allowed for nanoassembly of NPs with superior insulin encapsulation at smaller particle sizes.

Formulation Development and Evaluation of Floating Microspheres of Curcumin

Purpose – There are several approaches that have been developed in order to increase the gastric residence time (GRT) floating drug delivery system is one of them. Floating microspheres improve the bioavailability and releasing for long period of time. In the current investigation curcumin floating microspheres are being developed to extend the drug release. Method - Emulsion solvent evaporation approach is used for development of floating microspheres by using Eudragit RS100, HPMC K100, Ethyl Cellulose as polymers. Acetone and Ethanol was used as a solvent in a ratio of 10:5. Stirring speed of mechanical stirrer was 900rpm. Result - There was no reaction between the drug and excipients according to FTIR analysis. The developed microspheres have virtually spherical shapes and particle size range was between 200 - 420µm. The effectiveness of the drug entrapment was found between 60 - 98.4%. It was found that the buoyancy was between 70 - 92%. The in-vitro drug release was found to be 99.5 of batch 15. The developed microspheres indicated prolonged drug release of 12hrs. The optimized batch was B15. Conclusion - According to results of the research, developing gastro-retentive floating microspheres of curcumin using the emulsion solvent evaporation method with HPMC K100, Eudragit RS100, and ethyl cellulose is a promising method.