Emulsion Solvent Evaporation Technique Research Articles

Preparation and Characterization of Injectable Augmentation Gels Containing Polycaprolactone and Hyaluronic Acid.

Injectable augmentation gels are widely used in the treatment of soft tissue. The composition of these gels has to be continuously improved due to the limitations of the currently available formulations. This study focuses on the development of an innovative injectable gel designed to address current trends and specific needs within the field. The current study utilized a safer hyaluronic acid (HA) gel carrier, created with a less toxic cross-linker, in combination with polycaprolactone (PCL) microspheres at various concentrations. PCL microspheres were prepared using an emulsification-solvent evaporation technique. Six different gel formulations were developed using PCL microspheres and biphasic HA gel structures. The produced microspheres had non-agglomerated, smooth surfaces with an average particle size of approximately 45 ± 0.14 μm. The rheological results of the PCL-HA6 such as storage modulus (G', Pa), loss modulus (G", Pa), complex viscosity (η*), and phase angle (°) at 1 Hz frequency were measured as 553.97 ± 32.48, 368.4 ± 12.24, 105.9 ± 5.27, and 33.65 ± 0.92, respectively, and the injection force was measured as 9.64 ± 1.46. Invitro tests revealed that the PCL-HA6 group showed the highest cell viability compared to the other groups and provided a relative increase in collagen production over time, as demonstrated by the relevant gene expression. The developed PCL/HA gel exhibited biocompatibility and non-toxicity, making it a safe option for soft tissue augmentation. It demonstrated potential for medical applications and exhibited favorable rheological characteristics and injectability.

Mesalamine loaded ethyl cellulose nanoparticles: optimization and in vivo evaluation of antioxidant potential in ulcerative colitis

This study aimed to optimize mesalamine (MES)-nanoparticles (NPs) using Box Behnken Design and investigate itsin vivoantioxidant potential in colon drug targeting. The formulation was prepared using oil/water (O/W) emulsion solvent evaporation technique for time dependent colonic delivery. The optimal formulation with the following parameters composition was selected: polymer concentration (% w/w) (A) = 0.63, surfactant concentration (% w/w) (B) = 0.71, sonication duration (min) (C) = 6. The outcomes showed that ethyl cellulose (EC) NP containing MES has particles size of 142 ± 2.8 nm, zeta potential (ZP) of -24.8 ± 2.3 mV, % EE of 87.9 ± 1.6%, and PDI of 0.226 ± 0.15. Scanning electron microscopy revealed NPs has a uniform and spherical shape. Thein-vitrorelease data disclosed that the EC NPs containing MES showed bursts release of 52% ± 1.6% in simulated stomach media within 2 h, followed by a steady release of 93% ± 2.9% in simulated intestinal fluid that lasted for 48 h. The MES release from NP best match with the Korsmeyer-Peppas model (R2= 0.962) and it followed Fickian diffusion case I release mechanism. The formulation stability over six-months at 25 °C ± 2 °C with 65% ± 5% relative humidity, and 40 °C ± 2 °C with 75% ± 5% relative humidity showed no significant changes in colour, EE, particle sizes and ZP. As perin vivoresults, MES-NP effectively increased glutathione, SOD level and reduces the LPO level as compared to other treatment groups. The findings hold promise that the developed formulation can suitably give in ulcerative colitis.

Smart Coating of Carbon Steel Using Polystyrene Clay Nanocomposites Loaded with Cerium and Silanol Inhibitors: Characterization and Electrochemical Study.

Local Khulays clay was modified to prepare polystyrene clay nanocomposite (PCN) coatings on carbon steel. The PCN coatings were added to microcapsules (MCs) loaded with the corrosion inhibitor PCN(MC). The microcapsules were prepared by the encapsulation of rare-earth metal Ce+3 ions and isobutyl silanol into polystyrene via the double emulsion solvent evaporation (DESE) technique. From characterization techniques, Fourier-transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) with EDX. SEM and FT-IR confirmed the success of the preparation of the PCN(MC). Nanoindentation tests were performed on the thin-film samples. A significant reduction in both the hardness and the reduced modulus was observed for the PCN film compared to the PS film. Electrochemical impedance spectroscopy (EIS) and electrochemical frequency modulation (EFM) all showed an enhanced protection efficiency (%PE) of 3% PCN(MC) over 3% PCN at high temperatures and at different times. The smart coatings were proven by applying the thermal and the mechanical triggers for the 3% PCN(MC) coating. The mechanism of the release of inhibitors was discussed. The self-healing properties of 3% PCN(MC) were evaluated. The enhanced properties of the developed PCN(MC) coatings make them attractive for potential applications in the oil and other industries.

Basil seed mucilage as a bioadhesive polymer: Development of naproxen sodium microspheres and suppositories with in-vitro and ex-vivo studies

Background and purpose: The study explores basil seed mucilage as a bioadhesive carrier for naproxen sodium, demonstrating its ability to enhance solubility when administered rectally. The mucilage, derived from Ocimum basilicum seeds, showed bioadhesive properties and thermal stability, as confirmed by FTIR spectroscopy and X-ray diffraction analysis. Experimental approach: Microspheres were prepared using a double emulsion solvent evaporation technique, varying polymer ratios to optimize drug delivery. Key results: Particle size analysis revealed a range of 456±0.51 to 712±0.21 µm, with larger microspheres formed at higher mucilage concentrations due to increased viscosity. Encapsulation efficiency ranged from 45.01±0.25 % to 79.4±0.93 %, improving with higher basil/alginate ratios. The superior batch, OBM5, showed excellent mucoadhesive qualities in ex-vivo assays, attributed to the increased polymer content, facilitating interaction with rectal mucosa. SEM analysis of OBM5 indicated a spherical, monolithic structure conducive to free flow. Drug release was efficient, with OBM5 achieving 88.7±1.3 % after 7 hours, indicating a control­led release profile. Conclusion: Incorporated into polyethylene glycol (PEG) 4000 suppositories, suppose­tories were completely disintegrated in buffer solution within 25 minutes. The bioadhesive force of basil seed mucilage on rectal mucosa was significantly enhanced, reaching 6.44±0.58 g, correlating with mucilage concentration. These findings underscore the efficacy of basil seed mucilage as a bioadhesive biopolymer for rectal drug delivery systems.

Nanospheres as the delivery vehicle: novel application of Toxoplasma gondii ribosomal protein S2 in PLGA and chitosan nanospheres against acute toxoplasmosis.

Toxoplasma gondii (T. gondii) is a zoonotic disease that poses great harm to humans and animals. So far, no effective T. gondii vaccine has been developed to provide fully protection against such parasites. Recently, numerous researches have focused on the use of poly-lactic-co-glycolic acid (PLGA) and chitosan (CS) for the vaccines against T. gondii infections. In this study, we employed PLGA and CS as the vehicles for T. gondii ribosome protein (TgRPS2) delivery. TgRPS2-PLGA and TgRPS2-CS nanospheres were synthesized by double emulsion solvent evaporation and ionic gelation technique as the nano vaccines. Before immunization in animals, the release efficacy and toxicity of the synthesized nanospheres were evaluated in vitro. Then, ICR mice were immunized intramuscularly, and immune protections of the synthesized nanospheres were assessed. The results showed that TgRPS2-PLGA and TgRPS2-CS nanospheres could induce higher levels of IgG and cytokines, activate dendritic cells, and promote the expression of histocompatibility complexes. The splenic lymphocyte proliferation and the enhancement in the proportion of CD4+ and CD8+ T lymphocytes were also observed in immunized animals. In addition, two types of nanospheres could significantly inhabit the replications of T. gondii in cardiac muscles and spleen tissues. All these obtained results in this study demonstrated that the TgRPS2 protein delivered by PLGA or CS nanospheres provided satisfactory immunoprotective effects in resisting T. gondii, and such formulations illustrated potential as prospective preventive agents for toxoplasmosis.

Design, Devlopment and Evaluation of Gastroretentive Floating Microspheres of Glibenclamide: In-vitro In-vivo Studies .

The current research study was designed to characterize the ethyl cellulose act as a carrier mediator used to prepare a floating microsphere of glibenclamide for developed gastroretentive sustain release floating drug delivery. Different microspheres of glibenclamide were formulated by the emulsion solvent evaporation technique of glibenclamide with EC in different ratios by using two solvent systems (ethanol and chloroform). After evaluating the micropolitics properties, %of yield value, drug loading efficiency, entrapment efficiency, diameter and surface morphology of the microsphere by using DLS and SEM, in-vitro drug release in gastric content, in-vitro buoyancy, and in-vivo floatation using animal model, compatibility study by FTIR, DSC and any other analytical study to demonstrate all formulation (especially GM2) was showing excellent results. So this work shows great gastro etentive floating drug delivery system for prolonged periods of time which is very useful in future for further study.

Two-step emulsification for the fabrication of homogeneous PCL microspheres encapsulating geniposidic acid with antioxidant properties

The mortality rate of neurological disorders is increasing globally, and natural antioxidant geniposidic acid (GPA) holds great potential in the treatment of neuronal oxidative damage. Nevertheless, its inherent instability constrains its pragmatic utilization. Herein, we introduced a drug delivery system capable of protecting unstable natural active compounds from degradation. Among the various methods for preparing drug-loaded microspheres, the emulsification-solvent evaporation technique is one of the most commonly employed due to its efficiency and simplicity. Nevertheless, this method results in microspheres with heterogeneous particle sizes. To address this limitation, we developed a two-step emulsification method involving stirring and homogenization. Using the biocompatible, synthetic, biodegradable polymer polycaprolactone (PCL) as the drug delivery carrier, we prepared GPA-loaded PCL microspheres via the two-step emulsification method. The results demonstrated that the microspheres possessed uniform particle size (polydispersity index = 0.12), excellent drug loading capacity (∼4.86%), sustained drug release profiles (∼68.55% in 264 h), and biocompatibility (cell viability >85%). The in vitro tests showed that the microspheres exerted antioxidant effects by scavenging reactive oxygen species (ROS) induced by oxidative stress, thereby protecting neuronal cells from oxidative damage. This work presents a promising new approach for the treatment of neuronal oxidative damage.

Dexamethasone-loaded PLGA porous microspheres used as 3D-bioprinted bioink promote tissue-engineered cartilage regeneration

The current investigation focused on fabricating and thoroughly analyzing porous microspheres (MPs) comprising poly (lactic-co-glycolic acid, PLGA) encapsulating dexamethasone, by utilizing the water-in-oil-in-water (W/O/W) emulsion solvent evaporation technique. The meticulous characterization encompassed various parameters, including particle size distribution, morphology, and polymer integrity, all of which exhibited consistent attributes across the MPs populations. The analysis of drug content and release kinetics revealed a sustained and controlled liberation of dexamethasone, characterized by an initial burst release within the initial 3 days followed by a gradual, protracted release profile. Subsequent in vivo assessments further validated the potent anti-inflammatory effects of the dexamethasone-loaded PLGA MPs, as evidenced by notable reductions in CD86 immunohistochemical staining intensity, along with the change in membrane thickness. Additionally, the MPs demonstrated an impressive capability to support the maintenance of cartilage phenotype, as indicated by the augmented secretion of cartilage matrix components and elevated glycosaminoglycan content.  

Targeted polymeric primaquine nanoparticles: optimization, evaluation, and in-vivo liver uptake for improved malaria treatment

Primaquine (PQ) is a widely used antimalarial drug, but its high dosage requirements can lead to significant tissue damage and adverse gastrointestinal and hematological effects. Recent studies have shown that nanoformulations can enhance the bioavailability of pharmaceuticals, thereby increasing efficacy, reducing dosing frequency, and minimizing toxicity. In this study, PQ-loaded PLGA nanoparticles (PQ-NPs) were prepared using a modified double emulsion solvent evaporation technique (w/o/w). The PQ-NPs exhibited a mean particle size of 228 ± 2.6 nm, a zeta potential of +27.4 mV, and an encapsulation efficiency of 81.3 ± 3.5%. Scanning electron microscopy (SEM) confirmed their spherical morphology, and the in vitro release profile demonstrated continuous drug release over 72 h. Differential scanning calorimetry (DSC) thermograms indicated that the drug was present in the nanoparticles, with improved physical stability. Fourier-transform infrared spectroscopy (FTIR) analysis showed no interactions between the various substances in the NPs. In vivo studies in Swiss albino mice infected with Plasmodium berghei revealed that the nanoformulated PQ was 20% more effective than the standard oral dose. Biodistribution studies indicated that 80% of the NPs accumulated in the liver, highlighting their potential for targeted drug delivery. This research demonstrates the successful development of a nanomedicine delivery system for antimalarial drugs, offering a promising strategy to enhance treatment efficacy while reducing adverse effects.

IN VITRO EVALUATION OF THE ANTIBACTERIAL EFFECT OF CHITOSAN COATED TEICOPLANIN-LOADED LIPID NANOPARTICLES AGAINST STAPHYLOCOCCUS AUREUS

Objective: The aim of this research is to formulate teicoplanin-loaded solid lipid nanoparticles (SLN) coated with chitosan to sustain teicoplanin release for effective antibacterial therapy. Material and Method: “Double emulsion-solvent evaporation technique was used for the production of SLNs. The nanoparticles were characterised in terms of morphology, size, encapsulation efficacy, in-vitro drug release and antibacterial activity studies after optimization of process and formulation parameters. Result and Discussion: Transmission electron microscopy images confirmed the formation of spherical SLNs. With chitosan coating, the size increased (from 80 nm to 106 nm) and the negative value of zeta potential (- 11.29) changed to positive (+34.41). The in-vitro release data showed prolonged release of teicoplanin from optimized SLN and chitosan-coated SLN (c-SLN) formulations over 1 week. The antibacterial activity study (S. aureus and Methicillin-resistant S. aureus) showed the activity of the teicoplanin loaded SLN formulations. In conclusion, this study demonstrated the potential of c-SLN for effective delivery of teicoplanin.

Phthalocyanine J-aggregate nanoparticles with enormous-redshifted and intense absorption: Potential structure-J-aggregation relationships and application in tumor-associated macrophages-targeted phototheranostics

Phthalocyanines (Pcs) are considered promising in cancer phototherapy. However, their maximum absorption wavelengths are only around 700 nm, which cannot allow deep tissue penetration and leads to poor therapeutic efficacy. To expand their clinical application, significantly shifting their absorption to longer wavelengths is urgently required. Dye J-aggregates exhibit a redshifted absorption relative to its monomer. However, Pc J-aggregates with enormous-redshifted and intense absorption is rarely reported, and little is known about the relationships between Pc structure and J-aggregation. Herein, such Pc J-aggregates are ingeniously conceived. With a yeast β-D-glucan-ursodeoxycholic acid conjugate as a potential tumor-associated macrophages (TAMs)-targeting carrier and 1-(4-carboxyethylphenoxy) zinc (II) phthalocyanine (Pc1) as a model, Pc1 J-aggregate nanoparticle (NanoPc1) is obtained via ultrasonication-aided emulsification-solvent evaporation technique. NanoPc1 displays strong absorption at 830 nm, with a 156 nm redshift. Further investigation on another twenty-four Pcs demonstrates that unsubstituted zinc (II) or magnesium (II) Pc and hydrophobic mono-substituted zinc (II) or magnesium (II) Pcs with mono-substituted phenoxy or phenylthio or naphthoxy as a substituent can readily form desired Pc J-aggregates with significant redshifts (140–165 nm). The other Pcs fail to form expected J-aggregates probably due to absence of central metals, steric hindrance on central metals (atoms), forming axial coordination on central metals, disorder tendency during self-assembly or hydrophilicity. The theoretical calculation indicates that Pc1 in its J-aggregates exhibits a spiral-like arrangement, and the reduction in the energy gap between HOMO and LUMO and variation of intermolecular π-π interaction caused by J-aggregate formation are responsible for the huge redshift. Additionally, using NanoPc1 as an exemplar, such Pc J-aggregate nanoparticles are substantiated to afford TAMs-targeted and efficient tri-modal imaging and photothermal therapy in a H22 mouse model.

ROS-responsive thioketal nanoparticles delivering system for targeted ulcerative colitis therapy with potent HDAC6 inhibitor, tubastatin A

Ulcerative colitis (UC) is a common gastrointestinal problem characterized by the mucosal injury primarily affecting the large intestine. Currently available therapies are not satisfactory as evidenced by high relapse rate and adverse effects. In this study we aimed to develop an effective drug delivery system using reactive oxygen species (ROS)-responsive thioketal nanoparticles (TKNP), to deliver tubastatin A, a potent HDAC6 inhibitor, to the inflamed colon in mice with ulcerative colitis (UC). TKNPs were synthesized by step-growth polymerization from an acetal exchange reaction while TUBA-TKNP was prepared using the single emulsion solvent evaporation technique. Our developed nanoparticle showed release of tubastatin A only in presence of ROS which is found to be highly present at the site of inflamed colon. Oral administration of TUBA-TKNP resulted in the higher accumulation of tubastatin A at the inflamed colon site and decreased the inflammation as evidenced by reduced infiltration of immune cells and decreased level of pro-inflammatory cytokines in TUBA-TKNP treated mice. In summary, our results show the successful localization of tubastatin A at the site of colon inflammation through TUBA-TKNP delivery, as well as resolution of clinical features of UC in mice.

Construction of recombinant Omp25 or EipB protein loaded PLGA nanovaccines for Brucellosis protection

Safe and effective vaccine candidates are needed to address the limitations of existing vaccines against Brucellosis, a disease responsible for substantial economic losses in livestock. The present study aimed to encapsulate recombinant Omp25 and EipB proteins, knowledged antigen properties, into PLGA nanoparticles, characterize synthesized nanoparticles with different methods, and assessed their in vitro/in vivo immunostimulatory activities to develop new vaccine candidates. The recombinant Omp25 and EipB proteins produced with recombinant DNA technology were encapsulated into PLGA nanoparticles by double emulsion solvent evaporation technique. The nanoparticles were characterized using FE-SEM, Zeta-sizer, and FT-IR instruments to determine size, morphology, zeta potentials, and polydispersity index values, as well as to analyze functional groups chemically. Additionally, the release profiles and encapsulation efficiencies were assessed using UV–Vis spectroscopy. After loading with recombinant proteins, O-NPs reached sizes of 221.2 ± 5.21 nm, while E-NPs reached sizes of 274.4 ± 9.51 nm. The cumulative release rates of the antigens, monitored until the end of day 14, were determined to be 90.39% for O-NPs and 56.1% for E-NPs. Following the assessment of the in vitro cytotoxicity and immunostimulatory effects of both proteins and nanoparticles on the J774 murine macrophage cells, in vivo immunization experiments were conducted using concentrations of 16 µg ml−1 for each protein. Both free antigens and antigen-containing nanoparticles excessively induced humoral immunity by increasing produced Brucella-specific IgG antibody levels for 3 times in contrast to control. Furthermore, it was also demonstrated that vaccine candidates stimulated Th1-mediated cellular immunity as well since they significantly raised IFN-gamma and IL-12 cytokine levels in murine splenocytes rather than IL-4 following to immunization. Additionally, the vaccine candidates conferred higher than 90% protection from the infection according to challenge results. Our findings reveal that PLGA nanoparticles constructed with the encapsulation of recombinant Omp25 or EipB proteins possess great potential to trigger Brucella-specific humoral and cellular immune response.

Formulation and Evaluation of Luliconazole nanosponge gel using Experimental design

Different approaches are being in the practice for the topical application of antifungal drugs, although in a few cases, they have been found less efficient because of their poor cutaneous availability and permeability. Luliconazole (LUL) is one of the antifungal medications that is being used for the treatment of various superficial infections. The poor permeability of LUL is regarded to be a factor for its reduced efficacy. Hence, the current study aimed to develop a nanosponge hydrogel that would improve dermal availability and permeability. A set of nanosponge formulations (L1-L18) were designed with the help of central composite design (Design Expert 13, state ease Inc., Minneapolis, MN, USA). L1-L18 was prepared by using the emulsion solvent evaporation technique. The nanosponges were characterized for drug-excipient compatibility (FTIR, P-XRD, and DSC), and particle size, polydispersibility index, zeta potential, entrapment efficiency (EE), and in vitro drug release; further optimized. The optimized nanosponge formulation (L18) was taken to produce six hydrogels (LF1-LF6) of LUL by varied proportions of the gelling agent. In this process, initially, the gel was constituted with Carbopol 934/ sodium CMC/HPMC. Later, attained hydrogel texture was evaluated for its viscosity, swelling, and membrane permeability, followed by in vitro drug release, and antifungal efficacy study. The nanosponge formulations (L1-L17) had an average particle size of 109±0.45 to 386±0.34 nm, entrapment efficiency of 35.45±0.46- 89.65±0.37 % with 84.67±0.54 -99.65±0.48 % of drug release for 8 h. The formulation L18 was predicted with better responses in particle size, EE, and drug release i.e., 378±0.25 nm, 84.65±0.45%, and of 96.18±0.54%, respectively for 8 h. Out of six formulated nanosponge gels (LF1-LF6), LF2 showed an optimal viscosity (25.69 ±0.45 pa.S), pH (6.87±0.56) and % drug release (80.65 ±0.64%) in 8 h. Drug release was governed by non-fickian diffusion mechanisms and zero-order. Developed nanosponge hydrogel was found as stable and had a high rate of permeation with better retention which can be effective enough in topical applications.

Design of Experiment (DoE) Approach for Developing Inhalable PLGA Microparticles Loaded with Clofazimine for Tuberculosis Treatment.

Tuberculosis (TB) is an airborne bacterial infection caused by Mycobacterium tuberculosis (M. tb), resulting in approximately 1.3 million deaths in 2022 worldwide. Oral therapy with anti-TB drugs often fails to achieve therapeutic concentrations at the primary infection site (lungs). In this study, we developed a dry powder inhalable formulation (DPI) of clofazimine (CFZ) to provide localized drug delivery and minimize systemic adverse effects. Poly (lactic acid-co-glycolic acid) (PLGA) microparticles (MPs) containing CFZ were developed through a single emulsion solvent evaporation technique. Clofazimine microparticles (CFZ MPs) displayed entrapment efficiency and drug loading of 66.40 ± 2.22 %w/w and 33.06 ± 1.45 µg/mg, respectively. To facilitate pulmonary administration, MPs suspension was spray-dried to yield a dry powder formulation (CFZ SD MPs). Spray drying had no influence on particle size (~1 µm), zeta potential (-31.42 mV), and entrapment efficiency. Solid state analysis (PXRD and DSC) of CFZ SD MPs studies demonstrated encapsulation of the drug in the polymer. The drug release studies showed a sustained drug release. The optimized formulation exhibited excellent aerosolization properties, suggesting effective deposition in the deeper lung region. The in vitro antibacterial studies against H37Ra revealed improved (eight-fold) efficacy of spray-dried formulation in comparison to free drug. Hence, clofazimine dry powder formulation presents immense potential for the treatment of tuberculosis with localized pulmonary delivery and improved patient compliance.

PLGA nanocapsules as a delivery system for a recombinant LRP-based therapeutic.

Telomerase activity is directly affected by the laminin receptor precursor (LRP) protein, a highly conserved nonintegrin transmembrane receptor, which has been shown to have therapeutic effects in ageing, and age-related diseases. Recently, it has been found that overexpression of LRP-FLAG, by plasmid transfection, leads to a significant increase in telomerase activity in cell culture models. This may indicate that upregulation of LRP can be used to treat various age-related diseases. However, transfection is not a viable treatment strategy for patients. Therefore, we present a nanoencapsulated protein-based drug synthesised using poly(lactic-co-glycolic acid) (PLGA) nanocapsules for delivery of the 37 kDa LRP protein therapeutic. PLGA nanocapsules were synthesised using the double emulsification-solvent evaporation technique. Different purification methods, including filtration and centrifugation, were tested to ensure that the nanocapsules were within the optimal size range, and the BCA assay was used to determine encapsulation efficiency. The completed drug was tested in a HEK-293 cell culture model, to investigate the effect on cell viability, LRP protein levels and telomerase activity. A significant increase in total LRP protein levels with a concomitant increase in cell viability and telomerase activity was observed. Due to the observed increase in telomerase activity, this approach could represent a safer alternative to plasmid transfection for the treatment of age-related diseases.

Design Optimization and Pharmacokinetic Study of Eletriptan Hydrobromide Loaded Solid Lipid Nanoparticle Nasal Gel Targeted to Brain

In the present research work, Eletriptan Hydrobromide(E-HBr)-loaded solid lipid nanoparticles (SLN’s) incorporated in a gel was prepared by emulsification solvent evaporation technique to enhance the uptake of E-HBr to brain via intra-nasal (i.n.) route and the formulations were evaluated for particle size, polydispersibility index, zeta potential, drug entrapment efficiency, in-vitro drug release, and stability of the optimized formulation. All the parameters evaluated were within the acceptable range. In-vitro drug release for the optimized gel formulation was found to be 92.45% after 12hr and was fitted to the Higuchi model with a very high correlation coefficient (R2=0.995). Pharmacokinetics studies were performed on albino male Wistar rats and the concentration of E-HBr in brain and blood plasma was measured by HPLC. The brain/blood ratio at 0.5h for E-HBr Opt.SLN’s i.n., E-HBr sol. i.n., and E-HBr sol. oral. were found to be 2.35, 1.19 and 0.80 respectively, indicating the drug transported directly from nose-to-brain, by bypassing the blood–brain barrier in the olfactory region present in the nasal cavity. The maximum concentration of drug in brain (Cmax) after i.n. administration of E-HBr-SLN gel was found to be (21465.87±1110.66ng/ml, Tmax 8.45hr) significantly higher than that achieved after oral administration (6797.23±842.86ng/ml, Tmax 7hr), and i.n. (16451.53±3792.40ng/ml, Tmax 7.69 hr) administration of E-HBr sol. The highest drug-targeting efficiency (2.35%) and direct transport percentage (66.05%) was found with E-HBr-SLN’s as compared to the other formulations. Higher DTE (%) and DTP (%) suggest, that E-HBr-SLN gel had better brain targeting efficiency as compared to other formulations.

A Quality By Design (QbD) Prospect in Fabrication of PLGA-based Antipsychotic Long-acting Microspheres: An Alternative to Combination Therapy

Background: Discontinuation and poor compliance with long-term oral medicine are major therapeutic issues in psychosis treatment. Poorer long-term outcomes may result from non-compliance as well as a higher chance of relapse. In order to sustain therapeutic drug plasma levels, co-administration of oral antipsychotics is necessary for commercially available longacting injections of second-generation antipsychotics, as they have a lag period of approximately three weeks during the drug release process. Methods: Poly(lactic-co-glycolic acid) (PLGA) encapsulated microspheres loaded with risperidone were fabricated in the current research for intramuscular administration. The single emulsion solvent evaporation technique was applied for the fabrication of microspheres. Risperidone microspheres were prepared using PLGA grade 75:25. Particle size, drug content and entrapment efficiency with a central composite design were the main optimization parameters for the formulation. The microspheres were characterized by different techniques, namely Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The drug content, entrapment efficiency, morphology, particle size, and in vitro release profiles, along with release kinetics of the risperidone microspheres, were studied. Results and Discussion: The microspheres produced by the single emulsion solvent evaporation approach show smooth and spherical morphology, with particle size ranging from 3 μm to 6 μm, drug content of 99.7%, and entrapment efficiency of 98.2% with little burst release of 3% to 10%, providing drug release for 45 days and exhibiting zero order release kinetics and Korsmeyer- Peppas model for non-fickian drug release from the polymeric matrix. By applying the Quality by Design (QbD) approach and formulation parameters, microspheres with appropriate particle size, morphology, enhanced drug content, entrapment efficiency and desirable drug release profile for depot formulation can be obtained successfully. Conclusion: The optimized microspheres, in comparison to the marketed Risperdal Consta™, show enhanced potential for a better depot formulation, which can further improve patient compliance.

Regulating Tumor-Associated Macrophage Polarization by Cyclodextrin-Modified PLGA Nanoparticles Loaded with R848 for Treating Colon Cancer.

This study aimed to develop a novel and feasible modification strategy to improve the solubility and antitumor activity of resiquimod (R848) by utilizing the supramolecular effect of 2-hydroxypropyl-beta-cyclodextrin (2-HP-β-CD). R848-loaded PLGA nanoparticles modified with 2-HP-β-CD (CD@R848@NPs) were synthesized using an enhanced emulsification solvent-evaporation technique. The nanoparticles were then characterized in vitro by several methods, such as scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, particle size analysis, and zeta potential analysis. Then, the nanoparticles were loaded with IR-780 dye and imaged using an in vivo imaging device to evaluate their biodistribution. Additionally, the antitumor efficacy and underlying mechanism of CD@R848@NPs in combination with an anti-TNFR2 antibody were investigated using an MC-38 colon adenocarcinoma model in vivo. The average size of the CD@R848@NPs was 376 ± 30 nm, and the surface charge was 21 ± 1 mV. Through this design, the targeting ability of 2-HP-β-CD can be leveraged and R848 is delivered to tumor-supporting M2-like macrophages in an efficient and specific manner. Moreover, we used an anti-TNFR2 antibody to reduce the proportion of Tregs. Compared with plain PLGA nanoparticles or R848, CD@R848@NPs increased penetration in tumor tissues, dramatically reprogrammed M1-like macrophages, removed tumors and prolonged patient survival. The new nanocapsule system is a promising strategy for targeting tumor, reprogramming tumor -associated macrophages, and enhancement immunotherapy.

Optimisation of microencapsulation efficiency of propolis phenolic compounds by double emulsion method using response surface methodology

AbstractThe aim of this study was to optimise the microencapsulation efficiency of propolis phenolic compounds by double emulsion solvent evaporation technique (W1/O/W2). The solvent/sample ratio and the polymer and surfactant concentration parameters were optimised using response surface methodology (RSM) through Box–Behnken Design (BBD). For each parameter studied, total phenolic content encapsulation efficiency (TPCEE), free radical scavenging activity (DPPH), and ferric reducing antioxidant power (FRAP) were evaluated. The results showed that the optimal parameters were: 31.60 mg mL−1 for sample/solvent ratio, 606.28 mg mL−1 for poly(ε-caprolactone) (PCL) concentrations, and 2.05 g mL−1 for poly(vinyl alcohol) (PVA) concentration. The optimum values obtained were: 84.62% for encapsulation efficiency of phenolic content, 51.89% for DPPH, and 48,733 mg Trolox Equivalent/100 g dry weight for FRAP. The experimental checking of results revealed the validity of elaborated models and their suitability for the prediction of both responses. The developed mathematical models have expressed a high level of significance through RSM optimisation processes for phenolic antioxidants of propolis.