Fabrication, Optimization, and In Vitro and In Vivo Characterization of Intra-vitreal Implant of Budesonide Generally Made of PHBV.

Drug delivery to vitreous in comparison with drug delivery to the other parts of the eye is complicated and challenging due to the existence of various anatomical and physiological barriers. Developing injectable intra-vitreal implant could be beneficial in this regard. Herein, poly(hydroxybutyrate-co-valerate) (PHBV) implants were fabricated and optimized using response surface method for budesonide (BZ) delivery. The acquired implants were characterized in regard to the stability of the ingredients during fabrication process, drug loading amount, and drug release pattern (in PBS-HA-A and in vitreous medium). According to this research and statistical analysis performed, first HV% (hydroxyvalerate) then molecular weight and ratio of PEG as pore former affect respectively release rate and burst strength of BZ with different coefficients. Drug release profile in rabbit eye correlated well with that of in vitro (R2 = 0.9861, p Ë‚ 0.0001). No significant changes were seen in ERG waves, intraocular pressure, and histological studies during the in vivo part of the project. Using 8% HV, 20% PEG/PHBV, and higher molecular weight PEG (i.e., 6000), the optimum formulation was achieved. Toxicity and biocompatibility of the optimized formulation, which were evaluated in vivo, indicated the suitability of design implant for intra-vitreal BZ delivery. Grapical abstract.

Pharmaceutical implants: classification, limitations and therapeutic applications.

Controlled/sustained delivery systems have been developed rapidly which show the ability to overcome the obstacles of traditional delivery systems. Daily development of biomedical and biomaterial sciences has brought more attention to the implantable delivery systems. As a result, these systems have found their position in the medical field since they were introduced. The advances in the polymeric science along with the other fields, make the production of a wide variety of implantable systems, possible. The influence of these systems in medical field could not be denied Here', the pharmaceutical applications which have been mostly focused on, are discussed. Since these systems have proven to be beneficial, researchers are trying to adjust their defects to the desired properties. Doing so, the path that implantable delivery systems have crossed so far should be studied, and that's the aim of this review. In the present report, the advantages of these systems in chemotherapeutic, contraceptive, neuropsychology, pain management, peptide delivery, ocular delivery, cardiovascular, orthopedic, and dental fields have been evaluated.

Methotrexate and Curcumin co-encapsulated PLGA nanoparticles as a potential breast cancer therapeutic system: In vitro and in vivo evaluation.

Nanoparticulate delivery systems have been noticed for chemotherapeutical delivery due to their ability in controlling the drug release and reducing the side effect. These systems could also be used to deliver two drugs or more simultaneously, inhibiting the development of resistant cancerous cells. Methotrexate (MTX), one of the most frequently used chemotherapeutic agent, and Curcumin (CUR), a natural chemopreventive compound, have shown promising results in treatment or controlling the progression of cancer. The aim of this study is to prepare and evaluate polymeric nanoparticles for co-delivery of MTX and CUR. The PLGA nanoparticles were prepared and characterized in respect of their particles size, morphology, drug encapsulation efficiencies, release patterns, cell cytotoxicity, and in vivo efficacy. Altering MTX and CUR amounts leads to particle size of 142.3 ±â€¯4.07 nm with MTX encapsulation efficiency of 71.32 ±â€¯7.8% and CUR encapsulation efficiency of 85.64 ±â€¯6.3%. These particles showed significantly higher cytotoxicity in comparison with free MTX or CUR or even their solo-loaded formulations. The in vivo results showed the synergic effect of MTX and CUR co-delivery on inhibiting the progression of breast cancer. Considering the appropriate in vitro properties of acquired nanoparticles for controlled drug delivery and the satisfactory in vivo efficacy results, it seems that the prepared formulation is a promising candidate for further in vivo studies.

Improvement of memory deficits in the rat model of Alzheimer's disease by erythropoietin-loaded solid lipid nanoparticles.

Erythropoietin (EPO), a hematopoietic factor, is one of the promising neuroprotective candidates in neurodegenerative disorders such as Alzheimer's disease (AD). Due to the high molecular weight, hydrophilicity and rapid clearance from circulation, EPO could not completely pass the blood-brain barrier in the case of systemic administration. To overcome this limitation, EPO-loaded Solid Lipid Nanoparticle (EPO-SLN) was developed in this study using a double emulsion solvent evaporation method (W1/O/W2). Glycerin monostearate (GMS), span®80/span®60, Dichloromethane (DCM) and tween®80 were chosen as lipid, internal phase surfactants, solvent, and external aqueous phase surfactant, respectively. After physicochemical evaluations, the effect of EPO-SLN on the beta-amyloid-induced AD-like animal model was investigated. In vivo evaluations, it was demonstrated that the memory was significantly restored in cognitive deficit rats treated with EPO-SLN compared to the rats treated with native drug using the Morris water maze test. In addition, EPO-SLN reduced the oxidative stress, ADP/ATP ratio, and beta-amyloid plaque deposition in the hippocampus more effectively than the free EPO. Hence, the designed SLN can be regarded as a promising system for safe and effective delivery of EPO in the AD.

Erythropoietin-loaded solid lipid nanoparticles: Preparation, optimization, and in vivo evaluation.

Solid lipid nanoparticle (SLN) is a promising approach for delivery of various drugs including proteins and peptides. However, the loading of hydrophilic drugs into the lipoid matrix of SLNs is challenging. The statistical design is a potential method facilitating the optimization of nanoparticles characteristics. In this study, the Box-Behnken design was conducted to optimize the preparation of Erythropoietin (EPO) loaded SLNs. Circular dichroism, size exclusion chromatography, SDS-PAGE, and ELISA tests were used to prove the compatibility of the process with the stability of EPO. In the controlled situation, EPO preserved its conformation and activity during the SLN preparation. Regarding the particle size, entrapment efficiency, and polydispersity index, an optimum formulation was obtained with 130 mg Span®80, 152.5 µl EPO, and 1.9 min high-shear homogenization. Using the optimum condition, 280 nm sized SLNs with the narrow size distribution of 0.282 and entrapment efficiency of 43.4% were acquired. The in vitro cytotoxicity of optimum SLN formulation was conducted using MTT assay to show its safety on the evaluated cell line. The in vivo studies demonstrated that 2500 U EPO loaded SLN has similar or even better effects on elevating the RBC, hemoglobin, and hematocrit level compared to the 5000 U EPO solution. Generally, this study proposed a suitable EPO-loaded SLN preparation method as a potential drug delivery system for proteins.

Nicotinamide loaded functionalized solid lipid nanoparticles improves cognition in Alzheimer's disease animal model by reducing Tau hyperphosphorylation.

BACKGROUND: Nicotinamide is considered to be effective in halting the Alzheimer's disease progression. The body could absorb a limited amount of nicotinamide at a time, requiring multiple doses through a day. To overcome such an obstacle which reduces the patient compliance, a sustained/controlled delivery system could be useful. METHOD: Nicotinamide loaded solid lipid nanoparticles (SLN) were prepared and functionalized with polysorbate 80 (S80), phosphatidylserine (PS) or phosphatidic acid (PA). The acquired particles were characterized and evaluated in respect of their cytotoxicity, biodistribution, and in vivo effectiveness through the different routes of administration. RESULTS: The optimum sizes of 112 ± 1.6 nm, 124 ± 0.8 nm, and 137 ± 1.05 nm were acquired for S80-, PS-, and PA-functionalized SLNs, respectively. The in vitro cytotoxicity on SH-SY5Y cell line showed the safety of formulations except for S80-functionalized SLNs. Biodistribution study of SLNs has proved the benefits of functionalization in improving the brain delivery. The results of spatial and memory test, i.e. Morris water maze, and also histopathology and biochemical tests demonstrated the effectiveness of i.p. injection of PS -functionalized SLNs in improving the cognition, preserving the neuronal cells and reducing tau hyperphosphorylation in a rat model of Alzheimer's disease. CONCLUSION: The acquired PS-functionalized SLN could be a potential brain delivery system. Loaded with nicotinamide, an HDAC inhibitor, it could ameliorate the cognition impairment of rats more effectively than the conventional administration of nicotinamide, i.e. oral, in the early stage of Alzheimer's disease. Graphical abstract ᅟ.

Application of Response Surface Method for Preparation, Optimization, and Characterization of Nicotinamide Loaded Solid Lipid Nanoparticles.

Purpose: Solid lipid nanoparticles (SLNs) have been proven to possess pharmaceutical advantages. They have the ability to deliver hydrophilic drugs through lipid membranes of the body. However, the loading of such drugs into SLNs is challenging. Hydrophilic nicotinamide, a histone deacetylase inhibitor, is used to establish SLNs with enhanced encapsulation efficiency by using statistical design. Methods: The possible effective parameters of these particles' characteristics were determined using pre-formulation studies and preliminary tests. Afterwards, the Response Surface Method (RSM) was utilized to optimize the preparation condition of SLNs. The effect of the amount of lipid, drug, surfactant, and the mixing apparatus were studied on particle size, zeta potential, and encapsulation efficiency of the obtained particles. The acquired particles were characterized in respect of their morphology, in vitro release profile, and cytotoxicity. Results: According to this study, all the dependant variables could be fitted into quadratic models. Particles of 107 nm with zeta potential of about -40.9 and encapsulation efficiency of about 36% were obtained under optimized preparation conditions; i.e. with stearic acid to phospholipon® 90G ratio of 7.5 and nicotinamide to sodium taurocholate ratio of 14.74 using probe sonication. The validation test confirmed the model's suitability. The release profile demonstrated the controlled release profile following the initial burst release. Neither the nicotinamide nor the SLNs showed toxicity under the evaluated concentrations. Conclusion: The acquired results suggested the suitability of the model for designing the delivery system with a highly encapsulated water soluble drug for controlling its delivery.

Development, evaluation and optimization of superparamagnetite nanoparticles prepared by co-precipitation method.

Magnetic nanoparticles (MNPs) are of high interest due to their application in medical fields, in particular for theranostics. Specific properties required for such particles include high magnetization, appropriate size and stability. Biocompatible magnetically soft magnetite particles (Fe3O4) have been investigated for biological purposes. The intrinsic instability of these nanoparticles and their susceptibility to the oxidization in air, are limitations for their applications. Various methods have been described for synthesis of these nanoparticles among which co-precipitation method is widely experimented. In order to illustrate the synthesis of MNPs elaborately, the effect of different factors on particle formation were studied. The particles morphology, stability, paramagnetic effect, chemical structure and cytotoxicity were evaluated. Particles of 58 and 60 nm obtained by oleic acid coated (OMNPs) and citric acid coated (CMNPs) magnetite nanoparticles respectively. Transmission electron microscopy images exhibited the real sizes are 15 and 13 nm. Magnetic saturations of these nanoparticles were 72 and 68 emu/g which is suitable for medical applications. Both OMNPs and CMNPs were non-toxic to the SK-Br-3 and MCF-7 cells in the concentrations of <2.5 µg/mL. Since these particles exhibit relatively high magnetic saturation, low dose of such material would be required; therefore, these NPs seem to be suitable for theranostics.