Cold Homogenization Research Articles

Recent Advances in the Preparation, Properties, and Applications of Solid Lipid Nanoparticles in Drug Delivery

Solid lipid nanoparticles (SLNs) are one of the extensively utilized nanocarriers in the pharmaceutical field due to their biocompatibility and biodegradability. These features of the carrier system have fuelled its use as the drug delivery system since the last three decades. This review presents different SLN preparation techniques, such as high shear homogenization, hot homogenization, cold homogenization, microemulsion-based technique, etc. The physicochemical nature of SLNs, comprising drug loading, drug release, particle size, zeta potential, stability, cytotoxicity, and cellular uptake, has been concisely discussed. The article also explains why SLNs are preferred to develop drug delivery systems in several pharmaceutical preparations. The key ingredients like lipid, surfactant/ stabilizer accompanied by co-surfactant, cryoprotectant, or charge modifiers used to fabricate SLNs are also briefly conferred. Here is an elaborate discussion of drugs that are used through various routes by the SLN carrier system and their outcome for utilization of this system. Regulatory aspects, patent aspects, and future prospects of SLN are also discussed here.

Lipid-Based Nanocarrier by Targeting with LHRH Peptide: A Promising Approach for Prostate Cancer Radio-Imaging and Therapy.

Prostate cancer is a prevalently detected malignancy with a dismal prognosis. Luteinizing-hormone-releasing-hormone (LHRH) receptors are overexpressed in such cancer cells, to which the LHRH-decapeptide can specifically bind. A lipid-polyethylene glycol-conjugated new LHRH-decapeptide analogue (D-P-HLH) was synthesized and characterized. D-P-HLH-coated and anticancer drug doxorubicin (DX)-loaded solid lipid nanoparticles (F-DX-SLN) were formulated by the cold homogenization technique and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, differential scanning calorimetry, dynamic light scattering, electron microscopy, entrapment efficiency, and drug-release profile studies. F-DX-SLN allows site-specific DX delivery by reducing the side effects of chemotherapy. Cancer cells could precisely take up F-DX-SLN by targeting specific receptors, boosting the cytotoxicity at the tumor site. The efficacy of F-DX-SLN on PC3/SKBR3 cells by the MTT assay revealed that F-DX-SLN was more cytotoxic than DX and/or DX-SLN. Flow cytometry and confocal microscopic studies further support F-DX-SLNs' increased intracellular absorption capability in targeting LHRH overexpressed cancer cells. F-DX-SLN ensured high apoptotic potential, noticeably larger mitochondrial transmembrane depolarization action, as well as the activation of caspases, a longer half-life, and greater plasma concentration. F-DX-SLN/DX-SLN was radiolabeled with technetium-99m; scintigraphic imaging studies established its tumor selectivity in PC3 tumor-bearing nude mice. The efficacy of the formulations in cancer treatment, in vivo therapeutic efficacy tests, and histopathological studies were also conducted. Results clearly indicate that F-DX-SLN exhibits sustained and superior targeted administration of anticancer drugs, thus opening up the possibility of a drug delivery system with precise control and targeting effects. F-DX-SLN could also provide a nanotheranostic approach with improved efficacy for prostate cancer therapy.

Solid Lipid Nanoparticles: A Review of their Biomedical Applications and Preparation.

Solid lipid nanoparticles (SLNs) are gaining significant attention in the pharmaceutical industry due to their biocompatibility and biodegradability, making them a popular functional nanocarrier. SLNs are a popular nanocarrier due to their ability to bypass the spleen and liver, offer high drug stability, and improve bioavailability, sterilization, immobilization, targeted drug release, and biocompatible ingredients. This article discusses various SLN preparation techniques, including high shear homogenization, hot homogenization, cold homogenization, microemulsion-based, solvent evaporation, solvent emulsification-evaporation, supercritical fluid-based, spray drying, double emulsion, and precipitation techniques, focusing on methodological aspects. This review discusses the physicochemical behavior of SLNs, including drug loading, release, particle size, stability, cytotoxicity, and cellular uptake, and their major biomedical applications.

Изучение эволюции микроструктуры и механических свойств в алюминиевом сплаве 1570 с добавкой 0,5 % гафния

Introduction. Aluminum alloys are in high demand with the aerospace industry. From the viewpoint of various performance characteristic combinations, high-magnesium aluminum alloys with the addition of transition metals, such as Zr and Sc, are among the most future-oriented alloys. Alloy 1570 is one of the most popular in this group. Recent studies demonstrated the positive effect of 0.5 % hafnium addition on as-cast structure. Study objective is to study the effect of the addition of 0.5% hafnium on the structure and properties of aluminum alloy 1570 during thermomechanical treatment. The study addresses the effect of cold rolling, homogenization, and recrystallization annealing on mechanical properties and microstructure of the specimens from alloy 1570 and similar alloy with 0.5 wt. % hafnium addition. Study methodology: for the study, ingots were cast from alloy 1570 with and without additions of 0.5 wt. % of hafnium. The resulting ingots were homogenized for 4 h at 440 °С, followed first by hot rolling and then cold rolling. Cold-rolled specimens were annealed at temperatures 340 °С to 530 °С with a holding time of 3 hours. The homogenized, cold-rolled, and annealed specimens were examined using transmission and light microscopy. In addition, homogenized and cold-rolled specimens were subjected to uniaxial tensile tests to determine the mechanical properties of the studied alloy. Results and discussion. It is revealed that in an alloy containing hafnium, after homogenization annealing, there is a slight decrease in the average particle size and an increase in its total proportion in comparison with alloy 1570. In general, 0.5 % hafnium addition does not significantly affect the mechanical properties. The number of nanoparticles in both alloys increases, as does the yield strength compared to the as-cast state. When heated, both alloys demonstrate an increase in plasticity and a decrease in strength characteristics. Studies of the annealing effect on the grain structure of the studied alloys showed that hafnium increases the tendency of alloy 1570 to recrystallize. However, additional research is required to determine the reasons for this phenomenon.

Biological evaluation of novel gemcitabine analog in patient-derived xenograft models of pancreatic cancer

Gemcitabine (Gem) has been a standard first-line drug for pancreatic cancer (PCa) treatment; however, Gem's rapid metabolism and systemic instability (short half-life) limit its clinical outcome. The objective of this study was to modify Gem into a more stable form called 4-(N)-stearoyl-gemcitabine (4NSG) and evaluate its therapeutic efficacy in patient-derived xenograft (PDX) models from PCa of Black and White patients.Methods 4NSG was synthesized and characterized using nuclear magnetic resonance (NMR), elemental analysis, and high-performance liquid chromatography (HPLC). 4NSG-loaded solid lipid nanoparticles (4NSG-SLN) were developed using the cold homogenization technique and characterized. Patient-derived pancreatic cancer cell lines labeled Black (PPCL-192, PPCL-135) and White (PPCL-46, PPCL-68) were used to assess the in vitro anticancer activity of 4NSG-SLN. Pharmacokinetics (PK) and tumor efficacy studies were conducted using PDX mouse models bearing tumors from Black and White PCa patients.Results 4NSG was significantly stable in liver microsomal solution. The effective mean particle size (hydrodynamic diameter) of 4NSG-SLN was 82 ± 6.7 nm, and the half maximal inhibitory concentration (IC50) values of 4NSG-SLN treated PPCL-192 cells (9 ± 1.1 µM); PPCL-135 (11 ± 1.3 µM); PPCL-46 (12 ± 2.1) and PPCL-68 equaled to 22 ± 2.6 were found to be significantly lower compared to Gem treated PPCL-192 (57 ± 1.5 µM); PPCL-135 (56 ± 1.5 µM); PPCL-46 (56 ± 1.8 µM) and PPCL-68 (57 ± 2.4 µM) cells. The area under the curve (AUC), half-life, and pharmacokinetic clearance parameters for 4NSG-SLN were 3–fourfold higher than that of GemHCl. For in-vivo studies, 4NSG-SLN exhibited a two-fold decrease in tumor growth compared with GemHCl in PDX mice bearing Black and White PCa tumors.Conclusion 4NSG-SLN significantly improved the Gem's pharmacokinetic profile, enhanced Gem's systemic stability increased its antitumor efficacy in PCa PDX mice bearing Black and White patient tumors.

Improvement of Entrapment and Ocular Permeability of Ganciclovir Nanostructured Lipid Carriers Using Various Conditions of Preparations

Ganciclovir (GCV) is a drug included in BCS-Class III, having high solubility and low permeability. It is a synthetic acyclic nucleoside analog of 2′-deoxyguanosine, considered a potent inhibitor of herpes viruses and cytomegalovirus (CMV) infection. Herpes simplex virus (HSV) infections are very common and are also considered a major cause of corneal blindness. This study intended to advance a pioneering nanostructured lipid carriers (NLCs) system for improving the ocular permeability of GCV. Several procedures were used for the preparation. Cold homogenization, solvent injection, and emulsifi cationultrasonication methods. A mixture of palmitic acid (PA) and oleic acid (OA) as a lipid matrix, cremophore EL, and transcutol HP were used as emulsifi ers. To evaluate the optimum method, the particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment effi ciency (EE), and drug loading (DL%) were determined for the prepared NLCs. Due to the decreased particle size value, the polydispersity index, and the high value of EE%, emulsifi cation/ultrasonication outcomes were more practical than cold homogenization and solvent injection procedures. The fi ndings demonstrated that the preparation procedure had a substantial impact on the EE%.The emulsifi cation method can prepare the NLCs of GCV successfully.

The effect of combined cold rolling and homogenization on the microstructures and mechanical properties of twin-roll casted 8021 aluminum alloy

The microstructures and mechanical properties of the twin-roll casting (TRC) 8021 alloy strip under different homogenization processes (direct homogenization, cold rolling + homogenization) have been systematically investigated by optical microscope, tensile testing, scanning electron microscopy (SEM) and electron backscattered diffraction (EBSD) technique. It was revealed that due to the severe microstructural gradient throughout the full strip thickness, the coarse grain layer is readily formed in the strip surface due to the high stored energy involved. Although the introduction of cold rolling before homogenization reduces the strain inhomogeneity in the strip, the rather high deformation level produces fully recrystallized structures after homogenization at 580 °C. After cold rolling and final annealing, recrystallized grains are formed in the interior of the sheets for most the homogenization temperatures. Compared with direct homogenized samples, the average recrystallized grain sizes in the “cold-rolled + homogenized” samples are larger due to the small thickness reduction. Therefore, the combination of cold rolling and homogenization can improve the elongation and decrease the strength of the strip. Homogenization at 530 °C is selected as the optimum parameter for both the two homogenization processes as it provides a good combination of strength and elongation.

Nanostructured Lipid Carriers: A Vital Drug Carrier for Migraine Treatment

Migraine is a very mysterious and much-misunderstood disorder characterized by pulsating headache in one side of the head in the form of attacks lasting from 4-48 hrs. It is a complex neurological condition, in this condition which can affect the whole body with many symptoms. However to cure this and effective treatment the nanostructured lipid carriers are used as widely nowadays. This use of structures ranges from the size 1-100nm with the main aim to develop the medicine to diagnose as accurately and effectively with less or no side effects. As we developed the stability and leakage of drugs is also improved. As we know the limitations from the different routes of administration are first-pass metabolism, poor bioavailability, and poor solvency to overcome these limitations Nanostructured lipid carriers (NLCs) were prepared. Transdermals, ocular, oral, topical, and parenteral are the different routes through which Nano based systems are delivered. Spatially incompatible liquid lipids and solid lipids are blended and NLCs were prepared. The main advantages of drug therapy over conventional carriers NLCs are improved bioavailability, increased solubility. This review describes the NLC used for the migraine treatments, its advantages, and disadvantages, types, NLC techniques, mode of action, of NLC. Imperfect, amorphous, and multiple types are the main three types of NLCs. Lipids like solid and liquid, Emulsifiers, and aqueous medium were the excipients used. Micro-emulsion technique, micro-emulsion-based SLN/NLC preparations, solvent diffusion method, high-pressure homogenization (HPH), hot and cold homogenization techniques, and melt emulsification method are the techniques used for the preparation of NLC.

The Effect of Combined Cold Rolling and Homogenization on the Microstructures and Mechanical Properties of Twin-Roll Casted 8021 Aluminum Alloy

The Effect of Combined Cold Rolling and Homogenization on the Microstructures and Mechanical Properties of Twin-Roll Casted 8021 Aluminum Alloy

The Depigmentation Effect of Hydroquinone-loaded Nanostructured Lipid Carriers (NLCs) on the Rat Skin

The goal of this research is the localization of hydroquinone (HQ) to the epidermis for the treatment of hyperpigmentation in rat skin. For this purpose, nanostructured lipid carrier (NLC) was selected for the dermal delivery of HQ. A 23 factorial design was used in this study, and eight NLCs were prepared with a cold homogenization technique. HQ entrapment efficiency (EE %), particle size, morphology, thermal behavior of NLCs, and permeability parameters through rat skin with NLC in comparison with HQ aqueous solution (HQ-S) with Franz diffusion cells were evaluated. Based on the optimization technique, the best NLC was selected and in the in vivo experiment, the depigmentation effect of optimized NLC in comparison with that of HQ-S was evaluated. The results showed that the main problem for HQ permeability was fast permeation and low concentration in the site of action. Partitioning from aqueous donor phase into skin rate was the limiting step for drug flux, and this can be solved using NLC. The decrease in maximum flux obtained by NLC was according to formulation 8. Regression analysis suggested a significant and direct effect of the S/L ratio and the percentage of liquid lipids on the drug loading. NLC decreased drug permeation through rat skin basically due to sustained release properties.

Topical ocular delivery of vancomycin loaded cationic lipid nanocarriers as a promising and non-invasive alternative approach to intravitreal injection for enhanced bacterial endophthalmitis management

Vancomycin (VCM) is a drug of choice for treating infections caused by Staphylococcus species, reported being the most causative agent of bacterial endophthalmitis. However, the ocular bioavailability of topically applied VCM is low due to its high molecular weight and hydrophilicity. The current study sought to explore whether the nanostructured lipid carriers (NLCs) fabricated via cold homogenization technique could improve ocular penetration and prolong the ophthalmic residence of VCM. A 23 full factorial design was adopted to evaluate the influence of different process and formulation variables on VCM-loaded NLC formulae. The optimized formula with the particle size of 96.4 ± 0.71 nm and narrow size distribution showed spherical morphology obtained by AFM and represented sustained drug release up to 67% in 48 h fitted to the Korsmeyer-Peppas model with probably non-Fickian diffusion kinetic. FTIR studies visualized the drug-carrier interactions in great detail. High encapsulation of VCM (74.8 ± 4.3% w/w) in NLC has been established in DSC and PXRD analysis. The optimal positively charged (+ 29.7 ± 0.47 mV) colloidal dispersion was also stable for 12 weeks at both 4 °C and 25 °C. According to in vivo studies, incorporation of VCM in NLC resulted in a nearly 3-fold increase in the intravitreal concentration of VCM after eye-drop instillation over control groups. Besides, microbiological evaluation admitted its therapeutic effect within five days is comparable to intravitreal injection of VCM. Further, the optimized formula was found to be nonirritant and safe for ophthalmic administration in RBC hemolytic assay. Also, fluorescent tracking of NLCs on rabbit's cornea showed an increase in corneal penetration of nanoparticles. Thus, it is possible to infer that the evolved NLCs are promising drug delivery systems with superior attainments for enhanced Vancomycin ophthalmic delivery to the eye's posterior segment and improved bacterial endophthalmitis management.

Pharmaceutical and Pharmacological Evaluation of the Effect of Nano-Formulated Spironolactone and Progesterone on Inflammation and Hormonal Levels for Managing Hirsutism Experimentally Induced in Rats.

Hirsutism is a dermatological condition that refers to the excessive growth of hair in androgen-sensitive areas in women. Recently, the enhancement of the visible signs of a hairy female has taken special concern that affected the quality of life. The present study was developed to compare the follicular targeting effect of topical spironolactone (SP) or progesterone (PG)-loaded nanostructured lipid carrier (NLC) on the management of hirsutism. Four NLC formulations were prepared using cold homogenization techniques and pharmaceutically evaluated. SP-NLC and PG-NLC topical hydrogels were prepared to explore their pharmacological effect on letrozole induced polycystic ovarian syndrome (PCOS) in rats. Inflammatory mediators, antioxidant, and hormonal parameters were assayed. Additionally, histopathological examination was carried out to confirm the successful induction of PCOS. Results confirmed that all NLC formulations have a spherical shape with particle size ranged from 225.92 ± 0.41 to 447.80 ± 0.66 nm, entrapment efficiency > 75%, and zeta potential (- 31.4 to - 36.5 mV). F1 and F3 NLCs were considered as selected formulations for SP and PG, respectively. Female Wistar rats treated with F1 formulation for 3 weeks displayed better outcomes as manifested by the measured parameters as compared to the other tested groups. A significant reduction in hair follicle diameter and density was observed after topical application of SP or PG nano-gels. Finally, the outcomes pose a strong argument that the development of topically administered SP-NLC can be explored as a promising carrier over PG-NLC for more effectual improvement in the visible sign of hirsutism.

Preparation and characterization of topical solid lipid nanoparticles containing deferoxamine

Introduction: Deferoxamine mesylate increases hypoxia inducible factor-1 alpha transactivation by preventing iron-catalyzed reactive oxygen stress, so it can be used to improve diabetic ulcer healing. This study was undertaken to develop and study physicochemical properties of topical deferoxamine-loaded solid lipid nanoparticles.
 Method: Solid lipid nanoparticles were prepared using cold homogenization technique and full factorial design to evaluate the effect of surfactant type and amount of lipid. In-vitro characterization of formulations including particle size and distribution, thermal behavior using Differential Scanning Calorimetry, entrapment efficiency, and release profile were carried out.
 Results: The results showed an acceptable range of particle size (2.88–174 nm), a narrow size distribution, and an average of 60% for drug entrapment efficiency which is significant for a hydrophilic drug. The results from release study showed an initial burst release followed by a slow and prolonged manner. Differential Scanning Calorimetry results also confirmed the results obtained from loading and release evaluations. The best formulation which had a high level of drug loading and the lowest drug release rate contained compritol and oleic acid in the amount of 8% of the total formula, as well as tween 80 and lecithin as a mixture of surfactants.
 Conclusions: The study demonstrated deferoxamine could be loaded in solid lipid nanoparticles to deliver topically.

Formulation Design and <i>in vitro-in vivo</i> Evaluation of Sustained Release Aspirin Microparticles Based on PEGylated Lipids

Background: PEGylation is a strategy that on therapeutic molecules such as drugs, proteins and macromolecules, in order to improve their delivery. It has this unique property of increasing the size and molecular weight of biomolecules that are conjugated in nature in order to improve water solubility, reduction in renal clearance and protects the drug from enzymatic degradation. Objectives: The objectives of this work was to formulate sustained release aspirin-loaded solid lipid microparticles based on PEGylated lipid matrix, to evaluate the <i>in-vitro</i> properties of the SLM and to study the anti-inflammatory and ulcerogenic properties of the SLM. Methods: Aspirin-loaded solid lipid microparticles (SLMs) were formulated by cold homogenization method. Furthermore, they were analyzed for the encapsulation efficiency, <i>in-vitro</i> release, particle size, anti-inflammatory and ulcer inhibition properties. Results: Particle size ranged from 9.36±2.63 to 16.77±5.80 µm for batches B₁ to D₁ SLMs loaded with 10% LM, 5% PEG 4000 and 0.25-1% aspirin respectively, while batches B₂ to D₂ formulated with 10% LM, 10% PEG and 0.25 -1% aspirin had particle size range of 9.09±4.03 to 15.71±10.09 µm. Batches D₁ containing 1% of aspirin had the highest encapsulation efficiency of 58%. Maximum <i>in-vitro</i> release of 29.20% and 15.85% were obtained at 6 h for batches D₁ and B₂ respectively. SLMs showed an average of 66.67 – 83.3% oedema inhibition, while the reference had 50%, and ulcer inhibition of 75% for batch D₁. Conclusion: Due to the good properties exhibited by the aspirin-loaded SLMS, they could be used for the treatment of inflammation.

Formulation and characterization of artemether-loaded sodium alginate microcapsules

Purpose: To increase the solubility of artemether (ART) in Transcutol® HP through microencapsulation in sodium alginate polymer to achieve sustained in vivo release.Method: Graded concentrations of ART (0.00, 0.25, 0.50, 0.75, and 1.00 g) microcapsules were produced using Tween® 80 by the cold homogenization method at 24 x 1000 rpm for 15 min. Characterization based on yield, encapsulation efficiency (EE), particle size, pH stability, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and in vivo release using Peter’s four-day suppressive protocol in Wistar mice infected with Plasmodium berghei, were determined.Results: The results obtained indicate that 0.5 g ART-loaded microcapsules (AMC) showed the highest yield of 96.85 %. The EE of 88.3 % corresponded to 0.75 g ART-loaded microcapsules. DSC results revealed that there was a significant reduction in enthalpy in all the formulations compared to the crystalline drug, but no strong bond interaction occurred except for the blank microcapsules. The AMC1.0 showed high dose-dependent plasmodial growth inhibition of 88.75 % while AMC0.25 had the least (68.13 %).Conclusion: The artemether microcapsules showed sustained release characteristics for oral delivery of artemether and therefore may reduce some of the adverse effects associated with high dose artemether therapy in conventional oral tablets.&#x0D; Keywords: Malaria, Artemether, Transcutol® HP, Sustained-release, RBC count, Antiplasmodial activity

Application of smart solid lipid nanoparticles to enhance the efficacy of 5-fluorouracil in the treatment of colorectal cancer

5-Fluorouracil (5-FU) is a standard treatment option for colorectal cancer (CRC) but its rapid metabolism and systemic instability (short half-life) has hindered its therapeutic efficacy. The objective of this study was to develop a novel drug delivery system, solid lipid nanoparticle (SLN), capable of delivering high payload of 5-FU to treat CRC. The rational was to improve 5FU-nanocarrier compatibility and therapeutic efficacy. The SLN-loaded 5-FU was developed by utilizing a Strategic and unique Method to Advance and Refine the Treatment (SMART) of CRC through hot and cold homogenization approach. The SLN was made of unique PEGylated lipids and combination of the surfactants. Cytotoxicity studies, clonogenic assay, flow cytometry and confocal imaging were conducted to evaluate the effectiveness and cellular uptake of 5FU-SLN4 in HCT-116 cancer cells. Pharmacokinetic (PK) parameters and receptor expressions were determined while tumor efficacy studies were conducted on mouse bearing subcutaneous HCT-116 cancer. Among the all the formulations, 5FU-SLN4 was the most effective with particle size of was 263 ± 3 nm, zeta potential was 0.1 ± 0.02 and entrapment efficiency of 81 ± 10%. The IC50 value of 5FU-SLN4 (7.4 ± 0.02 µM) was 2.3 fold low compared with 5-FU (17.7 ± 0.03 µM). For tumor efficacy studies, 5FU-SLN4 significantly inhibited tumor growth in comparison to 5-FU while area-under plasma concentration-time curve (AUC) of 5FU-SLN4 was 3.6 fold high compared with 5-FU. HER2 receptors expression were markedly reduced in 5-FU-SLN4 treated mice compared with 5FU and liver and kidney tissues showed no toxicity at dose of 20 mg/kg. 5FU-SLN4 was highly cytotoxic against HCT-116 cells and significantly inhibited subcutaneous tumor growth in mice compared with 5-FU. This emphasizes the significance of developing a smart nano-delivery system to optimize the delivery efficiency of anticancer drugs to tumors.

Formulation and Development of Pantothenic Acid Grafted Solid Lipid Nanoparticle for Site Specific Delivery of Chloroquine

Chloroquine phosphate (CQP) is one of the widely used drug in treatment of malaria. The use of CQP is declining due to development of resistance and plethora of side effects. SLNs were prepared by cold homogenization technique after applying the 32 level factorial design and grafted with ligand pantothenic acid for site specificity. The prepared formulations were evaluated for different physicochemical properties and were found to be spherical in shape with a size ranging between 92.25 ± 0.54 nm with polydispersity index of 1.15 ± 0.12, which is an ideal size for intravenous administration. The zeta potential of the SLNs was found to be +7.78 ± 0.12 mV. The entrapment efficiency was found to be greater than 94.51 ± 1.19% w/w. The in-vitro drug release studies showed a sustained drug release from the lipid matrix which was below 59.8% within 72 hrs. Furthermore, in-vitro erythrocyte toxicity test was performed on SLNs and pure drug. The study revealed that the encapsulated CQP showed lesser haemolysis (24.5 %) compared to pure drug (62.41± 0.16 %). These findings suggests that the encapsulated drug showed lesser haemolytic activity and thus can reduce the side effects associated with drug administration by direct intravenous route.

Formulation, optimization, and in vitro evaluation of nanostructured lipid carriers for topical delivery of Apremilast.

This work was aimed to formulate topical Apremilast (APM)-loaded nanostructured lipid carriers (NLCs) for the management of psoriasis. NLCs were prepared by a cold homogenization technique using Compritol 888ATO, oleic acid, Tween 80 and Span 20, and Transcutol P as a solid lipid, liquid lipid, surfactant mixture, and penetration enhancer, respectively. Carbopol 940 was used to convert NLC dispersion into NLC-based hydrogel to improve its viscosity for topical administration. The optimized formulation was characterized for size, polydispersity index (PDI), zeta potential (ZP), percentage of entrapment efficiency (%EE), and surface morphology. Furthermore, viscosity, spreadability, stability, in vitro drug diffusion, ex vivo skin permeation, and skin deposition studies were carried out. APM-loaded NLCs showed a narrow PDI (0.339) with a particle size of 758 nm, a %EE of 85.5%, and a ZP of -33.3 mV. Scanning electron microscopy confirmed spherical shape of NLCs. in vitro drug diffusion and ex vivo skin permeation results showed low drug diffusion, sustained drug release, and 60.1% skin deposition. The present study confirms the potential of the nanostructured lipid form of poorly water-soluble drugs for topical application and increased drug deposition in the skin.

Formulation and Intracellular Trafficking of Lipid-Drug Conjugate Nanoparticles Containing a Hydrophilic Antitubercular Drug for Improved Intracellular Delivery to Human Macrophages.

Isoniazid is an important first-line antitubercular drug used in the treatment of all major clinical manifestations of tuberculosis, including both pulmonary and cerebral diseases. However, it is associated with significant drawbacks due to its inherent hydrophilic nature, including poor gut permeability and an inability to cross the lipophilic blood–brain barrier, which, in turn, limit its clinical efficacy. We hypothesized that the addition of a hydrophobic moiety to this molecule would help overcome these limitations and improve its bioavailability in the bloodstream. Therefore, we designed a stable, covalently linked lipid–drug conjugate of isoniazid with a short lipid chain of stearoyl chloride. Further, lipid–drug conjugate nanoparticles were synthesized from the bulk lipid–drug conjugate by a cold high-pressure homogenization method enabled by the optimized use of aqueous surfactants. The nanoparticle formulation was characterized systematically using in vitro physicochemical analytical methods, including atomic force microscopy, transmission electron microscopy, differential scanning calorimetry, X-ray diffraction, attenuated total reflectance, particle size, ζ-potential, and drug release studies, and the mechanism of drug release kinetics. These investigations revealed that the lipid–drug conjugate nanoparticles were loaded with an appreciable amount of isoniazid conjugate (92.73 ± 6.31% w/w). The prepared lipid–drug conjugate nanoparticles displayed a uniform shape with a smooth surface having a particle size of 124.60 ± 5.56 nm. In vitro drug release studies showed sustained release up to 72 h in a phosphate-buffered solution at pH 7.4. The release profile fitted to various known models of release kinetics revealed that the Higuchi model of diffusion kinetics was the best-fitting model (R2 = 0.9929). In addition, confocal studies showed efficient uptake of lipid–drug conjugate nanoparticles by THP-1 macrophages presumably because of increased lipophilicity and anionic surface charge. This was followed by progressive intracellular trafficking into endosomal and lysosomal vesicles and colocalization with intravesicular compartmental proteins associated with mycobacterium tuberculosis pathogenesis, including CD63, LAMP-2, EEA1, and Rab11. The developed lipid–drug conjugate nanoparticles, therefore, displayed significant ability to improve the intracellular delivery of a highly water-soluble drug such as isoniazid.

Effects of Myricitrin and Solid Lipid Nanoparticle-Containing Myricitrin on Reproductive System Disorders Induced by Diabetes in Male Mouse.

PurposeThe present study investigates the effects of myricitrin and solid lipid nanoparticle (SLN) containing myricitrin on the reproductive system of type 2 diabetic male mice.Materials and MethodsIn this experimental study, SLN containing myricitrin was prepared by the cold homogenization method. Then, 90 adult male Naval Medical Research Institute mice were divided into 9 groups (n=10): control, vehicle, diabetic, diabetic+myricitrin or SLN containing myricitrin 1, 3, and 10 mg/kg. Diabetes was induced by streptozotocin (65 mg/kg) 15 minutes after nicotinamide (120 mg/kg) injection. Myricitrin and SLN containing myricitrin administered during 1 month. At the 34th days of the experiment, plasma and tissue samples were taken for experimental assessments.ResultsTestis weight and volume decreased in the diabetic group. These variables increased in diabetic treated mice by a high dose of myricitrin or all doses of SLN containing myricitrin (p<0.05). Total antioxidant capacity and superoxide dismutase levels decreased in diabetic mice, and administration of myricitrin 10 mg/kg or all doses of SLN containing myricitrin increased them (p<0.05). Luteinizing hormone, Follicle-stimulating hormone, testosterone, and sperm count decreased in the diabetic group, treatment with a high dose of myricitrin or all doses of SLN containing myricitrin recovered them (p<0.05). Diabetes induced vacuoles and apoptosis in testicular cells, meanwhile myricitrin and SLN containing myricitrin improved them (p<0.05).ConclusionsDiabetes induced reproductive problem via increased oxidative stress and decrease antioxidant capacity, administration of myricitrin or SLN containing myricitrin improved them. Further, SLN containing myricitrin was more potent than myricitrin.