Melt Emulsification Research Articles

Bone Healing via Carvacrol and Curcumin Nanoparticle on 3D Printed Scaffolds.

Carvacrol is a potent antimicrobial and anti-inflammatory agent, while curcumin possesses antioxidant, anti-inflammatory, and anticancer properties. These phytochemicals have poor solubility, bioavailability, and stability in their free form. Nanoencapsulation can reduce these limitations with enhanced translational capability. Integrating nanocarriers with 3D-printedcalcium phosphate (CaP)scaffolds presents a novel strategy for bone regeneration. Carvacrol and curcumin-loaded nanoparticles (CC-NP) synthesized with melt emulsification produced negatively charged, monodispersed particles with a hydrodynamic diameter of ≈127nm. Their release from the scaffold shows a biphasic release under physiological and acidic conditions. At pH 5.0, the CC-NP exhibits a 53% release of curcumin and nearly 100% release of carvacrol, compared to 19% and 36% from their respective drug solutions. At pH 7.4, ≈40% of curcumin and 76% of carvacrol releases, highlighting their pH-sensitive release mechanism. In vitro studies demonstrate a 1.4-fold increase in osteoblast cell viability with CC-NP treatment. CC-NP exhibit cytotoxic effects against osteosarcoma cells, reducing cell viability by ≈2.9-fold. The antibacterial efficacy of CC-NP evaluated against Staphylococcus aureus (SA) and Pseudomonas aeruginosa (PA) exhibiting 98% antibacterial efficacy. This approach enhances therapeutic outcomes and minimizes the potential side effects associated with conventional treatments, paving the way for innovative applications in regenerative medicine.

Guiding Therapeutics: Lipid Labyrinths and Nanostructures for Enhanced Drug Delivery

Abstract: Nanostructured lipid carriers (NLCs) offer a breakthrough platform for drug therapy, surpassing traditional limitations and delivering exceptional performance. Among various nanoparticulate systems, lipid nanoparticles stand out as one of the most promising options for medication delivery. NLCs stand out due to their solid matrix at ambient temperatures, setting them apart from conventional lipid-based carriers such as nanoemulsions and solid lipid nanoparticles. This paper thoroughly explores the makeup, classification, components, and various methods of preparing NLCs, based on extensive research findings. It emphasizes their numerous advantages, such as improved stability, minimal toxicity, extended storage capability, increased drug-loading capacity, and compatibility with biological systems. The review provides insights into the advantages and limitations of each method. Exploring the intricacies of drug loading and release, the review also addresses strategies to bolster NLCs’ stability. Moreover, it provides a detailed summary of both laboratory- based and animal studies demonstrating the efficacy of NLCs carrying cytotoxic drugs, particularly emphasizing their promise in targeted drug delivery to the brain. As the next-generation lipid nanocarriers, NLCs are composed of physiological and biocompatible lipids, rendering them novel pharmaceutical formulations. These colloidal drug delivery systems boast a solid lipid matrix with nanosized structures, offering superior drug loading capacity, physical stability, and bioavailability compared to conventional lipid nanoparticles. Several techniques, including high-pressure homogenization, microemulsion, solvent evaporation, and melt emulsification, add to the flexibility of nanostructured lipid carriers. Additionally, their exterior can be altered using coatings such as polyethylene glycol, chitosan, or antibodies to improve targeting ability and stealth characteristics. By elucidating the promising role of NLCs across diverse drug delivery systems, this review stimulates interest in their potential applications. It underscores the significance of understanding the structure, content, multiple formulation procedures, and characterization of NLCs, which are pivotal aspects for establishing stable drug delivery systems.

Quality by Design Approach for the Development of Cariprazine Hydrochloride Loaded Lipid-Based Formulation for Brain Delivery via Intranasal Route.

Cariprazine (CPZ) is a third-generation antipsychotic medication that has been approved for treating schizophrenia. This study aimed to develop a cariprazine-loaded nanostructured lipid carrier (CPZ-NLCs) to prevent first-pass metabolism and improve bioavailability and site-specific delivery from the nose to the brain. The CPZ-NLCs were prepared using melt emulsification. The formulation was optimized using the Box-Behnken design (BBD); where the influence of independent variables on critical quality attributes, such as particle size and entrapment efficiency, was studied. The optimized batch (F6) had a particle size of 173.3 ± 0.6 nm and an entrapment efficiency of 96.1 ± 0.57%, respectively. The in vitro release showed >96% release of CPZ from NLC within 30 min. The optimized formulation's ex vivo studies revealed significantly increased CPZ permeability (>75%) in sheep nasal mucosa compared to the CPZ suspension (~26%). The ciliotoxicity study of the nasal mucosa revealed that the CPZ-NLC formulation did not affect the nasal epithelium. The intranasal administration of the formulation achieved 76.14±6.23 μg/ml concentration in the brain which was significantly higher than the oral CPZ suspension administration (30.46±7.24 μg/ml). The developed formulation was stable for 3 months. The study concluded that the developed CPZ-NLC could significantly improve the bioavailability with quick delivery to the brain.

Myristic Acid Solid Lipid Nanoparticles Enhance the Oral Bioavailability and Therapeutic Efficacy of Rifaximin against MRSA Pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is one of the leading causes of death and an immense financial burden on healthcare systems. Rifaximin (RFX) has good antibacterial activity against MRSA, but its clinical application is limited due to its poor oral absorption. Solid lipid nanoparticles have good biocompatibility, high drug loading, sustained release performance, and the inertia of lipids in gastric acid, which facilitates oral drug delivery. In order to improve the oral bioavailability of rifaximin and expand the clinical application of RFX for MRSA pneumonia, this study developed RFX-loaded myristic acid solid lipid nanoparticles (RFX-SLNs). This study first prepared RFX-SLNs through hot melt emulsification and ultrasonic methods and selected the optimal formula of RFX-SLNs through single-factor screening. Afterward, the particle size, zeta potential, and polydispersity index (PDI) of the RFX-SLNs were measured, the morphology of RFX-SLNs was observed by transmission electron microscopy, and the encapsulation efficiency (EE) and drug loading capacity (LC) of RFX-SLNs were detected by high-performance liquid chromatography. Then, the sustained release ability and oral bioavailability of RFX-SLNs were studied through in vitro release and pharmacokinetics. Finally, the therapeutic effect of RFX-SLNs on MRSA pneumonia infection was studied by using a mouse MRSA pneumonia infection model. The optimal formulation of RFX-SLNs was 1% RFX with water (3% PVA) and oil (myristic acid) ratio of 1:19. RFX-SLNs were spherical in shape with a smooth surface and uniform size. The EE and LC of three different batches of RFX-SLNs were 89.35±2.47%, 90.45±3.69%, 88.72±1.18%, and 9.50 ± 0.01%, 10.09±0.01%, and 9.68±0.00%, respectively. In vitro release and pharmacokinetic studies showed that the myristic acid solid lipid nanoparticles showed excellent sustained release as expected and increased the oral bioavailability of RFX by 2.18 times. This indicates that RFX-SLNs can be used for the oral treatment of bacterial infections. Compared to RFX, RFX-SLNs showed good therapeutic effects in a mouse MRSA pneumonia infection model. This study indicates that the myristic acid solid lipid nanoparticles might be an effective way to enhance the oral absorption and therapy effects of RFX and other insoluble drugs. This not only opens up avenues for the clinical application of RFX but also provides a way for the development of new dosage forms of water-soluble drugs and the expansion of their clinical application scope.

Dopamine and Citicoline-Co-Loaded Solid Lipid Nanoparticles as Multifunctional Nanomedicines for Parkinson's Disease Treatment by Intranasal Administration.

This work aimed to evaluate the potential of the nanosystems constituted by dopamine (DA) and the antioxidant Citicoline (CIT) co-loaded in solid lipid nanoparticles (SLNs) for intranasal administration in the treatment of Parkinson disease (PD). Such nanosystems, denoted as DA-CIT-SLNs, were designed according to the concept of multifunctional nanomedicine where multiple biological roles are combined into a single nanocarrier and prepared by the melt emulsification method employing the self-emulsifying Gelucire® 50/13 as lipid matrix. The resulting DA-CIT-SLNs were characterized regarding particle size, surface charge, encapsulation efficiency, morphology, and physical stability. Differential scanning calorimetry, FT-IR, and X ray diffraction studies were carried out to gain information on solid-state features, and in vitro release tests in simulated nasal fluid (SNF) were performed. Monitoring the particle size at two temperatures (4 °C and 37 °C), the size enlargement observed over the time at 37 °C was lower than that observed at 4 °C, even though at higher temperature, color changes occurred, indicative of possible neurotransmitter decomposition. Solid-state studies indicated a reduction in the crystallinity when DA and CIT are co-encapsulated in DA-CIT-SLNs. Interestingly, in vitro release studies in SNF indicated a sustained release of DA. Furthermore, DA-CIT SLNs displayed high cytocompatibility with both human nasal RPMI 2650 and neuronal SH-SY5Y cells. Furthermore, OxyBlot assay demonstrated considerable potential to assess the protective effect of antioxidant agents against oxidative cellular damage. Thus, such protective effect was shown by DA-CIT-SLNs, which constitute a promising formulation for PD application.

Morphological and Structural Characterization of Encapsulated Arginine Systems for Dietary Inclusion in Ruminants

This research evaluated two methods of arginine encapsulation, melt emulsification and nanoprecipitation, using a lipid matrix of carnauba wax and commercial polymers (Eudragit®) as a protective material. The ratios of wax–arginine were 1:1, 2:1, 3:1, and 4:1, while those of Eudragit® RS:RL were 30:70 and 40:60 in proportions of 1:0.5 and 1:1 Eudragit®–arginine. The microcapsules were morphostructurally characterized by scanning electron microscopy, and a microelement analysis was performed via energy-dispersive X-ray spectroscopy and Fourier transform infrared spectroscopy. Additionally, in vitro digestibility was used to determine the protection efficiency. Both encapsulated systems presented regular (crystals) and spherical (microcapsules) polyhedral morphologies. Qualitative nitrogen decreased significantly as the wax ratio increased in the wax–arginine formulations. The formulations with a 1:1 Eudragit:–arginine ratio (1000 mg arginine) produced a higher nitrogen content in the encapsulated systems than the formulations containing 500 mg of arginine. The 2:1 and 3:1 wax–arginine formulations had the lowest degradability after 5 h of rumen fluid exposure (40.7 and 21.26%, respectively) in comparison with 100% unencapsulated arginine. The 3:1 wax–arginine formulation is an efficient encapsulating system which protects against rumen degradation. The more intense absorption bands at 1738 cm−1 and 1468 cm−1 associated with the C=O and C-H groups in carnauba wax indicate that arginine was more protected than in the other systems.

Determination of Chlorogenic Acid in Solid-lipid Nanoparticles: Validation by UV-spectroscopy

Objective: The objective of the research was the development and validation of a simple, sensitive, accurate, robust, and precise UV-spectroscopic method for the quantitative determination of chlorogenic acid loaded in solid-lipid nanoparticles as per the guidelines of the International Conference on Harmonization. Methods: The solid-lipid nanoparticles of chlorogenic acid were prepared using the hot melt emulsification method and the high-speed homogenizer method. Glyceryl monostearate was used as a solid lipid, and Tween 80 was used as a surfactant for the preparation of chlorogenic acid-loaded solid lipid nanoparticles. The method was validated in terms of linearity, accuracy, precision, robustness, ruggedness, limit of detection, and limit of quantification. Results: The chlorogenic acid exhibited absorption maxima at the wavelength of 330 nm. The regression equation from the calibration curve was y=0.006x + 0.0193 with a correlation coefficient of 0.9989. The percentage recovery was found to be 99.92, 99.80, and 99.86, respectively (within the acceptable limit of 98-102%), which validated the accuracy of the method. Furthermore, the method exhibited precision, robustness, and ruggedness, as illustrated by a relative standard deviation (RSD) of less than 2%. The limit of detection and limit of quantification were found to be 6.97 and 21.13 μg/ml, respectively. Conclusion: It was concluded that the proposed spectrophotometer analytical method for the determination of Chlorogenic acid was found reliable, accurate, consistent, precise, accurate, and robust. Therefore, the proposed analytical technique could be an integral part of further evaluation and characterization of Chlorogenic acid-solid lipid nanoparticles.

3D printed scaffolds with quercetin and vitamin D3 nanocarriers: In vitro cellular evaluation.

Increasing bone diseases and anomalies significantly challenge bone regeneration, necessitating the development of innovative implantable devices for effective healing. This study explores the potential of 3D-printed calcium phosphate (CaP) scaffolds functionalized with natural medicine to address this issue. Specifically, quercetin and vitamin D3 (QVD) encapsulated solid lipid nanoparticles (QVD-SLNs) are incorporated into the scaffold to enhance bone regeneration. The melt emulsification method is utilized to achieve high drug encapsulation efficiency (~98%) and controlled biphasic release kinetics. The process-structure-property performance of these systems allows more controlled release while maintaining healthy cell-material interactions. The functionalized scaffolds show ~1.3- and ~-1.6-fold increase in osteoblast cell proliferation and differentiation, respectively, as compared with the control. The treated scaffold demonstrates a reduction in osteoclastic activity as compared with the control. The QVD-SLN-loaded scaffolds show ~4.2-fold in vitro chemopreventive potential against osteosarcoma cells. Bacterial assessment with both Staphylococcus aureus and Pseudomonas aeruginosa shows a significant reduction in bacterial colony growth over the treated scaffold. These findings summarize that the release of QVD-SLNs through a 3D-printed CaP scaffold can treat various bone-related disorders for low or non-load-bearing applications.

The Evolution of Nanocrystalline Drug Delivery System

Developing nanocrystalline drug delivery technologies is a noteworthy advancement in pharmaceutical science. The nanocrystalline formulations aim to improve therapeutic efficacy, pharmaceutical solubility, and bioavailability. We develop many methods for their fabrication, with top-down, bottom-up, and combination procedures, beginning with reasoning behind nanocrystalline approaches. In this type of review, we focused on the progress of nanocrystalline drug delivery systems in various years by applying different techniques which started in 1990 and what dosage forms are still made by this technology. It is found that various other techniques are also there manufacturing of drug Nanocrystals through years of investigation made by specialists. The researchers found methods such as Top-down, bottom-up, combination, solvent displacement technology, fluidised bed technology, freeze drying, spray drying, electrodynamic technique, and melt emulsification. Every process has advantages and disadvantages, therefore selecting the proper technology is critical to produce drug nanocrystals successfully. Keywords: Nanocrysyals, CT, Bottom-up, Top-Down, HPH, Nanocarriers

Evaluation of preclinical efficacy of apremilast-loaded liquid crystalline nanoparticulate gel in amelioration of atopic dermatitis

Apremilast is a phosphodiesterase-4 inhibitor currently under investigation for managing atopic dermatitis, but it is associated with poor physicochemical properties, majorly affecting its bioavailability. To improve the topical delivery, we have encapsulated apremilast into the liquid crystalline nanoparticles and evaluated its preclinical efficacy against atopic dermatitis. The liquid crystalline nanoparticles were manufactured by the melt emulsification method followed by probe sonication. The prepared nanoparticles were evaluated for particle size, zeta potential, encapsulation efficiency and in vitro release. Further, the apremilast liquid crystalline nanoparticles were loaded into the gel base by magnetic stirring. The gel formulation was evaluated for viscosity, textural profile, drug content, ex vivo permeation, and retention in mice skin. The preclinical efficacy of optimized gel formulation was assessed in 2,4-dinitrochlorobenzene induced atopic dermatitis in mice model followed by histopathological examination of skin sections. The apremilast was successfully loaded into the liquid crystalline nanoparticles with an average particle size of 180 ± 0.45 nm and entrapment efficiency of 89.42 ± 4.27 %. The optimized nanoparticles were successfully loaded into gel base showing pseudoplastic shear thinning behaviour. In vivo preclinical efficacy of the optimized gel formulation revealed improved skin structure in comparison with negative control group. The histopathological examination of mice skin treated with optimized gel formulation resulted in decreased epidermal hyperplasia and intactness of outer keratinized epidermal layer with the inner layer. The outcomes of the apremilast-loaded liquid crystalline nanoparticulate gel demonstrated anti-atopic dermatitis potential.

Development of solid lipid microparticles (SLMs) containing asiatic acid for topical treatment of acne: Characterization, stability, in vitro and in vivo anti-acne assessment

Solid lipid microparticles (SLMs) represent a promising approach for drug delivery in anti-acne applications. In this study, asiatic acid-loaded SLMs (AASLMs) were prepared by melt emulsification method in conjunction with freeze-drying. Comprehensive evaluations comprised particle size, %entrapment efficiency (%EE), %labeled amount (%LA), surface morphology, stability, %release, %skin permeation, and anti-acne activity. The AASLMs exhibited an average particle size ranging from 7.46 to 38.86 µm, with %EE and %LA falling within the range of 31.56 to 100.00 and 90.43 to 95.38, respectively. The AASLMs demonstrated a spherical shape under scanning electron microscopy, and maintained stability over a 3-month period. Notably, formulations with 10 % and 15 % cetyl alcohol stabilized with poloxamer-188 (specifically F6 and F12) displayed a minimum inhibitory concentration (MIC) value of 75 mg/ml against Cutibacterium acnes. Furthermore, F12 exhibited a higher %release and %skin permeation compared to F6 over 24 h. In a single-blind clinical trial involving fifteen participants with mild-to-moderate acne, F12 showcased its potential not only in reducing porphyrin intensity and enhancing skin barriers but also in significantly improving skin hydration and brightness. However, further investigations with larger subject cohorts encompassing diverse age groups and genders are necessary to thoroughly establish the performance of the developed AASLMs.

Topical co-delivery of tacrolimus and calcipotriol loaded nanostructured lipid carrier: a potential and synergistic approach in the management of psoriasis

The focus of this study was to develop a Vitamin-D3 (Calcipotriol)-based Tacrolimus (TAC)-loaded nanostructured lipid carrier (NLC) for topical application to treat psoriasis. The sonication technique followed by melt emulsification was used to formulate TAC-NLC, in which Precirol ATO-5, Calcipotriol, and Solutol HS-15 were used as excipients. Based on the analysis of particle size, PDI, and entrapment efficiency of various TAC-NLCs using Box-Behnken Design, an optimized NLC was selected. The selected nanocarrier was further transformed into the gel and then characterized for in vitro release, in vitro and ex vivo permeation, and dermatokinetic, including in vitro characterization studies. The optimized TAC-NLC had a particle size of 231 ± 1.52 nm with a narrow PDI of 0.40 ± 0.001 along with high entrapment efficiency (84.04 ± 1.36%) and drug loading (12.61 ± 0.20%)”. The in vitro release showed sustained release throughout 12 h. Moreover, dissimilarity (f1:52) and the similarity factor (f2:37) showed a lack of any similarity in the evaluation of drug release from TAC-NLC formulation and Conventional formulation. The time requisite to release 50% (T50), 30% (T30), and 20% (T20) of the drug is also calculated. The flux and permeability coefficients were found to be 11.59 µg/cm2/h and 0.0386 cm/h. A dermatokinetic study of TAC-NLC indicated a remarkable rise in AUC0-12h and CSkin max compared to conventional formulation (p < 0.005). Further, the vitro studies indicated higher cell viability (85%-80%) on melanoma cells than aqueous suspension of the drug (60–70%). The study indicated that the topical application of TAC-NLC nanogel was found potentially useful for the management of psoriasis.

Design Optimization and Evaluation of Solid Lipid Nanoparticles of Azelnidipine for the treatment of Hypertension.

Solid lipid nanoparticles (SLN) are the most promising lipid-based drug delivery utilized for enhancing the solubility, bioavailability, and therapeutic efficacy of poorly water-soluble molecules. Azelnidipine (AZN) is a calcium channel blocker widely recommended for the treatment of high blood pressure but its activity is restricted due to high lipophilicity and poor solubility in the GIT. The current research focused on the development of the SLN of AZN and thereby improving the absorption, bioavailability, and therapeutic efficacy in hypertension which is a leading cause of death worldwide. Recent patents on SLN was available as U.S. Patent,10,973,798B2, U.S. Patent 10,251,960B2, U.S. Patent 2021/0069121A1, U.S. Patent 2022/0151945A1. SLN was developed by hot melt emulsification and ultrasonication method using glyceryl monostearate (GMS) as solid lipid and Poloxamer 188 as a surfactant for the stabilization of colloidal dispersion. Box-Behnken model was utilized which predicted 13 batches in which concentration of GMS (X1), Poloxamer 188 (X2) and sonication time (X3) were considered as independent parameters. The particle size (Y1) and entrapment efficiency (Y2) were dependable parameters and optimized batch F2 showed a particle size of 166.4 nm, polydispersity index of 0.40 and zeta potential of -13.7 mV. The entrapment efficiency was observed at 86.21 %. FTIR spectra confirm the identity and compatibility with the formulation components. The differential scanning calorimetry (DSC) confirmed the absence of melting point and interpreted that AZN was entirely incorporated in the lipid matrix and transformed from crystalline to amorphous form. The ANOVA for the particle size (p-value: 0.0203), % EE (p-value: 0.0271) was found significant. The in-vitro drug release showed a sustained release pattern for about 12 h. The AZN-loaded SLN was lyophilized and intended for oral delivery. AZN-loaded SLN was developed by the hot melt emulsification method which accelerated the solubility and bioavailability and released in a sustained manner for treating hypertension.

Enhancing safety through the biodegradable pesticide microcapsules produced via melt emulsification and interfacial polymerization

Pesticides play a crucial role in securing food production, their safety usage remains a pressing concern. Traditional pesticide formulations have been scrutinized for their inefficiency, environmental hazards, and negative impacts on human health. Here, sulfonated cellulose nanocrystals (sCNC) were utilized to stabilize molten lambda-cyhalothrin (LC), forming stable Pickering emulsions via high-pressure homogenization (HPH). This process was followed by the generation of microcapsules through interfacial polymerization, a method that entirely forgoes the use of surfactants and organic solvents. The synthesized microcapsules showcased a size ranging from 250 to 1000 nm, with an impressive LC encapsulation efficiency of up to 99.29 %. These microcapsules maintained excellent stability, prolonging pest control duration in field applications, and exhibited reduced toxicity to zebrafish. A particularly groundbreaking discovery was the ability of microcapsules to mitigate skin irritation, a benefit previously unexplored in LC microencapsulation. Furthermore, these microcapsules demonstrated significant degradation within 14 days post-application, effectively minimizing prolonged pesticide residue on crops. This study highlights the eco-friendly production of microcapsules and their capacity to diminish the negative impacts associated with pesticide application. It paves the way for the wider implementation of encapsulation technologies in pesticides and offers critical insights into the creation of sustainable, safe, and effective pesticide formulations.

Characterization and stability assessment of Ocimum gratissimum leaves extract loaded nanostructured lipid carrier

AbstractIn the last few decades, several nanoparticles technologies of actives delivery systems have emerged in the formulation of personal care products. The purpose of this study is to formulate the nanostructured lipid carrier loaded with Ocimum gratissimum leaves extract (OGNLC) and to characterize the chemical and physical properties of the OGNLC formulation. Ultrasound‐Assisted Extraction (UAE) method are used in this study to obtain O. gratissimum extract with the determination of the TPC, while melt emulsification homogenization conjoined with ultrasonic homogenization method are used to prepare OGNLC samples. Two types of surfactants (Tween 80 and soy lecithin) are incorporated in the formulation to form OGNLC with various compositions (%) to determine the best formulation. The effect of varying compositions of surfactants in OGNLC samples on the mean particle size (MPS), polydispersity index (PDI), zeta potential (ZP) and encapsulation efficiency (EE%) of OGNLC are characterized. The best formulation also was analyzed by FTIR spectroscopy, and the encapsulation efficiency are determined. The stability of OGNLC particle size was also assessed after 30 days of exposure under low and room temperature (4°C, 25°C). An optimal OGNLC consists of 2.0% O. gratissimum extract, 2.0% GMS, 10.0% VCO, and varying surfactant compositions of 2.0% of Tween 80, and 1.0% of soy lecithin by a mean particle size of 155.73 ± 1.53 nm, a PDI value of 0.203 ± 0.007, zeta potential of |−37.2| ± 0.95 mV, and encapsulation efficiency (%) of 95.70% ± 6.256%. The stability assessment of OGNLC showed that the obtained formulation is at least stable for more than 30 days. This study concludes that the composition of surfactants are important factors affecting the size and stability of the OGNLC. This is the first study to report on the synthesis of nanostructured lipid carrier loaded with O. gratissimum.

Formulation, Optimization and In-vitro Evaluation of Chitosan-lipid nanoparticles for Antibacterial activity against Salmonella typhimurium

Salmonella infections are difficult to treat due to the poor permeability of antibiotics into intracellular compartments and the cell walls of microorganisms with less selectivity, which results in the development of drug resistance. Chitosan is a biocompatible, naturally occurring polymer with shown antibacterial activity against a wide range of pathogenic microorganisms. In the present work, chitosan-based polymer lipid nanoparticles (PLNs) were designed to enhance the antibacterial activity against Salmonella typhimurium. PLNs were optimized by 32 full factorial design with two independent variables viz., polymer-lipid ratio (X1) ranging from 0.8 to 1.2 and surfactants (X2) Tween80:Poloxamer188 (2:1) with a concentration of 1% to 2%. Formulations were prepared by melt emulsification with a homogenization process. The influence of independent variables was checked on particle size (Y1), Polydispersity Index (Y2) and Zeta potential (Y3). The optimized batch had particle size of 234.3±4.2nm, a PDI of 0.291±0.01, and a Zeta potential of 28.9±3.4mV. FTIR analysis reveals the polymer's compatibility with lipid and additives. Analysis of DSC and XRD confirmed the existence of amorphous PLNs. The FESEM findings suggest that PLNs have a nearly spherical shape with a smooth surface morphology. Furthermore, the formulation was tested for in-vitro antibacterial activity against Salmonella typhimurium. From the results of an antibacterial study, it was found that the zone of inhibition, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PLNs were 24mm, 15.12µg/ml, and 31.25µg/ml, respectively, which was better than the results of pure chitosan (18mm, 62.5µg/ml, and 125µg/ml).

Development, optimization and in vitro-in vivo evaluation of solid lipid microparticles for improved pharmacokinetic profile of bisoprolol

The current research aimed at designing and optimizing controlled release solid lipid microparticles (SLMs) of Bisoprolol (BPL) from biocompatible waxes by using Box-Bhenken design (BBD) for improving the drug pharmacokinetics, enhancing compliance in hypertensive patients as well as eliminating inefficiencies of traditional methods of drug delivery. Seventeen formulations (F1 to F17) of controlled release BPL loaded SLMs were made by melt emulsification technique where Carnauba wax (CW) and Ceresin wax (CSW) were used as carriers and Tween 80 was used as stabilizer. The SLMs were characterized using fourier transforms infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Results revealed that micromeritics properties of all SLMs were satisfactory and showed good percentage yield (PY) and entrapment efficiency (EE). The minimum EE was observed by formulation-1 (F1) as 21.66% whereas F3 has showed maximum EE as 88%. Results of in vitro release study revealed that all formulations showed a well-controlled release in simulated intestinal medium at pH 7.4. The formulation F3 with high wax concentration revealed best extended release characteristics (29%) in 12 h. The pharmacokinetics studies of SLMs demonstrated an expressively lower Cmax (maximum plasma concentration) of BPL (53.61 ± 2:52) with a satisfactorily higher time to achieve maximum plasma concentration (Tmax) of 10.24 h as compared to Cmax (79.63 ± 5.75) and Tmax (2.45 ± 3.83) of BPL released from commercial brands. Moreover the attainment of greater bioavailability of BPL was most probably due to the increase in half-life (20.44 ± 2.82), mean residence time (24.81 ± 4.22) and area under the plasma concentration level curve (AUC0–24) of 9688.6 ± 4.18 for BPL released from SLMs. Convincingly, the inventive technique could not only sustain the drug release in the in vitro and in vivo environment but also maintain the plasma drug concentration level constant for a longer time without elevating Cmax.

Etoricoxib nanostructured lipid carriers attenuate inflammation by modulating Cyclooxygenase-2 signaling and activation of nuclear factor-κB-p65 pathways in radiation-induced acute cardiotoxicity in rats

The current investigation aimed to explore the potential of etoricoxib nanostructured lipid carriers (ET-NLCs) as an anti-inflammatory drug in radiation-exposed rats, with a focus on assessing its efficacy in reducing inflammation while minimizing cardiac toxicity compared to conventional etoricoxib (ET) treatment. The ET-NLCs were prepared by the low-temperature melt emulsification solidification technique. Various techniques were employed to characterize the NLCs. Rats were exposed to gamma-irradiation (6 Gy) to induce cardiac inflammation and injury, followed by oral administration of ET or ET-NLCs (10 mg/kg b.w.) for 14 consecutive days. Results demonstrated a significant increase in the levels of malondialdehyde (MDA), cyclooxygenase-2 (COX-2), nuclear factor kappa-B p65 (NF-κB-p65), and poly ADP-ribose polymerase (PARP-1) in the heart tissues of gamma-irradiated rats compared to the control group. This increase was accompanied by a reduction in the activity of antioxidant enzymes. However, treatment with ET and ET-NLCs exhibited a positive impact on these levels. Interestingly, the efficacy of ET-NLCs in mitigating radiation-induced inflammation in heart tissue was found to be superior to that of ET. In conclusion, the study suggests that the utilization of NLCs as a drug delivery system for ET may not only enhance its therapeutic efficacy but also help reduce the cardiovascular risks associated with ET, specifically focused on individuals who had been exposed to gamma radiation. These findings open new avenues for further research in the development of effective and safer therapeutic strategies for managing inflammatory diseases and their impact on cardiovascular health.

Nanosuspension: A Novel Approach to Improve the Solubility, Bioavailability and Pharmacokinetics of Poorly Soluble Drugs

Solubility is an essential factor for drug effectiveness, independent of the route of administration. Poorly water soluble drugs show major problems for drug formulation. Many conventional methods exist to address the issues of poor solubility and bioavailability, but they have many drawbacks. Nanotechnology is employed to address the issues related to these traditional methods for improving solubility and bioavailability. Pharmaceutical nanosuspension is a very finely colloid, biphasic, dispersed, solid drug particles in an aqueous vehicle, size below 1µm, without any matrix material, stabilised by surfactants and polymers, prepared by suitable methods for Drug Delivery applications, through various routes of administration such as oral, topical, parenteral, ocular and pulmonary routes. This article covers the advantages, disadvantages, properties, preparation of nanosuspension by bottom up technology, top down technology, melt emulsification, emulsification- solvent evaporation and supercritical fluid with their advantages and disadvantages, evaluation, and their drug delivery applications.

Development of Atomoxetine-Loaded NLC In Situ Gel for Nose-to-Brain Delivery: Optimization, In Vitro, and Preclinical Evaluation.

The present study investigates the brain-targeted efficiency of atomoxetine (AXT)-loaded nanostructured lipid carrier (NLC)-laden thermosensitive in situ gel after intranasal administration. AXT-NLC was prepared by the melt emulsification ultrasonication method and optimized using the Box-Behnken design (BBD). The optimized formulation (AXT-NLC) exhibited particle size PDI, zeta potential, and entrapment efficiency (EE) of 108 nm, 0.271, -42.3 mV, and 84.12%, respectively. The morphology of AXT-NLC was found to be spherical, as confirmed by SEM analysis. DSC results displayed that the AXT was encapsulated within the NLC matrix. Further, optimized NLC (AXT-NLC13) was incorporated into a thermosensitive in situ gel using poloxamer 407 and carbopol gelling agent and evaluated for different parameters. The optimized in situ gel (AXT-NLC13G4) formulation showed excellent viscosity (2532 ± 18 Cps) at 37 °C and formed the gel at 28-34 °C. AXT-NLC13-G4 showed a sustained release of AXT (92.89 ± 3.98% in 12 h) compared to pure AXT (95.47 ± 2.76% in 4 h). The permeation flux through goat nasal mucosa of AXT from pure AXT and AXT-NLC13-G4 was 504.37 µg/cm2·h and 232.41 µg/cm2·h, respectively. AXT-NLC13-G4 intranasally displayed significantly higher absolute bioavailability of AXT (1.59-fold higher) than intravenous administration. AXT-NLC13-G4 intranasally showed 51.91% higher BTP than pure AXT (28.64%) when administered via the same route (intranasally). AXT-NLC13-G4 showed significantly higher BTE (207.92%) than pure AXT (140.14%) when administered intranasally, confirming that a high amount of the AXT reached the brain. With the disrupted performance induced by L-methionine, the AXT-NLC13-G4 showed significantly (p < 0.05) better activity than pure AXT as well as donepezil (standard). The finding concluded that NLC in situ gel is a novel carrier of AXT for improvement of brain delivery by the intranasal route and requires further investigation for more justification.