Chemo-photothermal therapy of chitosan/gold nanorod clusters for antibacterial treatment against the infection of planktonic and biofilm MRSA.

Bacterial infections trigger inflammation and impede the closure of skin wounds. The misuse of antibiotics exacerbates skin infections by generating multidrug-resistant bacteria. In this study, we developed chemo-photothermal therapy (chemo-PTT) based on near-infrared (NIR)-irradiated chitosan/gold nanorod (GNR) clusters as anti-methicillin-resistant Staphylococcus aureus (MRSA) agents. The nanocomposites exhibited an average size of 223 nm with a surface charge of 36 mV. These plasmonic nanocomposites demonstrated on-demand and rapid hyperthermal action under NIR. The combined effect of positive charge and PTT by NIR-irradiated nanocomposites resulted in a remarkable inhibition rate of 96 % against planktonic MRSA, indicating a synergistic activity compared to chitosan nanoparticles or GNR alone. The nanocomposites easily penetrated the biofilm matrix. The combination of chemical and photothermal treatments by NIR-stimulated clusters significantly damaged the biofilm structure, eradicating MRSA inside the biomass. NIR-irradiated chitosan/GNR clusters increased the skin temperature of mice by 13 °C. The plasmonic nanocomposites induced negligible skin irritation in vivo. In summary, this novel nanosystem demonstrated potent antibacterial effects against planktonic and biofilm MRSA, showcasing the possible efficacy in treating skin infections.

Facile adipocyte uptake and liver/adipose tissue delivery of conjugated linoleic acid-loaded tocol nanocarriers for a synergistic anti-adipogenesis effect.

Obesity is a major risk to human health. Adipogenesis is blocked by α-tocopherol and conjugated linoleic acid (CLA). However, their effect at preventing obesity is uncertain. The effectiveness of the bioactive agents is associated with their delivery method. Herein, we designed CLA-loaded tocol nanostructured lipid carriers (NLCs) for enhancing the anti-adipogenic activity of α-tocopherol and CLA. Adipogenesis inhibition by the nanocarriers was examined using an in vitro adipocyte model and an in vivo rat model fed a high fat diet (HFD). The targeting of the tocol NLCs into adipocytes and adipose tissues were also investigated. A synergistic anti-adipogenesis effect was observed for the combination of free α-tocopherol and CLA. Nanoparticles with different amounts of solid lipid were developed with an average size of 121‒151 nm. The NLCs with the smallest size (121 nm) showed greater adipocyte internalization and differentiation prevention than the larger size. The small-sized NLCs promoted CLA delivery into adipocytes by 5.5-fold as compared to free control. The nanocarriers reduced fat accumulation in adipocytes by counteracting the expression of the adipogenic transcription factors peroxisome proliferator activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α, and lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Localized administration of CLA-loaded tocol NLCs significantly reduced body weight, total cholesterol, and liver damage indicators in obese rats. The biodistribution study demonstrated that the nanoparticles mainly accumulated in liver and adipose tissues. The NLCs decreased adipocyte hypertrophy and cytokine overexpression in the groin and epididymis to a greater degree than the combination of free α-tocopherol and CLA. In conclusion, the lipid-based nanocarriers were verified to inhibit adipogenesis in an efficient and safe way.

Skin delivery of synthetic benzoyl pterostilbenes suppresses atopic dermatitis-like inflammation through the inhibition of keratinocyte and macrophage activation.

Atopic dermatitis (AD) is one of the most common skin autoimmune diseases needing continuous anti-inflammatory management. Pterostilbene is reported to exhibit anti-inflammatory activity with higher bioavailability and stability than its parent compound, resveratrol. In this study, a series of synthetic pterostilbene analogs were designed by the hybridization of pterostilbene with chalcones or benzoyl chloride. Seventeen analogs derived from pterostilbene were synthesized with differences in the positions of hydroxyl, methoxyl, or fluoro moieties. These compounds were screened by the inhibitory effect on the overexpressed Th2-associated cytokines/chemokines in the activated human keratinocytes (HaCaT). The anti-IL-5 and anti-CCL5 activity of these compounds led to the identification of three effective compounds: 3a ((E)- 4-(3,5-dimethoxystyryl)phenyl benzoate), 3d ((E)- 4-(3,5-dimethoxystyryl)phenyl 2-methoxybenzoate), and 3g ((E)- 4-(3,5-dimethoxystyryl)phenyl 2-fluorobenzoate). These benzoyl pterostilbenes also significantly decreased Th1/Th17-associated proinflammatory mediators in the activated macrophages (differentiated THP-1). The result showed that the conditioned medium of benzoyl pterostilbene-treated macrophages reduced the phosphorylated STAT3 in the keratinocytes, indicating the blockade of crosstalk between resident and immune cells. Compounds 3d and 3g generally showed greater skin absorption than 3a. The flux of 3g across barrier-defective skins mimicking the AD skin was 3-fold higher than that of across intact skin. The dinitrochlorobenzene (DNCB)-induced AD mouse model manifested that topical delivery with 3g improved the pathological signs through inhibiting cytokines/chemokines (IL-5, TNF-α, CCL17, and CCL22) and macrophage recruitment. The epidermal thickness was reduced from 76 to 55 µm after topical 3g delivery. The therapeutic activity of 3g was comparable to that of tacrolimus (TAC) used as a positive control. The benzoyl pterostilbenes attenuated the inflammation via the MAPK and c-Jun signaling. Furthermore, this study provided experimental evidence of benzoyl pterostilbene analogs for therapeutic potential on AD.

Enhanced Apigenin Dissolution and Effectiveness Using Glycyrrhizin Spray-Dried Solid Dispersions Filled in 3D-Printed Tablets.

This study aimed to prepare glycyrrhizin-apigenin spray-dried solid dispersions and develop PVA filament-based 3D printlets to enhance the dissolution and therapeutic effects of apigenin (APN); three formulations (APN1-APN3) were proportioned from 1:1 to 1:3. A physicochemical analysis was conducted, which revealed process yields of 80.5-91% and APN content within 98.0-102.0%. FTIR spectroscopy confirmed the structural preservation of APN, while Powder-XRD analysis and Differential Scanning Calorimetry indicated its transformation from a crystalline to an amorphous form. APN2 exhibited improved flow properties, a lower Angle of Repose, and Carr's Index, enhancing compressibility, with the Hausner Ratio confirming favorable flow properties for pharmaceutical applications. In vitro dissolution studies demonstrated superior performance with APN2, releasing up to 94.65% of the drug and revealing controlled release mechanisms with a lower mean dissolution time of 71.80 min and a higher dissolution efficiency of 19.2% compared to the marketed APN formulation. This signified enhanced dissolution and improved therapeutic onset. APN2 exhibited enhanced antioxidant activity; superior cytotoxicity against colon cancer cells (HCT-116), with a lower IC50 than APN pure; and increased antimicrobial activity. A stability study confirmed the consistency of APN2 after 90 days, as per ICH, with an f2 value of 70.59 for both test and reference formulations, ensuring reliable pharmaceutical development. This research underscores the potential of glycyrrhizin-apigenin solid dispersions for pharmaceutical and therapeutic applications, particularly highlighting the superior physicochemical properties, dissolution behavior, biological activities, and stability of APN2, while the development of a 3D printlet shell offers promise for enhanced drug delivery and therapeutic outcomes in colon cancer treatment, displaying advanced formulation and processing techniques.

Development of Gefitinib-Loaded Solid Lipid Nanoparticles for the Treatment of Breast Cancer: Physicochemical Evaluation, Stability, and Anticancer Activity in Breast Cancer (MCF-7) Cells.

In the current study, the toxic effects of gefitinib-loaded solid lipid nanoparticles (GFT-loaded SLNs) upon human breast cancer cell lines (MCF-7) were investigated. GFT-loaded SLNs were prepared through a single emulsification-evaporation technique using glyceryl tristearate (Dynasan™ 114) along with lipoid® 90H (lipid surfactant) and Kolliphore® 188 (water-soluble surfactant). Four formulae were developed by varying the weight of the lipoid™ 90H (100-250 mg), and the GFT-loaded SLN (F4) formulation was optimized in terms of particle size (472 ± 7.5 nm), PDI (0.249), ZP (-15.2 ± 2.3), and EE (83.18 ± 4.7%). The optimized formulation was further subjected for in vitro release, stability studies, and MTT assay against MCF-7 cell lines. GFT from SLNs exhibited sustained release of the drug for 48 h, and release kinetics followed the Korsmeyer-Peppas model, which indicates the mechanism of drug release by swelling and/or erosion from a lipid matrix. When pure GFT and GFT-SLNs were exposed to MCF-7 cells, the activities of p53 (3.4 and 3.7 times), caspase-3 (5.61 and 7.7 times), and caspase-9 (1.48 and 1.69 times) were enhanced, respectively, over those in control cells. The results suggest that GFT-loaded SLNs (F4) may represent a promising therapeutic alternative for breast cancer.

Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica.

Designing a robust direct compression (DC) formulation for an active pharmaceutical ingredient (API) with poor flow and compaction properties at a high API load is challenging. This study tackled two challenges: the unfavorable flow characteristics and tableting problems associated with a high-drug-loading canagliflozin (CNG), facilitating high-speed DC tableting. This was accomplished through a single-step dry coating process using hydrophilic nano-sized colloidal silica. A 32 full-factorial experimental design was carried out to optimize the independent process variables, namely, the weight percent of silica nanoparticles (X1) and mixing time (X2). Flow, bulk density, and compaction properties of CNG-silica blends were investigated, and the optimized blend was subsequently compressed into tablets using the DC technique. A regression analysis exhibited a significant (p ≤ 0.05) influence of both X1 and X2 on the characteristics of CNG with a predominant effect of X1. Additionally, robust tablets were produced from the processed powders in comparison with those from the control batch. Furthermore, the produced tablets showed significantly lower tablet ejection forces than those from the control batch, highlighting the lubrication impact of the silica nanoparticles. Interestingly, these tablets displayed improved disintegration time and dissolution rates. In conclusion, a dry coating process using silica nanoparticles presents a chance to address the poor flow and tableting problems of CNG, while minimizing the need for excessive excipients, which is crucial for the effective development of a small-sized tablet and the achievement of a cost-effective manufacturing process.

Small interfering RNA-based nanotherapeutics for treating skin-related diseases.

INTRODUCTION: RNA interference (RNAi) has demonstrated great potential in treating skin-related diseases, as small interfering RNA (siRNA) can efficiently silence specific genes. The design of skin delivery systems for siRNA is important to protect the nucleic acid while facilitating both skin targeting and cellular ingestion. Entrapment of siRNA into nanocarriers can accomplish these aims, contributing to improved targeting, controlled release, and increased transfection. AREAS COVERED: The siRNA-based nanotherapeutics for treating skin disorders are summarized. First, the mechanisms of RNAi are presented, followed by the introduction of challenges for skin therapy. Then, the different nanoparticle types used for siRNA skin delivery are described. Subsequently, we introduce the mechanisms of how nanoparticles enhance siRNA skin penetration. Finally, the current investigations associated with nanoparticulate siRNA application in skin disease management are reviewed. EXPERT OPINION: The potential application of nanotherapeutic RNAi allows for a novel skin application strategy. Further clinical studies are required to confirm the findings in the cell-based or animal experiments. The capability of large-scale production and reproducibility of nanoparticle products are also critical for translation to commercialization. siRNA delivery by nanocarriers should be optimized to attain cutaneous targeting without the risk of toxicity.

Development and Optimization of Sildenafil Orodispersible Mini-Tablets (ODMTs) for Treatment of Pediatric Pulmonary Hypertension Using Response Surface Methodology.

The availability of age-appropriate oral dosage forms for pediatric patients has remained a challenge. Orodispersible mini-tablets (ODMTs) are a promising delivery system for pediatric patients. The purpose of this work was the development and optimization of sildenafil ODMTs as a new dosage form for the treatment of pulmonary hypertension in children using a design-of-experiment (DoE) approach. A two-factor, three levels (32) full-factorial design was employed to obtain the optimized formulation. The levels of microcrystalline cellulose (MCC; 10-40% w/w) and partially pre-gelatinized starch (PPGS; 2-10% w/w) were set as independent formulation variables. In addition, mechanical strength, disintegration time (DT), and percent drug release were set as critical quality attributes (CQAs) of sildenafil ODMTs. Further, formulation variables were optimized using the desirability function. ANOVA analysis proved that MCC and PPGS had a significant (p < 0.05) impact on CQAs of sildenafil ODMTs with a pronounced influence of PPGS. The optimized formulation was achieved at low (10% w/w) and high (10% w/w) levels of MCC and PPGS, respectively. The optimized sildenafil ODMTs showed crushing strength of 4.72 ± 0.34 KP, friability of 0.71 ± 0.04%, DT of 39.11 ± 1.03 s, and sildenafil release of 86.21 ± 2.41% after 30 min that achieves the USP acceptance criteria for ODMTs. Validation experiments have shown that the acceptable prediction error (<5%) indicated the robustness of the generated design. In conclusion, sildenafil ODMTs have been developed as a suitable oral formulation for the treatment of pediatric pulmonary hypertension using the fluid bed granulation process and the DoE approach.

TiO2-embedded mesoporous silica with lower porosity is beneficial to adsorb the pollutants and retard UV filter absorption: A possible application for outdoor skin protection.

The purpose of the current investigation was to develop multifunctional TiO2-embedded mesoporous silica incorporating avobenzone to protect against environmental stress through pollutant adsorption and UVA protection. We sought to explore the effect of the mesoporous porosity on the capability of contaminant capture and the suppression of avobenzone skin penetration. The porosity of the mesoporous silica was tuned by adjusting the ratio of template triblock copolymers (Pluronic P123 and F68). The Pluronic P123:F68 ratios of 3:1, 2:2, and 1:3 produced mesoporous silica with pore volumes of 0.66 (TiO2/SBA-L), 0.47 (TiO2/SBA-M), and 0.25 (TiO2/SBA-S) cm3/g, respectively. X-ray scattering and electron microscopy confirmed the SBA-15 structure of the as-prepared material had a size of 3-5 µm. The maximum adsorbability of fluoranthene and methylene blue was found to be 43% and 53% for the TiO2/SBA-S under UVA light, respectively. The avobenzone loaded into the mesoporous silica demonstrated the synergistic effect of in vitro UVA protection, reaching an UVA/UVB absorbance ratio of near 1.5 (Boots star rating = 5). The encapsulation of avobenzone into the TiO2/SBA-S lessened cutaneous avobenzone absorption from 0.76 to 0.50 nmol/mg, whereas no reduction was detected for the TiO2/SBA-L. The avobenzone-loaded TiO2/SBA-S hydrogel exhibited a greater improvement in skin barrier recovery and proinflammatory mediator mitigation compared to the SBA-S hydrogel (without TiO2). The cytokines/chemokines in the photoaged skin were reduced by two- to three-fold after TiO2/SBA-S treatment compared to the non-treatment control. Our data suggested that the mesoporous formulation with low porosity and a specific surface area showed effective adsorbability and UVA protection, with reduced UVA filter absorption. The versatility of the developed mesoporous system indicated a promising potential for outdoor skin protection.

Targeting anti-inflammatory immunonanocarriers to human and murine neutrophils via the Ly6 antigen for psoriasiform dermatitis alleviation.

Psoriasis is a refractory and difficult-to-treat skin disorder. The neutrophil-targeting approach represents a promising option for psoriasis therapy. This study developed and examined NIMP-R14-conjugated immunonanoparticles for specific targeting to neutrophils associated with psoriasiform dermatitis. In the process, roflumilast (RFL), as a phosphodiesterase (PDE) 4 inhibitor, was encapsulated in the nanocarriers to assess the anti-inflammatory capability against primary neutrophil activation and murine psoriasiform lesion. The average size and surface charge of the immunonanocarriers were 305 ± 36 nm and -18 ± 6 mV, respectively. The monovalent antibody-conjugated nanoparticles offered precise uptake by both human and mouse neutrophils but failed to exhibit this effect in monocytes and lymphocytes. The intracellular RFL concentration of the immunonanocarriers was five-fold superior to that of the passive counterparts. The immunonanocarriers specifically recognized the neutrophils through the Ly6 antigen with no apparent cytotoxicity. The antibody-conjugated nanoparticles mitigated superoxide anion production and migration of the activated human neutrophils. The in vivo biodistribution in the psoriasiform mice, found using an in vivo imaging system (IVIS) and liquid chromatography (LC)-mass-mass analysis, showed that the antibody conjugation increased the nanoparticle residence in systemic circulation after intravenous administration. On the other hand, most of the nanoparticles were accumulated in the lesional skin after subcutaneous injection. The actively-targeted nanocarriers were better than the free RFL and unfunctionalized nanoparticles in suppressing psoriasiform inflammation. The immunonanocarriers reduced neutrophil recruitment and epidermal hyperplasia in the plaque. Intravenous and subcutaneous treatments with the immunonanocarriers significantly reduced the overexpressed cytokines and chemokines in the inflamed skin, demonstrating that the nanosystems could both systematically and locally alleviate inflammation. The results indicated that the NIMP-R14-conjugated RFL-loaded nanoparticles have potential as an anti-autoimmune disease delivery system for neutrophil targeting.

Laser-assisted nanoparticle delivery to promote skin absorption and penetration depth of retinoic acid with the aim for treating photoaging.

Retinoic acid (RA) is an approved treatment for skin photoaging induced by ultraviolet (UVA). Topically applied RA is mainly located in the stratum corneum (SC) with limited diffusion into the deeper strata. A delivery system capable of facilitating dermal delivery and cellular internalization for RA is critical for a successful photoaging therapy. Two delivery approaches, namely nanoparticles and laser ablation, were combined to improve RA's absorption efficacy and safety. The nanoparticle absorption enhancement by the lasers was compared between full-ablative (Er:YAG) and fractional (CO2) modalities. We fabricated poly-L-lactic acid (PLA) and PLA/poly(lactic-co-glycolic acid) (PLGA) nanoparticles by an emulsion-solvent evaporation technique. The mean size of PLA and PLA/PLGA nanocarriers was 237 and 222 nm, respectively. The RA encapsulation percentage in both nanosystems was > 96 %. PLA and PLA/PLGA nanocarriers promoted RA skin deposition by 5- and 3-fold compared to free control. The ablative lasers further enhanced the skin deposition of RA-loaded nanoparticles, with the full-ablative laser showing greater permeation enhancement than the fractional mode. The skin biodistribution assay evaluated by confocal and fluorescence microscopies demonstrated that the laser-assisted nanoparticle delivery achieved a significant dermis and follicular accumulation. The cell-based study indicated a facile uptake of the nanoparticles into the human dermal fibroblasts. The nanoparticulate RA increased type I collagen and elastin production in the UVA-treated fibroblasts. A reduction of matrix metalloproteinase (MMP)-1 was also highlighted in the photoaging cells. The calculation of therapeutic index (TI) by multiplying collagen/elastin elevation percentage and skin deposition predicted better anti-photoaging performance in Er:YAG laser-assisted nanoparticle delivery than CO2 laser. Nanoencapsulation of RA decreased the cytotoxicity against skin fibroblasts. In vivo skin tolerance test on a nude mouse showed less skin damage after topical application of the nanoparticles than free RA. Our results hypothesized that the laser-mediated nanoparticle delivery provided an efficient and safe use for treating photoaging.

Anti-Inflammatory microRNAs for Treating Inflammatory Skin Diseases.

Skin inflammation occurs due to immune dysregulation because of internal disorders, infections, and allergic reactions. The inflammation of the skin is a major sign of chronic autoimmune inflammatory diseases, such as psoriasis, atopic dermatitis (AD), and lupus erythematosus. Although there are many therapies for treating these cutaneous inflammation diseases, their recurrence rates are high due to incomplete resolution. MicroRNA (miRNA) plays a critical role in skin inflammation by regulating the expression of protein-coding genes at the posttranscriptional level during pathogenesis and homeostasis maintenance. Some miRNAs possess anti-inflammatory features, which are beneficial for mitigating the inflammatory response. miRNAs that are reduced in inflammatory skin diseases can be supplied transiently using miRNA mimics and agomir. miRNA-based therapies that can target multiple genes in a given pathway are potential candidates for the treatment of skin inflammation. This review article offers an overview of the function of miRNA in skin inflammation regulation, with a focus on psoriasis, AD, and cutaneous wounds. Some bioactive molecules can target and modulate miRNAs to achieve the objective of inflammation suppression. This review also reports the anti-inflammatory efficacy of these molecules through modulating miRNA expression. The main limitations of miRNA-based therapies are rapid biodegradation and poor skin and cell penetration. Consideration was given to improving these drawbacks using the approaches of cell-penetrating peptides (CPPs), nanocarriers, exosomes, and low-frequency ultrasound. A formulation design for successful miRNA delivery into skin and target cells is also described in this review. The possible use of miRNAs as biomarkers and therapeutic modalities could open a novel opportunity for the diagnosis and treatment of inflammation-associated skin diseases.

Design Space Approach for the Optimization of Green Fluidized Bed Granulation Process in the Granulation of a Poorly Water-Soluble Fenofibrate Using Design of Experiment.

In the pharmaceutical industry, the systematic optimization of process variables using a quality-by-design (QbD) approach is highly precise, economic and ensures product quality. The current research presents the implementation of a design-of-experiment (DoE) driven QbD approach for the optimization of key process variables of the green fluidized bed granulation (GFBG) process. A 32 full-factorial design was performed to explore the effect of water amount (X1; 1-6% w/w) and spray rate (X2; 2-8 g/min) as key process variables on critical quality attributes (CQAs) of granules and tablets. Regression analysis have demonstrated that changing the levels of X1 and X2 significantly affect (p ≤ 0.05) the CQAs of granules and tablets. Particularly, X1 was found to have the pronounced effect on the CQAs. The GFBG process was optimized, and a design space (DS) was built using numerical optimization. It was found that X1 and X2 at high (5.69% w/w) and low (2 g/min) levels, respectively, demonstrated the optimum operating conditions. By optimizing X1 and X2, GFBG could enhance the disintegration and dissolution of tablets containing a poorly water-soluble drug. The prediction error values of dependent responses were less than 5% that confirm validity, robustness and accuracy of the generated DS in optimization of GFBG.

Nanoencapsulation of Tea Catechins for Enhancing Skin Absorption and Therapeutic Efficacy.

Tea catechins are a group of flavonoids that show many bioactivities. Catechins have been extensively reported as a potential treatment for skin disorders, including skin cancers, acne, photoaging, cutaneous wounds, scars, alopecia, psoriasis, atopic dermatitis, and microbial infection. In particular, there has been an increasing interest in the discovery of cosmetic applications using catechins as the active ingredient because of their antioxidant and anti-aging activities. However, active molecules with limited lipophilicity have difficulty penetrating the skin barrier, resulting in low bioavailability. Nevertheless, topical application is a convenient method for delivering catechins into the skin. Nanomedicine offers an opportunity to improve the delivery efficiency of tea catechins and related compounds. The advantages of catechin-loaded nanocarriers for topical application include high catechin loading efficiency, sustained or prolonged release, increased catechin stability, improved bioavailability, and enhanced accumulation or targeting to the nidus. Further, various types of nanoparticles, including liposomes, niosomes, micelles, lipid-based nanoparticles, polymeric nanoparticles, liquid crystalline nanoparticles, and nanocrystals, have been employed for topical catechin delivery. These nanoparticles can improve catechin permeation via close skin contact, increased skin hydration, skin structure disorganization, and follicular uptake. In this review, we describe the catechin skin delivery approaches based on nanomedicine for treating skin disorders. We also provide an in-depth description of how nanoparticles effectively improve the skin absorption of tea catechins and related compounds, such as caffeine. Furthermore, we summarize the possible future applications and the limitations of nanocarriers for topical delivery at the end of this review article.

Boosting the Anticancer Activity of Sunitinib Malate in Breast Cancer through Lipid Polymer Hybrid Nanoparticles Approach.

In the current study, lipid-polymer hybrid nanoparticles (LPHNPs) fabricated with lipoid-90H and chitosan, sunitinib malate (SM), an anticancer drug was loaded using lecithin as a stabilizer by employing emulsion solvent evaporation technique. Four formulations (SLPN1-SLPN4) were developed by varying the concentration of chitosan polymer. Based on particle characterization, SLPN4 was optimized with size (439 ± 5.8 nm), PDI (0.269), ZP (+34 ± 5.3 mV), and EE (83.03 ± 4.9%). Further, the optimized formulation was characterized by FTIR, DSC, XRD, SEM, and in vitro release studies. In-vitro release of the drug from SPN4 was found to be 84.11 ± 2.54% as compared with pure drug SM 24.13 ± 2.67%; in 48 h, release kinetics followed the Korsmeyer-Peppas model with Fickian release mechanism. The SLPN4 exhibited a potent cytotoxicity against MCF-7 breast cancer, as evident by caspase 3, 9, and p53 activities. According to the findings, SM-loaded LPHNPs might be a promising therapy option for breast cancer.

COVID 19 pandemic challenges and their management: A review of medicines, vaccines, patents and clinical trials with emphasis on psychological health issues.

The SARS-CoV-2 (COVID 19) paroxysm is a dominant health exigency that caused significant distress, affecting physical and mental health. Increased mortality, a stressed healthcare system, financial crisis, isolation, and new living and working styles enhanced societal commiseration leading to poor health outcomes. Though people try to maintain good physical health but unfortunately the mental affliction is still ignored. Poor psychological health has emerged as a burgeoning social issue and demands attention. Henceforth, the fundamental objective of this review article is to collate information about COVID-linked physical and psychological agony in diverse population groups with related symptoms and accessible diagnosis techniques. Recent studies have unraveled the fragile mental states of people who have either contracted COVID 19 or had near and dear ones falling prey to it. The impact of the epidemic on the human mind both in short and long-term, with possible risk and preventive factors together with suggested solutions for maintaining good health have also been discussed here. It also enlists the available medications, vaccines and investigational research in the form of patents and clinical trials. This article can be taken as an updated information sheet for COVID 19, accompanied by its management techniques with special emphasis on coping strategies for mental health. Further, it may also assist the policymakers to devise approaches that could enable the public to overcome the pandemic-driven adversity not only in the given situation but also futuristically.

Application of hydrophilic polymers for the preparation of tadalafil solid dispersions: micromeritics properties, release and erectile dysfunction studies in male rats.

The objective of the present study was to improve the dissolution rate and aphrodisiac activity of tadalafil by using hydrophilic polymers. Solid dispersions were prepared by solvent evaporation-Rota evaporator using Koliphore 188, Kollidon® VA64, and Kollidon® 30 polymers in a 1:1 ratio. Prepared tadalafil-solid dispersions (SDs) evaluated for yield, drug content, micromeritics properties, physicochemical characterizations, and aphrodisiac activity assessment. The optimized SDs TK188 showed size (2.175 ± 0.24 µm), percentage of content (98.89 ± 1.23%), yield (87.27 ± 3.13%), bulk density (0.496 ± 0.005 g/cm3), true density (0.646 ± 0.003 g/cm3), Carr's index (23.25 ± 0.81), Hausner ratio (1.303 ± 0.003) and angle of repose (<25°). FTIR spectrums revealed tadalafil doesn't chemically interact with used polymers. XRD and DSC analysis represents TK188 SDs were in the amorphous state. Drug release was 97.17 ± 2.43% for TK188, whereas it was 32.76 ± 2.65% for pure drug at the end of 2 h with 2.96-fold increase in dissolution and followed release kinetics of Korsmeyer Peppa's model. MDT and DE were noted to be 17.48 minutes and 84.53%, respectively. Furthermore, TK188 SDs showed relative improvement in the sexual behavior of the male rats. Thus the developed SDs TK188 could be potential tadalafil carriers for the treatment of erectile dysfunction.

A Novel Approach of Targeting Linezolid Nanoemulsion for the Management of Lymph Node Tuberculosis.

Tuberculosis (TB) represents a major public health problem, globally affecting children and adults. Lymphatic TB is the most common type of extrapulmonary tuberculosis, which affects the peripheral lymph nodes. This burgeoning disease requires a long-term treatment of multiple antibiotics to kill Mycobacterium tuberculosis, resulting in an increased rate of multidrug-resistant tuberculosis. To overcome drug resistance with the first-line antibiotics, linezolid W/O nanoemulsion was developed in this current work. W/O nanoemulsion was prepared by oil phase titration technique using sunflower oil, span 80 and tween 80, and optimized by pseudophase ternary diagrams. The particle size, polydispersity index, zeta potential, viscosity, and refractive index for the optimized formulation were found to be 92.32 nm, 0.066, -21.9 mV, 32.623 cP, and 1.453, respectively. Drug release from the developed nanoemulsion followed the zero-order kinetic. The antimicrobial efficacy study confirms the antibacterial potential of the developed nanoemulsion. In vivo studies conducted on Wistar rats confirms the lymphatic targeting with a high amount of drug at the target organ just after 8 h of dosing. As a result of the foregoing promising results, it may be inferred that the suggested nanoemulsion could be a viable therapy option for lymph node tuberculosis.

Preparation and Characterization of a Novel Mucoadhesive Carvedilol Nanosponge: A Promising Platform for Buccal Anti-Hypertensive Delivery.

Carvedilol (CRV) is a non-selective third generation beta-blocker used to treat hypertension, congestive heart failure and angina pectoris. Oral administration of CRV showed poor bioavailability (25%), which might be ascribed to its extensive first-pass metabolism. Buccal delivery is known to boost drugs bioavailability. The aim of this study is to investigate the efficacy of bilosomes-based mucoadhesive carvedilol nanosponge for enhancing the oral bioavailability of CRV. The bilosomes were prepared, optimized and characterized for particle size, surface morphology, encapsulation efficiency and ex-vivo permeation studies. Then, the optimized formula was incorporated into a carboxymethyl cellulose/hydroxypropyl cellulose (CMC/HPC) composite mixture to obtain buccal nanosponge enriched with CRV bilosomes. The optimized bilosome formula (BLS9), showing minimum vesicle size, maximum entrapment, and highest cumulative in vitro release, exhibited a spherical shape with 217.2 nm in diameter, 87.13% entrapment efficiency, and sustained drug release for up to 24 h. In addition, ex-vivo drug permeation across sheep buccal mucosa revealed enhanced drug permeation with bilosomal formulations, compared to aqueous drug suspension. Consecutively, BLS9 was incorporated in a CMC/HPC gel and lyophilized for 24 h to obtain bilosomal nanosponge to enhance CRV buccal delivery. Morphological analysis of the prepared nanosponge revealed improved swelling with a porosity of 67.58%. The in vivo assessment of rats indicated that CRV-loaded nanosponge efficiently enhanced systolic/diastolic blood pressure, decreased elevated oxidative stress, improved lipid profile and exhibited a potent cardio-protective effect. Collectively, bilosomal nanosponge might represent a plausible nanovehicle for buccal delivery of CRV for effective management of hypertension.

Nanotechnology in Cosmetics and Cosmeceuticals-A Review of Latest Advancements.

Nanotechnology has the potential to generate advancements and innovations in formulations and delivery systems. This fast-developing technology has been widely exploited for diagnostic and therapeutic purposes. Today, cosmetic formulations incorporating nanotechnology are a relatively new yet very promising and highly researched area. The application of nanotechnology in cosmetics has been shown to overcome the drawbacks associated with traditional cosmetics and also to add more useful features to a formulation. Nanocosmetics and nanocosmeceuticals have been extensively explored for skin, hair, nails, lips, and teeth, and the inclusion of nanomaterials has been found to improve product efficacy and consumer satisfaction. This is leading to the replacement of many traditional cosmeceuticals with nanocosmeceuticals. However, nanotoxicological studies on nanocosmeceuticals have raised concerns in terms of health hazards due to their potential skin penetration, resulting in toxic effects. This review summarizes various nanotechnology-based approaches being utilized in the delivery of cosmetics as well as cosmeceutical products, along with relevant patents. It outlines their benefits, as well as potential health and environmental risks. Further, it highlights the regulatory status of cosmeceuticals and analyzes the different regulatory guidelines in India, Europe, and the USA and discusses the different guidelines and recommendations issued by various regulatory authorities. Finally, this article seeks to provide an overview of nanocosmetics and nanocosmeceuticals and their applications in cosmetic industries, which may help consumers and regulators to gain awareness about the benefits as well as the toxicity related to the continuous and long-term uses of these products, thus encouraging their judicious use.