Development of pH-responsive Hydrogel from Copolymers of Artemisia vulgaris Seed Mucilage, Mucin, and poly(methacrylate) for Controlled Delivery of Acyclovir Sodium.

To cope with the constraints of conventional drug delivery systems, site-specific drug delivery systems are the major focus of researchers. The present research developed water-swellable, pH-responsive methacrylic acid-based hydrogel scaffolds of Artemisia vulgaris seed mucilage with mucin and loaded with acyclovir sodium as a model drug. The developed hydrogel discs are evaluated for diverse parameters. Drug loading efficiency in all formulations ranges from 63% to 75%. The hydrogels exhibited pH-dependent swelling, displaying optimum swelling in a phosphate buffer (pH 7.4), and insignificant swelling in an acidic buffer (pH 1.2), in addition, they responded well to electrolyte concentrations. The sol-gel fraction is estimated ranging from 60 to 95%. Dissolution studies unveiled sustained drug release for 24 h in a phosphate buffer of pH 7.4, exhibiting zero-order release kinetics. Moreover, FTIR spectra confirmed the drug-excipient compatibility. SEM photomicrographs revealed a rough and porous surface of hydrogel discs with several pores and channels. The PXRD diffractograms exposed the amorphous nature of the polymeric blends. The findings of acute toxicity studies proved the developed hydrogel network is biocompatible. Therefore, these outcomes connote the newly created network as a smart delivery system, able to dispatch acyclovir sodium into the intestinal segment for a prolonged period.

Intravenous delivery of furosemide using lipid-based versus polymer-based nanocapsules: in vitro and in vivo studies.

OBJECTIVES: Furosemide (FSM), a potent loop diuretic, is used to treat edema due to hypertension, congestive heart failure, and liver and renal failures. FSM applications are limited by its low bioavailability. Our aim is to use different nanoencapsulation strategies to control the release of FSM and enhance its pharmacokinetic properties. METHODS: Two types of FSM-loaded nanocapsules, namely FSM-loaded lipid nanocapsules (LNCs) and polymeric nanocapsules (PNCs), were developed, physicochemically characterized, and subjected to pharmacokinetic and pharmacodynamic studies. Lipid nanocapsules were prepared by the simple phase inversion method using LabrafacTM lipid, while the polymeric nanocapsules were prepared by nanoprecipitation method using polycaprolactone polymer. RESULTS: Transmission electron microscopy ascertains spherical structures, corroborating the nanometric diameter of both types of nanocapsules. The particle size of the optimized FSM-loaded LNCs and FSM-loaded PNCs was 32.19 ± 0.72 nm and 230.7 ± 5.13 nm, respectively. The percent entrapment efficiency was 63.56 ± 1.40% of FSM for the optimized PNCs. The in vitro release study indicated prolonged drug release compared to drug solutions. The two loaded nanocapsules systems succeeded in enhancing the pharmacokinetic parameters in comparison to the marketed FSM solution with superior diuretic activity (p < 0.05). The results of the stability study and the terminal sterilization by autoclave indicated the superiority of LNCs over PNCs in maintaining the physical parameters under storage conditions and the drastic conditions of sterilization. CONCLUSIONS: LNCs and PNCs are considered promising nanosysems for improving the diuretic effect of FSM.

Enhancing Effector Jurkat Cell Activity and Increasing Cytotoxicity against A549 Cells Using Nivolumab as an Anti-PD-1 Agent Loaded on Gelatin Nanoparticles.

The current research investigated the use of gelatin nanoparticles (GNPs) for enhancing the cytotoxic effects of nivolumab, an immune checkpoint inhibitor. The unique feature of GNPs is their biocompatibility and functionalization potential, improving the delivery and the efficacy of immunotherapeutic drugs with fewer side effects compared to traditional treatments. This exploration of GNPs represents an innovative direction in the advancement of nanomedicine in oncology. Nivolumab-loaded GNPs were prepared and characterized. The optimum formulation had a particle size of 191.9 ± 0.67 nm, a polydispersity index of 0.027 ± 0.02, and drug entrapment of 54.67 ± 3.51%. A co-culture experiment involving A549 target cells and effector Jurkat cells treated with free nivolumab solution, and nivolumab-loaded GNPs, demonstrated that the latter had significant improvements in inhibition rate by scoring 87.88 ± 2.47% for drug-loaded GNPs against 60.53 ± 3.96% for the free nivolumab solution. The nivolumab-loaded GNPs had a lower IC50 value, of 0.41 ± 0.01 µM, compared to free nivolumab solution (1.22 ± 0.37 µM) at 72 h. The results indicate that administering nivolumab-loaded GNPs augmented the cytotoxicity against A549 cells by enhancing effector Jurkat cell activity compared to nivolumab solution treatment.

In Vivo Evaluation of Miconazole-Nitrate-Loaded Transethosomal Gel Using a Rat Model Infected with Candida albicans.

Miconazole nitrate (MCNR), an antifungal drug, is used to treat superficial infections. The objective of the current study was to assess the antifungal effectiveness of MCNR-loaded transethosomal gel (MNTG) against Candida albicans in an in vivo rat model. The outcomes were compared with those of the miconazole nitrate gel (MNG) and marketed Daktarin® cream (2%) based on histopathological and hematological studies. The results of the skin irritation test revealed the safety profile of the MNTG. The MNTG demonstrated the greatest antifungal activity in the histological analysis and the visible restoration of the skin, and the rats revealed an apparent evidence of recovery. Compared to the untreated group, the treated group's lymphocyte and white blood cells counts increased, but their eosinophil counts decreased. In conclusion, MNTG exhibited the greatest antifungal activity, which might be connected to the improved skin permeability of the transethosome's nanosized vesicles. Therefore, it could be considered a promising carrier for topical usage and the treatment of cutaneous candidiasis. More clinical research needs to be performed in order to demonstrate its effectiveness and safe usage in humans.

Protein-polysaccharide based double network microbeads improves stability of Bifidobacterium infantis ATCC 15697 in a gastro-Intestinal tract model (TIM-1).

Microencapsulation of probiotics is a main technique employed to improve cell survival in gastrointestinal tract (GIT). The present study investigated the impact of utilizing proteins i.e. Whey Protein Isolates (WPI), Pea Protein Isolates (PPI) or (WPI + PPI) complex based microbeads as encapsulating agents on the encapsulation efficiency (EE), diameter, morphology along with the survival and viability of Bifidobacterium infantis ATCC 15697. Results revealed that WPI + PPI combination had the highest EE% of the probiotics up to 94.09 % and the smoothest surface with less visible holes. WPI based beads revealed lower EE% and smaller size than PPI based ones. In addition, WPI based beads showed rough surface with visible signs of cracks, while PPI beads showed dense surfaces with pores and depressions. In contrast, the combination of the two proteins resulted in compact and smooth beads with less visible pores/wrinkles. The survival in gastrointestinal tract (GIT) was observed through TNO in-vitro gastrointestinal model (TIM-1) and results illustrated that all microbeads shrank in gastric phase while swelled in intestinal phase. In addition, in-vitro survival rate of free cells was very low in gastric phase (18.2 %) and intestinal phase (27.5 %). The free cells lost their viability after 28 days of storage (2.66 CFU/mL) with a maximum log reduction of 6.76, while all the encapsulated probiotic showed more than 106-7 log CFU/g viable cell. It was concluded that encapsulation improved the viability of probiotics in GIT and utilization of WPI + PPI in combination provided better protection to probiotics.

Novel Transethosomal Gel Containing Miconazole Nitrate; Development, Characterization, and Enhanced Antifungal Activity.

Miconazole nitrate (MCNR) is a BCS class II antifungal drug with poor water solubility. Although numerous attempts have been made to increase its solubility, formulation researchers struggle with this significant issue. Transethosomes are promising novel nanocarriers for improving the solubility and penetration of drugs that are inadequately soluble and permeable. Thus, the objective of this study was to develop MCNR-loaded transethosomal gel in order to enhance skin permeation and antifungal activity. MCNR-loaded transethosomes (MCNR-TEs) were generated using the thin film hydration method and evaluated for their zeta potential, particle size, polydispersity index, and entrapment efficiency (EE%). SEM, FTIR, and DSC analyses were also done to characterize the optimized formulation of MCNR-TEs (MT-8). The optimized formulation of MCNR-TEs was incorporated into a carbopol 934 gel base to form transethosomal gel (MNTG) that was subjected to ex vivo permeation and drug release studies. In vitro antifungal activity was carried out against Candida albicans through the cup plate technique. An in vivo skin irritation test was also performed on Wistar albino rats. MT-8 displayed smooth spherical transethosomal nanoparticles with the highest EE% (89.93 ± 1.32%), lowest particle size (139.3 ± 1.14 nm), polydispersity index (0.188 ± 0.05), and zeta potential (-18.1 ± 0.10 mV). The release profile of MT-8 displayed an initial burst followed by sustained release, and the release data were best fitted with the Korsmeyer-Peppas model. MCNR-loaded transethosomal gel was stable and showed a non-Newtonian flow. It was found that ex vivo drug permeation of MNTG was 48.76%, which was significantly higher than that of MNPG (plain gel) (p ≤ 0.05) following a 24-h permeation study. The prepared MCNR transethosomal gel exhibited increased antifungal activity, and its safety was proven by the results of an in vivo skin irritation test. Therefore, the developed transethosomal gel can be a proficient drug delivery system via a topical route with enhanced antifungal activity and skin permeability.

Fast dissolving microneedle patch for pronounced systemic delivery of an antihyperlipidemic drug.

Fast dissolving microneedles (F-dMN) are quite a novel approach delivering specific drug molecules directly into the bloodstream, bypassing the first-pass effect. The present study reported an F-dMN patch to enhance systemic delivery of simvastatin in a patient-friendly manner. The F-dMN patch was developed using polyvinyl pyrrolidone and polyvinyl alcohol and characterized using light microscopy, SEM, XRD, FTIR, mechanical strength, drug content (%), an ex-vivo penetration study, an ex-vivo drug release study, a skin irritation test, and a pharmacokinetics study. The optimized F-dMN patch exhibited excellent elongation of 35.17%, good tensile strength of 9.68 MPa, an appropriate moisture content of 5.65%, and good penetrability up to 560 µm. Moreover, it showed 93.4% of the drug content within the needles and 81.75% in-vitro release. Histopathological findings and a skin irritation study proved that the F-dMN patch was biocompatible and did not cause any sort of irritation on animal skin. Pharmacokinetic parameters of F-dMN patches were improved (Cmax 6.974 µg/ml, tmax 1 hr and AUC 19. 518 µg.h/ml) as compared to tablet Simva 20 mg solution (Cmax 2.485 µg/ml, tmax 1.4 hr and AUC 11.199 µg.h/ml), thus confirming bioavailability enhancement. Moreover, stability studies confirmed the stability of the developed F-dMN patch, as investigated by axial needle fracture force and drug content.

Berberine loaded thermosensitive lipid nanoparticles: in vitro characterization, in silico study, and in vivo anti-arthritic effect.

Thermoresponsive drug delivery systems have been used to treat diseases that cause hyperthermia or elevated body tissue temperatures, viz., rheumatoid arthritis and different cancers. The aim of the study was to enhance berberine (BER) release using thermosensitive nanostructured lipid carriers (TNLCs) through intra-articular administration for the management of arthritis. TNLCs were prepared using binary mixtures of stearic acid and decanoic acid as solid and liquid lipids, respectively. Lipid mixtures with an optimum melting point were assessed using differential scanning calorimetry studies. In vitro characterization of the BER TNLCs included particle size, zeta potential, entrapment efficiency, and drug release at 37 °C and 41 °C. Joint diameter measurement, real-time polymerase chain reaction (RT-PC) analysis, enzyme-linked immunosorbent assay (ELISA) for inflammatory markers, and histological evaluation of the dissected joints were all performed in vivo on rats with adjuvant-induced arthritis. In vitro characterization revealed negatively charged BER-loaded TNLCs with a spherical shape, particle size less than 500 nm, BER entrapment efficiency up to 79%, and a high drug release rate at an elevated temperature of 41 °C. In silico studies revealed the affinity of BER to different formula components and to the measured biomarkers. In vivo assessment of the optimum TNLCs showed that BER TNLCs were superior to the BER solution suspension regarding their effect on inflammatory biomarkers, joint diameter, and histological studies.

Green synthesis of quince/pectin cross-linked superporous hydrogel sponges for pH-regulated sustained domperidone delivery.

The present study aims to utilize green synthesis to fabricate stimuli-responsive, smart, quince/pectin cross-linked hydrogel sponges for the pH-regulated conveyance of domperidone. The designed hydrogel sponges were evaluated for a sol-gel fraction (%), swelling studies and kinetics, drug loading (%), electrolyte-responsive character, scanning electron microscopy (SEM), thermal analysis, drug-excipient compatibility studies (FTIR), X-ray diffraction (XRD) analysis, mechanical testing, in-vitro drug release studies, and acute oral toxicity studies. The drug loading (%) ranged from 67 to 85%. Hydrogel sponges displayed pH-responsive swelling potential, with optimum swelling in a phosphate buffer (pH 7.4) and insignificant swelling in an acidic buffer of pH 1.2. The prepared hydrogel sponges displayed second-order swelling dynamics. The FTIR data revealed the successful fabrication of the hydrogel sponges with the primary drug peaks remaining unchanged, demonstrating excipients-drug compatibility. SEM confirmed the rough, porous surface of hydrogel sponges with numerous cracks. XRD measurements revealed the transformation of the crystalline nature of domperidone into an amorphous one within the developed hydrogel sponges. Dissolution studies revealed little domperidone release in an acidic environment. However, hydrogel sponges exhibited release up to 10 h in phosphate buffer.The sponge's non-toxic or biocompatible character was confirmed through toxicological studies. Thus, the finding indicates that quince/pectin cross-linked hydrogel sponges are durable enough to deliver the domperidone to the gut for a longer time.

Development of Tofacitinib Loaded pH-Responsive Chitosan/Mucin Based Hydrogel Microparticles: In-Vitro Characterization and Toxicological Screening.

Tofacitinib is an antirheumatic drug characterized by a short half-life and poor permeability, which necessitates the development of sustained release formulation with enhanced permeability potential. To achieve this goal, the free radical polymerization technique was employed to develop mucin/chitosan copolymer methacrylic acid (MU-CHI-Co-Poly (MAA))-based hydrogel microparticles. The developed hydrogel microparticles were characterized for EDX, FTIR, DSC, TGA, X-ray diffraction, SEM, drug loading; equilibrium swelling (%), in vitro drug release, sol-gel (%) studies, size and zeta potential, permeation, anti-arthritic activities, and acute oral toxicity studies. FTIR studies revealed the incorporation of the ingredients into the polymeric network, while EDX studies depicted the successful loading of tofacitinib into the network. The thermal analysis confirmed the heat stability of the system. SEM analysis displayed the porous structure of the hydrogels. Gel fraction showed an increasing tendency (74-98%) upon increasing the concentrations of the formulation ingredients. Formulations coated with Eudragit (2% w/w) and sodium lauryl sulfate (1% w/v) showed increased permeability. The formulations equilibrium swelling (%) increased (78-93%) at pH 7.4. Maximum drug loading and release (%) of (55.62-80.52%) and (78.02-90.56%), respectively, were noticed at pH 7.4, where the developed microparticles followed zero-order kinetics with case II transport. Anti-inflammatory studies revealed a significant dose-dependent decrease in paw edema in the rats. Oral toxicity studies confirmed the biocompatibility and non-toxicity of the formulated network. Thus, the developed pH-responsive hydrogel microparticles seem to have the potential to enhance permeability and control the delivery of tofacitinib for the management of rheumatoid arthritis.

Fabrication of Stimuli-Responsive Quince/Mucin Co-Poly (Methacrylate) Hydrogel Matrices for the Controlled Delivery of Acyclovir Sodium: Design, Characterization and Toxicity Evaluation.

Free-radical polymerization technique was adopted to fabricate a stimuli-responsive intelligent quince/mucin co-poly (methacrylate) hydrogel for the controlled delivery of acyclovir sodium. The developed hydrogel matrices were appraised using different parameters, such as drug loading (%), swelling kinetics, pH- and electrolyte-responsive swelling, and sol-gel fraction. Drug-excipient compatibility study, scanning electron microscopy, thermal analysis, powder X-ray diffraction (PXRD) analysis, in vitro drug release studies, drug release kinetics and acute oral toxicity studies were conducted. The results of drug loading revealed an acyclovir sodium loading of 63-75% in different formulations. The hydrogel discs exhibited pH-responsive swelling behavior, showing maximum swelling in a phosphate buffer with a pH of 7.4, but negligible swelling was obvious in an acidic buffer with a pH of 1.2. The swelling kinetics of the developed hydrogel discs exhibited second-order kinetics. Moreover, the hydrogel discs responded to the concentration of electrolytes (CaCl2 and NaCl). The results of the FTIR confirm the formation of the hydrogel via free-radical polymerization. However, the major peaks of acyclovir remain intact, proving drug-excipient compatibility. The results of the SEM analysis reveal the porous, rough surface of the hydrogel discs with multiple cracks and pores over the surface. The results of the PXRD disclose the amorphous nature of the fabricated hydrogel. The dissolution studies showed a minor amount of acyclovir sodium released in an acidic environment, while an extended release up to 36 h in the phosphate buffer was observed. The drug release followed Hixen-Crowell's kinetics with Fickian diffusion mechanism. The toxicity studies demonstrated the non-toxic nature of the polymeric carrier system. Therefore, these results signify the quince/mucin co-poly (methacrylate) hydrogel as a smart material with the potential to deliver acyclovir into the intestine for an extended period of time.

Development and Evaluation of Cellulose Derivative and Pectin Based Swellable pH Responsive Hydrogel Network for Controlled Delivery of Cytarabine.

In the present study, pH-sensitive, biodegradable, and biocompatible Na-CMC/pectin poly(methacrylic acid) hydrogels were synthesized using an aqueous free radical polymerization technique and encapsulated by cytarabine (anti-cancer drug). The aim of the project was to sustain the plasma profile of cytarabine through oral administration. Sodium carboxymethyl cellulose (Na-CMC) and pectin were cross-linked chemically with methacrylic acid (MAA) as a monomer, using methylene bisacrylamide (MBA) as cross-linker and ammonium per sulfate (APS) as an initiator. Prepared hydrogel formulations were characterized for their texture, morphology, cytarabine loading efficiency, compositional and structural properties, thermal nature, stability, swelling response, drug release profile (pH 1.2 and pH 7.4), and in-vivo pharmacokinetic evaluation. Cytarabine-loaded hydrogels were also evaluated for their safety profile by carrying out toxicity studies in rabbits. Results demonstrated efficient encapsulation of cytarabine into the prepared network with loading ranging from 48.5-82.3%. The highest swelling ratio of 39.38 and maximum drug release of 83.29-85.27% were observed at pH 7.4, highlighting the pH responsiveness of the grafted system. Furthermore, cytarabine maximum release was noticed over 24 h, ensuring a sustained release response for all formulations. Histopathological studies and hemolytic profiles confirmed that the prepared hydrogel system was safe, biocompatible, and non-irritant, showing no symptoms of any toxicities and degeneration in organs. Moreover, pharmacokinetic estimation of the cytarabine-loaded hydrogel showed a remarkable increase in the plasma half-life from 4.44 h to 9.24 h and AUC from 22.06 µg/mL.h to 56.94 µg/mL.h. This study revealed that the prepared hydrogel carrier system has excellent abilities in delivering the therapeutic moieties in a controlled manner.

Ethyl lauroyl arginate-based hydrophobic ion pair complex in lipid nanocapsules: A novel oral delivery approach of rosmarinic acid for enhanced permeability and bioavailability.

Limited oral bioavailability due to high hydrophilicity restricts the beneficial use of Rosmaranic acid (RM) that is characterized by many biological and pharmacological effects. The present work was addressed to extract RM from Rosmarinus officinalis L. leaves and then increase its lipophilicity and permeability through the application of hydrophobic ion pair (HIP) approach using ethyl lauroyl arginate (ELA) as a novel counter-ion. Different RM:ELA ratios were screened to optimize HIP formation process. The encapsulation of the optimized HIP into lipid nanocapsules (LNCs) was then achieved to facilitate oral administration. The results of % transmittance, % complexation efficiency (87.32 ± 0.19%) and partition coefficient revealed the successful formation of the HIP complex occurred at RM:ELA molar ratio of 1:2. The formed HIP was successfully loaded into spherical small sized (39.32 ± 0.18 nm) LNCs. The ex vivo permeability studies across porcine intestine showed that the cumulative RM amount permeated/area after 6 h from HIP and LNCs were 3.79 ± 0.57 and 5.71 ± 0.32 µg/cm2, respectively. Pharmacokinetic study results showed that the maximum RM concentrations in plasma (Cmax) can be arranged in a descending manner as follows; 61.33 ± 8.89 < 42.13 ± 11.22 < 20.96 ± 3.12 ng/ml attained after 4.80, 8.00 and 10.40 h in case of LNC, HIP and solution, respectively. Moreover, the HIP and LNC formulae showed higher total drug amounts in plasma reaching 1.46 and 1.88-fold relative to RM solution, respectively. In conclusion, the HIP complex and HIP loaded LNCs prosper in enhancing the permeability and absorption of the low permeable drugs.

pH Responsive Hydrogels for the Delivery of Capecitabine: Development, Optimization and Pharmacokinetic Studies.

The objective of the current study was to achieve a sustained release profile of capecitabine (CAP), an anticancer agent frequently administered in conventional dosage form due to its short plasma half-life. A drug-loaded smart pH responsive chitosan/fenugreek-g-poly (MAA) hydrogel was synthesized by an aqueous free radical polymerization technique. The developed network was evaluated for capecitabine loading %, swelling response, morphology, structural and compositional characteristics, and drug release behavior. Significantly higher swelling and in vitro drug release rate were exhibited by formulations at pH 7.4 than at pH 1.2, demonstrating the pH responsive character of hydrogels. Swelling percentage and CAP loading ranged within 74.45-83.54% and 50.13-72.43%, respectively. Maximum release, up to 93%, was demonstrated over 30 h, evidencing the controlled release pattern of CAP from hydrogels. The optimized formulation was further screened for acute oral toxicity studies. No signs of oral, dermal, or ocular toxicities were noticed, confirming safety evidence of the network. Furthermore, pharmacokinetic analysis demonstrated the sustained release response of CAP from hydrogels as confirmed by a significant increase in plasma half-life (t1/2) (13 h) and AUC (42.88 µg h/mL) of CAP. Based on these findings, fabricated hydrogels are strongly recommended as a biocompatible carrier for colorectal delivery of active agents.

Chitosan nanoparticles for intranasal delivery of olmesartan medoxomil: Pharmacokinetic and pharmacodynamic perspectives.

Nasal drug delivery has the potential to improve the systemic bioavailability of drugs with low oral bioavailability. Olmesartan medoxomil (OLM) is one of the most popular drugs for the treatment of hypertension with poor oral bioavailability of approximately 26 %. In this context, the goal of this work was to synthesize chitosan nanoparticles (CS NPs) loaded with OLM using the ionotropic gelation method to enhance the bioavailability and decrease oral side effects through nasal route. The particle size (PS), zeta potential (ZP), entrapment efficiency (%EE), and ex-vivo transmucosal permeation study of CS NPs were all evaluated. The pharmacokinetic and pharmacodynamic studies of selected formula compared to oral and nasal OLM suspensions were conducted. Successful formation of spherically shaped OLM CS NPS in the nano-range (240.02-344.45 nm) favorable for the intranasal absorption with high %EE (75.2-83.51 %) was achieved. The ability of OLM CS NPs to permeate efficiently across the nasal mucosa was proven in an ex vivo permeation experiment. Pharmacokinetic study demonstrated that the intranasal administration of OLM CS NPs exhibited improved bioavailability by 11.3-folds relative to oral OLM suspension as indicated by higher AUC value. The superior effect of intranasal OLM CS NPs was also accentuated in l-NAME induced hypertensive rats compared to intranasal and oral OLM suspension by reducing the high blood pressure (BP) and improving the heart rate (HR) of the induced group. Histological examinations revealed no damage occurred to nasal mucosa. In conclusion, OLM CS NPs had the ability to significantly improve the bioavailability of OLM and decrease BP and HR, suggesting the potential application of CS NPs as a promising carrier for the systemic delivery of OLM via intranasal route.

Development and Evaluation of Novel Leflunomide SPION Bioemulsomes for the Intra-Articular Treatment of Arthritis.

Systemic treatments for rheumatoid arthritis are associated with many side effects. This study aimed to minimize the side effects associated with the systemic administration of leflunomide (LEF) by formulating LEF-loaded emulsomes (EMLs) for intra-articular administration. Additionally, EMLs were loaded with supramagnetic nanoparticles (SPIONs) to enhance joint localization, where a magnet was placed on the joint area after intra-articular administration. Full in vitro characterization, including colloidal characteristics, entrapment efficiency, and in vitro release were conducted besides the in vivo evaluation in rats with adjuvant-induced arthritis. In vivo study included joint diameter measurement, X-ray radiographic analysis, RT-PCR analysis, Western blotting, ELISA for inflammatory markers, and histopathological examination of dissected joints. The particle size and entrapment efficiency of the selected LEF SPION EMLs were 198.2 nm and 83.7%, respectively. The EMLs exhibited sustained release for 24 h. Moreover, in vivo evaluation revealed LEF SPION EMLs to be superior to the LEF suspension, likely due to the increase in LEF solubility by nanoencapsulation that improved the pharmacological effects and the use of SPION that ensured the localization of EMLs in the intra-articular cavity upon administration.

Rosmarinus officinalis L. hexane extract: phytochemical analysis, nanoencapsulation, and in silico, in vitro, and in vivo anti-photoaging potential evaluation.

A shift towards natural anti-aging ingredients has spurred the research to valorize traditionally used plants. In this context, Rosmarinus officinalis L. was evaluated for its photoprotective, antioxidant, anti-inflammatory, and anti-wrinkling properties. GC/MS and LC-ESI-HRMS based phytochemical profiling of rosemary leaves hexane extract resulted in the identification of 47 and 31 compounds, respectively and revealed rich content in triterpenoids, monoterpenoids and phenolic diterpenes. In vitro assays confirmed the antioxidant, anti-aging, and wound healing potential of rosemary extract along with a good safety profile, encouraging further development. A systematic molecular modelling study was conducted to elucidate the mechanistic background of rosemary anti-aging properties through the inhibitory effects of its major constituents against key anti-aging targets viz. elastase, collagenase, and hyaluronidase. Development of rosemary extract lipid nanocapsules-based mucoadhesive gels was performed to improve skin contact, permeation, and bioavailability prior to in vivo testing. The developed formulae demonstrated small particle size (56.55-66.13 nm), homogenous distribution (PDI of 0.207-0.249), and negatively charged Zeta potential (- 13.4 to - 15.6). In UVB-irradiated rat model, topical rosemary hexane extract-loaded lipid nanocapsules-based gel provided photoprotection, restored the antioxidant biochemical state, improved epidermal and dermal histological features, and decreased the level of inflammatory and wrinkling markers. The use of rosemary hexane extract in anti-aging and photoprotective cosmeceuticals represents a safe, efficient, and cost-effective approach.

MXene (Ti3C2Tx)-Embedded Nanocomposite Hydrogels for Biomedical Applications: A Review.

Polymeric nanocomposites have been outstanding functional materials and have garnered immense attention as sustainable materials to address multi-disciplinary problems. MXenes have emerged as a newer class of 2D materials that produce metallic conductivity upon interaction with hydrophilic species, and their delamination affords monolayer nanoplatelets of a thickness of about one nm and a side size in the micrometer range. Delaminated MXene has a high aspect ratio, making it an alluring nanofiller for multifunctional polymer nanocomposites. Herein, we have classified and discussed the structure, properties and application of major polysaccharide-based electroactive hydrogels (hyaluronic acid (HA), alginate sodium (SA), chitosan (CS) and cellulose) in biomedical applications, starting with the brief historical account of MXene's development followed by successive discussions on the synthesis methods, structures and properties of nanocomposites encompassing polysaccharides and MXenes, including their biomedical applications, cytotoxicity and biocompatibility aspects. Finally, the MXenes and their utility in the biomedical arena is deliberated with an eye on potential opportunities and challenges anticipated for them in the future, thus promoting their multifaceted applications.

Optimization of Hyaluronate-Based Liposomes to Augment the Oral Delivery and the Bioavailability of Berberine.

Various perspectives had been utilized to enhance the poor intestinal permeability and bioavailability of drugs with low water solubility. Berberine (Brb) is a unique molecule that possesses multiple therapeutic activities such as antimicrobial, anti-inflammatory, antioxidant and anti-hyperglycemic effects. To improve Brb permeability and bioavailability, this study presents a newly developed formulation, namely Brb hyaluronate-based liposomes, prepared by using film hydration method and characterized by dynamic light scattering measurements, entrapment efficiency percentage (EE%), transmission electron microscope (TEM), in vitro drug release and physical stability. The bioavailability of the selected formulations was assessed in vivo after oral administration to rats. The results revealed an enhanced effect of hyaluronic acid on the entrapment efficiency, reaching 78.1 ± 0.1% with mean size 520.7 ± 19.9 nm. Sustained release of Brb was recorded up to 24 h in comparison to Brb solution. Physical stability was maintained for three months at refrigeration temperature. Results of pharmacokinetics studies indicated the potential of the liposomal formulation to increase the oral bioavailability of Brb and to accelerate its entry into the bloodstream. The obtained results are accredited to the lipophilic nature of the prepared system, resembling the structural features of bio-membrane, in addition to their small size that enhances intestinal penetration.

The Tragedy of Alzheimer's Disease: Towards Better Management via Resveratrol-Loaded Oral Bilosomes.

Alzheimer's disease (AD) is a neurodegenerative disease where oxidative stress plays a major role as a key pathologic factor. The study aims to develop resveratrol (RES)-loaded bilosomes for oral use, aiming to enhance RES bioavailability. RES-loaded bilosomes were prepared using the thin-film hydration technique. The effect of different formulation variables viz. the number of extrusion cycles, drug concentration and the effect of pH of the medium and cholesterol addition on the physicochemical properties of the prepared bilosomes was investigated. Results revealed the successful entrapment of RES into bilosomes. An optimized formula was selected, showing the lowest particle size (189 ± 2.14), acceptable PDI (0.116) and entrapment efficiency (76.2 ± 1.36). In vivo studies on a streptozotocin-induced animal model of AD showed the preeminence of bilosomes over traditional drug suspension to enhance mice memory via Y-maze and Morris water maze tests. Moreover, mice treated with the optimized formula exhibited decreased COX2, IL-6, amyloid-beta peptide and Tau protein levels compared to the drug suspension. Immuno-histochemical analysis revealed a significant decrease of glial fibrillary acidic protein values and microglial cell count in mice treated with bilosomes. Finally, it could be advocated that RES-loaded bilosomes could be a promising drug delivery system to control AD.