Novel Thermosensitive and Mucoadhesive Nasal Hydrogel Containing 5-MeO-DMT Optimized Using Box-Behnken Experimental Design.

We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m.

Particulate 3D Hydrogels of Silk Fibroin-Pluronic to Deliver Curcumin for Infection-Free Wound Healing.

Skin is the largest protective tissue of the body and is at risk of damage. Hence, the design and development of wound dressing materials is key for tissue repair and regeneration. Although silk fibroin is a known biopolymer in tissue engineering, its degradation rate is not correlated with wound closure rate. To address this disadvantage, we mimicked the hierarchical structure of skin and also provided antibacterial properties; a hydrogel with globular structure consisting of silk fibroin, pluronic F127, and curcumin was developed. In this regard, the effect of pluronic and curcumin on the structural and mechanical properties of the hydrogel was studied. The results showed that curcumin affected the particle size, crystallinity, and ultimate elongation of the hydrogels. In vitro assays confirmed that the hydrogel containing curcumin is not cytotoxic while the diffused curcumin and pluronic provided a considerable bactericidal property against Methicillin-resistant Staphylococcus aureus. Interestingly, presence of pluronic caused more than a 99% reduction in planktonic and adherent bacteria in the curcumin-free hydrogel groups. Moreover, curcumin improved this number further and inhibited bacteria adhesion to prevent biofilm formation. Overall, the developed hydrogel showed the potential to be used for skin tissue regeneration.

Comparative Study of TPGS and Soluplus Polymeric Micelles Embedded in Poloxamer 407 In Situ Gels for Intranasal Administration.

This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic options are required. Dexamethasone was encapsulated into three different polymeric micelle formulations: Soluplus or TPGS-only and their mixed combinations. Dynamic light scattering measurements proved that the particles have a micelle size less than 100 nm in monodisperse distribution, with high encapsulation efficiency above 80% and an at least 7-fold water solubility increase. Tobramycin, as an antimicrobial agent, was co-formulated into the in situ gelling systems which were optimized based on gelation time and gelation temperature. The sol-gel transition takes place between 32-35 °C, which is optimally below the temperature of the nasal cavity in a quick manner below 5 min, a suitable strategic criterion against the mucociliary clearance. In vitro drug release and permeability studies confirmed a rapid kinetics in the case of the encapsulated dexamethasone accompanied with a sustained release of tobramycin, as the hydrophilic drug.

Modeling, the Optimization of the Composition of Emulgels with Ciclopirox Olamine, and Quality Assessment.

The design and development of pharmaceutical products require specific knowledge, time, and investment. Response surface methodology (RSM) is a widely used technique in the design of experiments (DoE) to optimize various processes and products. The aim of this study was to model and produce experimental emulgels containing 1% ciclopirox olamine and to evaluate their physical, rheological, and mechanical properties and their ability to release ciclopirox olamine. The objective was to optimize the composition of the experimental emulgel containing 1% ciclopirox olamine by applying a central composite design based on selected criteria. The surfactant (polysorbate 80) had the greatest influence on the physical, rheological, and mechanical properties of the emulgels, as well as on the release of ciclopirox olamine from these systems. During the optimization process, an emulgel of optimal composition was generated containing 38.27% mineral oil, 6.56% polysorbate 80, and 55.17% hydrogel containing 1% ciclopirox olamine, meeting specified criteria (dependent variables) including the maximum flux of ciclopirox olamine, the minimum sol-gel transition temperature (Tsol/gel), and the minimum particle size of the oil phase. The oil phase particle size (D50) of this emulgel was determined to be 0.337 µm, the system Tsol/gel was 9.1 °C, and the flux of ciclopirox olamine from this gel matrix was calculated to be 1.44 mg/cm2. This emulgel of optimal composition could be used to treat fungal skin diseases.

Formulation, Optimization and In-Vivo Characterization of Thermosensitive In-Situ Nasal Gel Loaded with Bacoside a for Treatment of Epilepsy.

The intranasal route has demonstrated superior systemic bioavailability due to its extensive surface area, the porous nature of the endothelial membrane, substantial blood flow, and circumvention of first-pass metabolism. In traditional medicinal practices, Bacopa monnieri, also known as Brahmi, is known for its benefits in enhancing cognitive functions and potential effects in epilepsy. This study aimed to develop and optimize a thermosensitive in-situ nasal gel for delivering Bacoside A, the principal active compound extracted from Bacopa monnieri. The formulation incorporated Poloxamer 407 as a thermogelling agent and HPMC K4M as the Mucoadhesive polymer. A 32-factorial design approach was employed for Optimization. Among the formulations. F7 exhibited the most efficient Ex-vivo permeation through the nasal mucosa, achieving 94.69 ± 2.54% permeation, and underwent a sol-gel transition at approximately 30.48 °C. The study's factorial design revealed that gelling temperature and mucoadhesive strength were critical factors influencing performance. The potential of in-situ nasal Gel (Optimized Batch-F7) for the treatment of epilepsy was demonstrated in an in-vivo investigation using a PTZ-induced convulsion model. This formulation decreased both the occurrence and intensity of seizures. The optimized formulation F7 showcases significant promise as an effective nasal delivery system for Bacoside A, offering enhanced bioavailability and potentially increased efficacy in epilepsy treatment.

Integrated In Vivo and In Vitro Evaluation of a Powder-to-Hydrogel, Film-Forming Polymer Complex Base with Tissue-Protective and Microbiome-Supportive Properties.

The study aimed to perform a comprehensive in vitro and in vivo evaluation of a newly developed, patent-pending, powder-to-hydrogel, film-forming polymer complex base, which possesses tissue-protective and microbiome-supportive properties, and to compare its characteristics with poloxamer 407. The study used a combination of in vitro assays, including tissue viability and cell migration, and in vivo wound healing evaluations in male diabetic mice. Microbiome dynamics at wound sites were also analyzed. The in vitro assays demonstrated that the polymer complex base was non-cytotoxic and that it enhanced cell migration over poloxamer 407. In vivo, the polymer complex base demonstrated superior wound healing capabilities, particularly in combination with misoprostol and phenytoin, as evidenced by the reduced wound area and inflammation scores. Microbiome analysis revealed favorable shifts in bacterial populations associated with the polymer complex base-treated wounds. The polymer complex base demonstrates clinical significance in wound care, potentially offering improved healing, safety and microbiome support. Its transformative properties and efficacy in drug delivery make it a promising candidate for advanced wound care applications, particularly in chronic wound management.

Poloxamer 407 modified collagen/ß-tricalcium phosphate scaffold for localized delivery of alendronate.

Systemic administration of alendronate is associated with various adverse reactions in clinical settings. To mitigate these side effects, poloxamer 407 (P-407) modified with cellulose was chosen to encapsulate alendronate. This drug-loaded system was then incorporated into a collagen/ß-tricalcium phosphate (ß-TCP) scaffold to create a localized drug delivery system. Nuclear magnetic resonance spectrum and rheological studies revealed hydrogen bonding between P-407 and cellulose as well as a competitive interaction with water that contributed to the delayed release of alendronate (ALN). Analysis of the degradation kinetics of P-407 and release kinetics of ALN indicated zero-order kinetics for the former and Fickian or quasi-Fickian diffusion for the latter. The addition of cellulose, particularly carboxymethyl cellulose (CMC), inhibited the degradation of P-407 and prolonged the release of ALN. The scaffold's structure increased the contact area of P-407 with the PBS buffer, thereby, influencing the release rate of ALN. Finally, biocompatibility testing demonstrated that the drug delivery system exhibited favorable cytocompatibility and hemocompatibility. Collectively, these findings suggest that the drug delivery system holds promise for implantation and bone healing applications.

Bioavailability Enhancement of BCS Class II Raloxifene Hydrochloride by Inclusion Complex and Solid Dispersion Techniques.

OBJECTIVE: Raloxifene hydrochloride (RLX) is used extensively in the treatment of osteoporosis, only 2% of RLX's bioavailability remains after a significant first pass metabolism. Besides coming from BCS class II, RLX is not very soluble in water. Thus, the goal of the current study was to improve RLX solubility by creating an inclusion complex using ß cyclodextrin (ß-CD) as a carrier and solid dispersion with Poloxamer 407. METHODS: Inclusion complex and solid dispersion were made using a variety of techniques, including kneading, co-precipitation, and physical mixing and solid dispersion using different drug to carrier ratios (1:1, 1:2 and 1:3). RESULTS: Inclusion complex made using the co-precipitation method had shown 9-fold improvements in water solubility when compared with plain RLX. In order to assess the optimized complex's compatibility, thermal analysis, and crystallinity, X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopy were used. The XRD and DSC study's results indicated that RLX changed from a crystalline to an amorphous state. IC-6 exhibits effective water solubility based on the outcome. However, upon comparison of the two techniques, the ß-CD complexation method shown an impressive rise in drug solubility when compared to solid dispersion.

Mixed-Micelle in Situ Gel as a Candidate for Oral Inflammatory Ulcerative Diseases.

The current treatment for oral inflammatory ulcerative diseases has limitations. In situ forming hydrogels have shown great potential to deliver therapeutic substances for drug delivery to the buccal cavity. This study aimed to prepare and characterize lipid- and surfactant-based mixed micelle in situ gel (MIG) and evaluate whether it can offer more favorable properties than the in situ gel for effective treatment of the disease. Dexamethasone was incorporated into the MIGs particles, based on Poloxamer 407 and chitosan. The lower gelation time at 37 ℃ was considered a criterion to select superior formulations among the different lipid- and surfactant-based candidates. Further characterization was performed to evaluate the opted formulations regarding morphology, physical stability, rheology, texture, and release profile. All formulations were thermoresponsive and had a shorter gelation time as the temperature increased. Dexamethasone was released in a highly controlled manner, and morphological evaluation revealed that the mixed micelle in situ gels had spherical nanoparticles. Thixotropic behavior was observed in all MIGs, indicating a prolonged retention time of the formulation after oral administration. This study has shown that among different MIGs, the one with oleic acid is a more promising candidate than the in situ gel and other MIGs for drug delivery to the buccal cavity.

In-situ gel injection of poloxamer-based metamizole provides long-acting antipyretic effects.

Metamizole easily decomposes in the body and has a short action time and low bioavailability. Hence, frequent injection administrations are needed to maintain its plasma concentration. This study aimed to design and develop an in-situ gel based on poloxamer 407 and 188 to assess its long-acting antipyretic effects. The in-situ gel-forming systep00m with optimum sol-gel transition temperature of 35.9 °C to 36.3 °C could be formed using a combination of P407 at a ratio of 21-23% (w/v) and P188 at a ratio of 2-4% (w/v). In vitro erosion test showed that the in-situ gel's erosion curve and the metamizole release rate both reached about 90% at 6 h, revealing a good linear relationship between the in-situ gel erosion and the drug release. In vitro release test with dialysis tube showed that the release of metamizole from the in-situ gel was remarkably slower than that from the metamizole solution. Approximately 85% of metamizole was released in the dialysis tube within 7 h, implying a good sustained release effect. Pharmacodynamic study showed that the in-situ gel injection extended the action time of metamizole relative to that when using the metamizole solution. Pharmacokinetic study revealed that the in-situ gel significantly increased the blood serum half-life and area under the curve), contributing to a sustained release and improved bioavailability. This study demonstrated that in-situ gel injection could prolong the action of metamizole in the body to reduce the number of administration times and has good clinical application.

Improving material properties of a poloxamer P407 hydrogel-based hydroxyapatite bone substitute material by adding silica-A comparative in vivo study.

The structure and handling properties of a P407 hydrogel-based bone substitute material (BSM) might be affected by different poloxamer P407 and silicon dioxide (SiO2) concentrations. The study aimed to compare the mechanical properties and biological parameters (bone remodeling, BSM degradation) of a hydroxyapatite: silica (HA)-based BSM with various P407 hydrogels in vitro and in an in vivo rat model. Rheological analyses for mechanical properties were performed on one BSM with an SiO2-enriched hydrogel (SPH25) as well on two BSMs with unaltered hydrogels in different gel concentrations (PH25 and PH30). Furthermore, the solubility of all BSMs were tested. In addition, 30 male Wistar rats underwent surgical creation of a well-defined bone defect in the tibia. Defects were filled randomly with PH30 (n = 15) or SPH25 (n = 15). Animals were sacrificed after 12 (n = 5 each), 21 (n = 5 each), and 63 days (n = 5 each). Histological evaluation and histomorphometrical quantification of new bone formation (NB;%), residual BSM (rBSM;%), and soft tissue (ST;%) was conducted. Rheological tests showed an increased viscosity and lower solubility of SPH when compared with the other hydrogels. Histomorphometric analyses in cancellous bone showed a decrease of ST in PH30 (p = .003) and an increase of NB (PH30: p = .001; SPH: p = .014) over time. A comparison of both BSMs revealed no significant differences. The addition of SiO2 to a P407 hydrogel-based hydroxyapatite BSM improves its mechanical stability (viscosity, solubility) while showing similar in vivo healing properties compared to PH30. Additionally, the SiO2-enrichment allows a reduction of poloxamer ratio in the hydrogel without impairing the material properties.

Amikacin in 30% poloxamer 407 is a versatile local therapy with method of application and outcome documented in 29 dogs.

OBJECTIVE: To report the clinical use, adverse events, and outcomes after using amikacin in 30% poloxamer 407 (amikacin-P407) during open wound management or in a closed wound application in dogs. ANIMALS: 29 client-owned dogs. METHODS: Medical records from January 2017 to August 2023 from a single hospital were reviewed for dogs that received amikacin-P407 in an open or closed wound application. Information reviewed included signalment, nature of wound and/or surgical site infection (SSI), bacterial cultures, amikacin dose, gel volume, route of administration, estimated wound surface area, biochemistry parameters, urine casts, wound progression, and general clinical outcome. RESULTS: Amikacin-P407 was applied during open wound care (10 dogs), via injection (5 dogs), and at time of wound closure (13 dogs) and was used both in open and closed wound management (1 dog). Wounds were associated with SSIs in 18 of 30 sites. Multidrug resistance was noted in 21 of 30 preapplication cultures. Median amikacin dose was 14.5 mg/kg (range, 3 to 59.5 mg/kg), median total volume was 5.0 mL (range, 1 to 12 mL), and median tissue surface area was 6.6 cm2 (range, 1.6 to 36 cm2), for a local wound dose of 62.5 mg/cm2 (range, 6.9 to 214.3 mg/cm2). No short-term adverse local or systemic effects were noted in any wounds or dogs. No dehiscence was seen in 17 of 19 closed sites. CLINICAL RELEVANCE: The results of this case series suggested that Amikacin-P407 can be applied in a variety of ways with no adverse effects. Amikacin-P407 may be considered in open wound management or in a closed setting for infected wounds and SSIs.

Slightly viscous dispersions of mucoadhesive polymers as vehicles for nasal administration of dopamine and grape seed extract-loaded solid lipid nanoparticles.

With the aim to find an alternative vehicle to the most used thermosensitive hydrogels for efficient nanotechnology-based nose-to-brain delivery approach for Parkinson's disease (PD) treatment, in this work we evaluated the Dopamine (DA) and the antioxidant grape seed-derived pro-anthocyanidins (Grape Seed Extract, GSE) co-loaded solid lipid nanoparticles (SLNs) put in slight viscous dispersions (SVDs). These SVDs were prepared by dispersion in water at low concentrations of mucoadhesive polymers to which SLN pellets were added. For the purpose, we investigated two polymeric blends, namely Poloxamer/Carbopol (PF-127/Carb) and oxidized alginate/Hydroxypropylmethyl cellulose (AlgOX/HPMC). Rheological studies showed that the two fluids possess Newtonian behaviour with a viscosity slightly higher that water. The pH values of the SVDs were mainly within the normal range of nasal fluid as well as almost no osmotic effect was associated to both SVDs. All the SVDs were capable to provide DA permeation through nasal porcine mucosa. Moreover, it was found that PF-127/Carb blend possesses penetration enhancer capability better than the Alg OX/HPMC combination. Flow cytometry studies demonstrated the uptake of viscous liquids incorporating fluorescent SLNs by human nasal RPMI 2650 cell in time-dependent manner. In conclusion, the SVD formulations may be considered promising alternatives to thermosensitive hydrogels strategy. Moreover, in a broader perspective, such SVD formulations may be also hopeful for treating various neurological diseases beyond PD treatment.

Advanced Chemical and Imaging Methods for Studying Structure Morphology and Excipients Solid State Transformations in Pharmaceutical Multiparticulate Formulations.

The formulation of paediatric medicines faces significant challenges to meet the requirements for safe and accurate administration, while maintaining a suitable taste. Multiparticulate formulations have a strong potential to address these challenges because they combine dose flexibility with ease of administration. Understanding the stability of multiparticulate formulations over storage as a function of time and environmental parameters, such as humidity and temperature, is important to manage their commercialisation and use. In this work, we have expanded the toolkit of available techniques for studying multiparticulates beyond those such as scanning electron microscopy (SEM) and confocal laser scanning microscopy. We include advanced methods of environmentally-controlled SEM to monitor temperature- and humidity-induced changes in-situ, and a variety of Raman spectroscopies including stimulated Raman scattering microscopy to identify and localise the different ingredients at the surface and inside the multiparticulates. These techniques allowed unprecedented monitoring of specific changes to the particulate structure and distribution of individual ingredients due to product aging. These methods should be considered as valuable novel tools for in-depth characterisation of multiparticulate formulations to further understand chemical changes occurring during their development, manufacturing and long-term storage. We envisage these techniques to be useful in furthering the development of future medicine formulations.

Enhanced efficacy of ß-carotene loaded solid lipid nanoparticles optimized and developed via central composite design on breast cancer cell lines.

ß-carotene is obtained from both plants and animals and has been the subject of intense research because of its provitamin-A, antioxidant, and anticancer effects. Its limited absorption and oxidative degradation significantly reduce its antitumor efficacy when taken orally. In our study, we utilize a central composite design to develop "bio-safe and highly bio-compatible" solid lipid nanoparticles (SLNs) by using only the combination of palmitic acid and poloxamer-407, a block co-polymer as a surfactant. The current research aim to develop and characterize SLNs loaded with ß-carotene to improve their bioavailability and therapeutic efficacy. In addition, the improved cytotoxicity of solid lipid nanoparticles loaded with ß-carotene was screened in-vitro in human breast cancer cell lines (MCF-7). The nanoparticles exhibits good stability, as indicated by their mean zeta potential of -26.3 ± 1.3 mV. The particles demonstrated high drug loading and entrapment capabilities. The fabricated nanoparticle's prolonged release potential was shown by the in-vitro release kinetics, which showed a first-order release pattern that adhered to the Higuchi model and showed a slow, linear, and steady release over 48 h. Moreover, a diffusion-type release mechanism was used to liberate ß-carotene from the nanoparticles. For six months, the nanoparticles also showed a notable degree of physical stability. Lastly, using the MTT assay, the anti-cancer properties of ß-carotene-loaded solid lipid nanoparticles were compared with intact ß-carotene on MCF-7 cell lines. The cytotoxicity tests have shown that the encapsulation of ß-carotene in the lipid bilayers of the optimized formulation does not interfere with the anti-cancer activity of the drug. When compared to standard ß-carotene, ß-carotene loaded SLNs showed enhanced anticancer efficacy and it is a plausible therapeutic candidate for enhancing the solubility of water-insoluble and degradation-sensitive biotherapeutics like ß-carotene.

Enhancing breast cancer treatment: Comprehensive study of gefitinib-loaded poloxamer 407/TPGS mixed micelles through design, development, in-silico modelling, In-Vitro testing, and Ex-Vivo characterization.

Breast cancer continues to pose a substantial global health challenge, emphasizing the critical need for the advancement of novel therapeutic approaches. Key players in the regulation of apoptosis, a fundamental process in cell death, are the B-cell lymphoma 2 (Bcl-2) family proteins, namely Bcl-2 and Bax. These proteins have garnered attention as highly promising targets for the treatment of breast cancer. Targeting the overexpressed anti-apoptotic Bcl-2 protein in breast cancer, Gefitinib (GEF), an EGFR (Epidermal Growth Factor Receptor) inhibitor, emerges as a potential solution. This study focuses on designing Gefitinib-loaded polymeric mixed micelles (GPMM) using poloxamer 407 and TPGS (D-alpha tocopherol PEG1000 succinate) for breast cancer therapy. In silico analyses unveil strong interactions between GEF- Bcl-2 and TPGS-Pgp-2 receptors, indicating efficacy against breast cancer. Molecular dynamics simulations offer insights into GEF and TPGS interactions within the micelles. Formulation optimization via Design of Experiment ensures particle size and entrapment efficiency within acceptable ranges. Characterization tools such as zeta sizer, ATR-FTIR, XRD, TEM, AFM, NMR, TGA, and DSC confirms particle size, structure, functional groups, and thermodynamic events. The optimized micelles exhibit a particle size of 22.34 ± 0.18 nm, PDI of 0.038 ± 0.009, and zeta potential of -0.772 ± 0.12 mV. HPLC determines 95.67 ± 0.34% entrapment efficiency and 1.05 ± 0.12% drug loading capacity. In-vitro studies with MDA-MB-231 cell lines demonstrate enhanced cytotoxicity of GPMM compared to free GEF, suggesting its potential in breast cancer therapy. Cell cycle analysis reveals apoptosis induction through key apoptotic proteins. Western blot results confirm GPMM's ability to trigger apoptosis in MDA-MB-231 cells by activating caspase-3, Bax, Bcl-2, and Parp. In conclusion, these polymeric mixed micelles show promise in selectively targeting cancer cells, warranting future in-vivo studies for optimized clinical application against breast cancer.

Preparation and Characterization of Theophylline Controlled Release Matrix System Incorporating Poloxamer 407, Stearyl Alcohol, and Hydroxypropyl Methylcellulose: A Novel Formulation and Development Study.

BACKGROUND: Theophylline (THN), a bronchodilator with potential applications in emerging conditions like COVID-19, requires a controlled-release delivery system due to its narrow therapeutic range and short half-life. This need is particularly crucial as some existing formulations demonstrate impaired functionality. This study aims to develop a new 12-h controlled-release matrix system (CRMS) in the form of a capsule to optimize dosing intervals. METHODS: CRMSs were developed using varying proportions of poloxamer 407 (P-407), stearyl alcohol (STA), and hydroxypropyl methylcellulose (HPMC) through the fusion technique. Their in vitro dissolution profiles were then compared with an FDA-approved THN drug across different pH media. The candidate formulation underwent characterization using X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. Additionally, a comprehensive stability study was conducted. RESULTS: In vitro studies showed that adjusting the concentrations of excipients effectively controlled drug release. Notably, the CRMS formulation 15 (CRMS-F15), which was composed of 30% P-407, 30% STA, and 10% HPMC, closely matched the 12 h controlled-release profile of an FDA-approved drug across various pH media. Characterization techniques verified the successful dispersion of the drug within the matrix. Furthermore, CRMS-F15 maintained a consistent controlled drug release and demonstrated stability under a range of storage conditions. CONCLUSIONS: The newly developed CRMS-F15 achieved a 12 h controlled release, comparable to its FDA-approved counterpart.

Development and Characterization of Sulfasalazine Cubosomes for Potential Transdermal Drug Delivery.

BACKGROUND: Rheumatoid arthritis is indeed a constant, progressive autoimmune disease that acts on the synovial membrane, distinguished by joint pain, swelling, and tenderness. Sulfasala- zine belongs to BCS Class IV having low solubility and low permeability. To overcome the issue and provide a localized effect Cubosomes were chosen for the transdermal drug delivery system. OBJECTIVE: The primary objective of this investigation was to pass on sulfasalazine-loaded cubo- somes over the skin to treat rheumatoid arthritis. On the way to overcome this issue of oral sulfasala- zine and provide localized effect, Cubosomes were chosen for the transdermal drug delivery system. METHODS: Sulfasalazine-loaded cubosomes were prepared by the top-down method using GMO and Poloxamer 407. Different concentrations of lipid and surfactant were used in the formulation using 32 full factorial designs. The prepared formulations were assessed for p.s, z,p, %EE, FTIR, SEM, in- vitro release, ex-vivo permeation, and deposition studies with pH 7.4 phosphate buffer saline. RESULTS: The particle size varies between 65 nm to 129 nm, while the negative zeta potential ranged from - 18.8 mV to -24.8 mV. The entrapment efficiency was between 87% and 95%. The formulations' in-vitro drug release was carried out for 12 hours. The optimized formulation showed a controlled release of sul- fasalazine and better ex-vivo permeation and deposition properties than sulfasalazine suspension. CONCLUSION: Overall study findings support the possibility of applying transdermal sulfasalazine- loaded cubosomes to alleviate rheumatoid arthritis.

A heparin-based nanogel system for redox and pH dual-responsive delivery of cisplatin.

Heparin recently has been discovered as a novel anti-cancer agent. The combinations of heparin with other agents was reported not only to reduce the undesired effects of free heparin and increase the cellular uptake of the delivered molecules, but also is the basis for the design and development of multi-stimulation response systems to improve their killing cancer cell efficiency at the target positions. This study aimed to design a redox and pH dual-responsive anticancer system based on heparin for cisplatin (CPT) therapy. Heparin was first cross-linked with Poloxamer 407 chains via disulfide bridges to form a redox-sensitive system Hep-P407. CPT was then encapsulated into the Hep-P407 system via the complex of Platin and carboxyl groups to form the redox/pH-responsive system CPT@Hep-P407. The obtained Hep-P407 systems were proved and characterized using specific techniques including1H-NMR, zeta potential, Dynamic Light Scattering (DLS) and Fourier-transform infrared spectroscopy. The dual-responsive behavior to redox and pH of CPT@Hep-P407 was proved through DLS, zeta andin vitrorelease analysis meanwhile its cytotoxicity was investigated using Resazurin assay. The CPT@Hep-P407 system is expected to be a promising redox/pH-responsive anticancer system based on heparin for CPT therapy.

Sustained release polymer and surfactant based solid dispersion of andrographolide exhibited improved solubility, dissolution, pharmacokinetics, and pharmacological activity.

Andrographolide (AD) is a potent natural product with a wide range of pharmacological activities. However, it has low oral bioavailability due to poor solubility and dissolution rate. Solid dispersion (SD) is a promising technique to improve the solubility and dissolution rate of such molecules. In this study, SD formulation of AD was prepared using Kollidon-SR (KSR) and Poloxamer-407 (P-407) as carriers. SD was prepared using the solvent evaporation method and evaluated for the modulation of solubility of AD. The developed SD formulation was characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Further, dissolution rate, yield, drug content, stability, flowability, and pharmacokinetic profile of SD were evaluated. The compatibility of SD with the Caco-2 cells and its impact on the P-glycoprotein (P-gp) mediated efflux was also investigated. Furthermore, carrageenan-induced paw edema, and adjuvant-induced arthritic model were used to evaluate the efficacy of SD. The results showed that SD3 (AD + KSR + P-407, 1:6:8) exhibited the highest solubility and dissolution rate, and significantly improved pharmacokinetic profile compared to native AD. SD3 was found to be stable during storage and displayed excellent yield, drug content, and flowability. This formulation was found to be compatible with the Caco-2 cells and retarded the efflux of P-gp substrate. SD3 also demonstrated substantially better efficacy than native AD in terms of paw edema inhibition (carrageenan-induced paw edema, Wistar rats), and overall improvement of disease condition (in terms of paw edema, arthritic score, AST, ALT, cytokines, radiological changes, and histopathology) in arthritic Wistar rats. In conclusion, SD3 exhibited improved solubility, dissolution rate, pharmacokinetic profile, and pharmacological activity than native AD.