Preparation of Tamsulosin Hydrochloride-Loaded Mucoadhesive In Situ Gelling Polymeric Formulation for Nasal Delivery in Geriatrics.

This study aimed to prepare tamsulosin hydrochloride (HCl)-loaded in situ gelling formulation by using hydroxypropyl methylcellulose (HPMC), gellan gum, poloxamer 188, and benzalkonium chloride. Physicochemical evaluation of formulations included determination of pH, viscosity, gelation time, gel strength, drug content, and sterility. In silico study was performed to analyze interactions between polymers, drug, and mucin glycoprotein. In vitro degradation time, drug release, ex vivo mucoadhesion time, permeation, in vivo pharmacokinetics, and stability studies were performed to assess the formulation. Formulations were transparent and displayed acceptable physicochemical attributes. Tamsulosin HCl and polymers interacted via non-covalent interactions. HPMC formed hydrogen bonds, hydrophobic and van der Waals interactions with mucin protein while the drug formed hydrogen bonds only. Gel formulation degraded in simulated nasal fluid within 24 h. In situ gelling formulation showed 83.8 ± 1.7% drug release and remained adhered to the mucosa for 24.5 ± 1 h. A higher (~ 1.85 times) drug permeation was recorded through mucosa within 6 h by in situ gelling formulation when compared to control counterparts (aqueous solution of drug and in situ gelling formulation without poloxamer 188). Nasal administration of tamsulosin HCl by using in situ gelling formulation led to a ~ 3.3 and ~ 3.5 times, respectively, higher Cmax (maximum plasma concentration) and AUCtotal (total area under the curve) than the orally administered aqueous solution. Relative bioavailability of drug delivered by nasal in situ gelling formulation was 3.5 times the oral counterpart. These results indicated that the prepared in situ gelling formulation can act as a promising candidate for systemic administration of tamsulosin HCl.

Development of In Situ Intranasal System Based on Chitosan Formate.

We studied the potential of using a salt form of chitosan as a pH-sensitive in situ matrix. Among common chitosan salts obtained by heterogeneous synthesis, chitosan formate exhibiting the highest pH-sensitivity was selected. However, the low mucoadhesion strength of the composition, as well as high pH required for the phase transition necessitate designing a polycomponent compound with a poloxamer to additionally provide a thermosensitive phase transition. Compared with the use of pure poloxamer, the chitosan complex demonstrated improved mucoadhesion in in vitro studies, and the phase transition parameters were optimal for intranasal administration. An in vivo study revealed no locally irritating effect of the composition, which allows its further development.

In Situ Gelling Electrospun Ocular Films Sustain the Intraocular Pressure-Lowering Effect of Timolol Maleate: In Vitro, Ex Vivo, and Pharmacodynamic Assessment.

Most common intraocular pressure (IOP) reduction regimens for the management of glaucoma include the topical use of eye drops, a dosage form that is associated with short residence time at the site of action, increased dosing frequency, and reduced patient compliance. In situ gelling nanofiber films comprising poly(vinyl alcohol) and Poloxamer 407 were fabricated via electrospinning for the ocular delivery of timolol maleate (TM), aiming to sustain the IOP-lowering effect of the ß-blocker, compared to conventional eye drops. The electrospinning process was optimized, and the physicochemical properties of the developed formulations were thoroughly investigated. The fiber diameters of the drug-loaded films ranged between 123 and 145 nm and the drug content between 5.85 and 7.83% w/w. Total in vitro drug release from the ocular films was attained within 15 min following first-order kinetics, showing higher apparent permeability (Papp) values across porcine corneas compared to the drug's solution. The fabricated films did not induce any ocular irritation as evidenced by both the hen's egg test on chorioallantoic membrane and the in vivo Draize test. In vivo administration of the ocular films in rabbits induced a faster onset of action and a sustained IOP-lowering effect up to 24 h compared to TM solution, suggesting that the proposed ocular films are promising systems for the sustained topical delivery of TM.

A Lipid-Based In Situ-Forming Hexagonal Phase for Prolonged Retention and Drug Release in the Breast Tissue.

In this study, the addition of monoolein to phosphatidylcholine (PC), tricaprylin, and propylene glycol (PG) mixtures was studied to produce fluid precursor formulations (FIPs) that could transform into hexagonal phase (resistant to aqueous dilution) in vitro and in vivo. The overall goal was to obtain FIPs that could incorporate chemopreventive drugs for subcutaneous administration in the mammary tissue to inhibit the development and/or recurrence of breast cancer. Increasing PG content reduced FIP viscosity up to ~ 2.5-fold, while increases in PC (over monoolein) increased the formation of emulsified systems. The hexagonal phase was observed at 20% of water and higher, with the minimum amount of water necessary for this formation increasing with PG content. The selected FIP formed a depot in vivo after ~ 24 h of administration; its structure was compatible with the hexagonal phase and it remained in the mammary tissue for at least 30 days, prolonging the permanence of a fluorescent probe. In vitro, the release of the synthetic retinoid fenretinide was slow, with ~ 9% of the drug released in 72 h. Consistent with this slow release, fenretinide IC50 in breast cancer cells was ~ 100-fold higher in the selected FIP compared to its solution. The FIP reduced cell migration and presented higher cytotoxicity towards tumor compared to non-tumor cells. Given the limited number of options for pharmacological prevention of breast cancer development and recurrences, this formulation could potentially find applicability to reduce the frequency of administration and improve local concentrations of chemopreventive drugs.

Microemulsion for Prolonged Release of Fenretinide in the Mammary Tissue and Prevention of Breast Cancer Development.

The need of pharmacological strategies to preclude breast cancer development motivated us to develop a non-aqueous microemulsion (ME) capable of forming a depot after administration in the mammary tissue and uptake of interstitial fluids for prolonged release of the retinoid fenretinide. The selected ME was composed of phosphatidylcholine/tricaprylin/propylene glycol (45:5:50, w/w/w) and presented a droplet diameter of 175.3 ± 8.9 nm. Upon water uptake, the ME transformed successively into a lamellar phase, gel, and a lamellar phase-containing emulsion in vitro as the water content increased and released 30% of fenretinide in vitro after 9 days. Consistent with the slow release, the ME formed a depot in cell cultures and increased fenretinide IC50 values by 68.3- and 13.2-fold in MCF-7 and T-47D cells compared to a solution, respectively. At non-cytotoxic concentrations, the ME reduced T-47D cell migration by 75.9% and spheroid growth, resulting in ∼30% smaller structures. The depot formed in vivo prolonged a fluorochrome release for 30 days without producing any sings of local irritation. In a preclinical model of chemically induced carcinogenesis, ME administration every 3 weeks for 3 months significantly reduced (4.7-fold) the incidence of breast tumors and increased type II collagen expression, which might contribute to limit spreading. These promising results support the potential ME applicability as a preventive therapy of breast cancer.

Implementation and in vitro characterization of calcium-free in situ gelling oral reconstituted suspension for potential overweight treatment.

In this work, oral granules that were easily dissolved in aqueous dispersion, were prepared. These oral suspensions were formulated with sodium alginate (AlgNa), chitosan (CHI) and sodium carboxymethylcellulose (CMC Na). The gels were formulated by pouring the suspensions into 150 ml of simulated gastric fluid (SGF) pH 1.2 at 37° C. The in-situ gelling mechanism was based on the ionization states of the three biopolymers as a function of the pH of the medium. Fourier transform infrared analysis of gels confirmed the interactions between alginate and chitosan. According to the scanning electron microscopy analysis, the gels were characterized by a firm and homogeneous structure. The obtained values of the elastic storage modulus, G', varied between 10 1 and 10 7 Pa. The eliminated volume of the unabsorbed liquid by the gels fluctuated between 25% and 55% of the total liquid volume. The quality of the gels was improved when a maximum concentration of alginate ( 4 g / 100 ml ) , a minimum concentration of chitosan ( 0.5 g / 100 ml ) and a maximum amount of carboxymethylcellulose ( 4 g / 100 ml ) were used. The value of their elastic modulus, G' was around 10 5 Pa and the residual unabsorbed volume of the liquid was 25% of the total liquid volume. According to the obtained results, the prepared gels could induce a feeling of fullness by stimulating the gastric distension and they could potentially be applied as anti-obesity medication.

Overview of in situ gelling injectable hydrogels for diabetic wounds.

Diabetes mellitus (DM) is an endocrine disorder that causes increased blood glucose than usual due to insulin impairment. In DM, several complications arise in which diabetic wound (DW) is the most devastating complication. About 25% of patients with DM expected to develop DWs in their lifetime and undergo limb amputations. Even though several treatments such as surgery, debridement, wound dressings, advanced therapies were available, the overall conclusion has been that with very few exceptions, patients still suffer from limitations like pain, frequent dress changing, high rates of failure, and cost involvement. Further, the treatments involving the delivery of therapeutic agents in treating DWs have limited success due to abnormal levels of proteases in the DW environment. In this backdrop, in situ gelling injectable hydrogels have gained special attention due to their easy encapsulation of therapeutic medications and prolonged release, filling the wound defect areas, ease of handling, and minimally invasive surgical procedures. Though the in situ gelling injectable hydrogels are developed a couple of decades ago, their use for treating DW has not yet been explored thoroughly. Thus, in this review, we have covered the sequential events of DW healing, pathophysiology, current treatments, and its limitations, along with a particular emphasis on the mechanism of action of these in situ gelling injectable hydrogels treating DWs.

In Situ Gelling Systems Using Pluronic F127 Enhance Corneal Permeability of Indomethacin Nanocrystals.

We previously designed an ophthalmic dispersion containing indomethacin nanocrystals (IMC-NCs), showing that multiple energy-dependent endocytoses led to the enhanced absorption of drugs from ocular dosage forms. In this study, we attempted to prepare Pluronic F-127 (PLF-127)-based in situ gel (ISG) incorporating IMC-NCs, and we investigated whether the instillation of the newly developed ISG incorporating IMC-NCs prolonged the precorneal resident time of the drug and improved ocular bioavailability. The IMC-NC-incorporating ISG was prepared using the bead-mill method and PLF-127, which yielded a mean particle size of 50-150 nm. The viscosity of the IMC-NC-incorporating ISG was higher at 37 °C than at 10 °C, and the diffusion and release of IMC-NCs in the IMC-NC-incorporating ISG were decreased by PLF-127 at 37 °C. In experiments using rabbits, the retention time of IMC levels in the lacrimal fluid was enhanced with PLF-127 in the IMC-NC-incorporating ISG, whereby the IMC-NC-incorporating ISG with 5% and 10% PLF-127 increased the transcorneal penetration of the IMCs. In contrast to the results with optimal PLF-127 (5% and 10%), excessive PLF-127 (15%) decreased the uptake of IMC-NCs after instillation. In conclusion, we found that IMC-NC-incorporating ISG with an optimal amount of PLF-127 (5-10%) resulted in higher IMC corneal permeation after instillation than that with excessive PLF-127, probably because of the balance between higher residence time and faster diffusion of IMC-NCs on the ocular surface. These findings provide significant information for developing ophthalmic nanomedicines.

Patient-Friendly, Olfactory-Targeted, Stimuli-Responsive Hydrogels for Cerebral Degenerative Disorders Ensured > 400% Brain Targeting Efficiency in Rats.

Non-invasive brain therapy for chronic neurological disorders is in high demand. Vinpocetine (VIN) tablets for cerebrovascular degenerative disorders ensued < 7% oral bioavailability. The olfactory pathway (providing direct brain access) can improve VIN pharmacokinetic/pharmacodynamic profile. In this context, VIN hydrogels based on temperature-, pH-, and ion-triggered gelation in physiological milieu were formulated. Poloxamer-chitosan (PLX-CS) and carbopol-HPMC-alginate (CP-HPMC-SA) systems were optimized for appropriate gelation time, temperature, and pH. PLX-CS-hydrogels exhibited strong mucoadhesion for > 8 h, while CP-HPMC-SA hydrogels were mucoadhesive in simulated nasal fluid, owing to pH and ion-activated gelation. Along with prolonged mucosal residence, hydrogels confirmed sustained VIN release (> 24 h), especially from CP-HPMC-SA hydrogels. As proof of concept, brain exposure of intranasal VIN hydrogels was investigated in rats versus VIN-IV bolus. PLX-CS provided 146% increase in AUC0-30 and 3-fold maximum brain concentration (BCmax) relative to IV bolus. BCmax was reached after 4 h versus 1 h (IV bolus). CP-HPMC-SA hydrogel showed superior brain targeting efficiency (460%) and brain direct transport percentage (78.23%). VIN plasma pharmacokinetics confirmed 45-60% reduction in AUCplasma versus IV bolus, while PCmax of CP-HPMC-SA and PLX-CS represented 17 and 28% that of IV bolus, respectively. Olfactory-targeted hydrogels grant effective, sustainable VIN brain level with minimal systemic exposure, thus, assuring lower dose, dose frequency, side effects, and per se better patient compliance.

Brinzolamide Dimethyl Sulfoxide In Situ Gelling Ophthalmic Solution: Formulation Optimisation and In Vitro and In Vivo Evaluation.

In the present work, a cost-effective, stable and sustained release ophthalmic solution formulation of brinzolamide (BRZ) was developed for the treatment of glaucoma. The prototype formulation undergoes 'in situ gelling' when administered in the eye, thereby providing longer residence (16-24 h). As a result, the same therapeutic endpoint is achieved with once daily dosing vis-à-vis the commercially available product Azopt® (brinzolamide 1.0% w/v, Alcon Laboratories, USA) that requires 3-4 times instillations per day. The prototype formulations were prepared using dimethyl sulfoxide, polyoxyl 35 castor oil and polysorbate 80. Gellan gum was used as the in situ gelling agent. Formulation variables like (i) concentration of the drug, dimethyl sulfoxide and in situ gelling agent and (ii) type and concentration of solubiliser showed a significant effect on the solubility of brinzolamide, in vitro gelling time, in vitro drug release and in situ gel stability. Prototype formulations were evaluated in New Zealand white rabbits for ocular toxicity and efficacy study. The tested formulations were well tolerated and reduced intraocular pressure (IOP) from 25-28 to 12-14 mmHg compared to saline and placebo control samples. Additionally, a significant increase in the area under change in IOP from baseline (ΔIOP) vs. time curve and a longer mean residence time (MRT) were also observed for the test formulations (7.4 to 17.7 h) compared to the commercially available suspension of Azopt® (4.9 h) (p < 0.0001). Thus, 'in situ gelling' formulation strategy described in this work can work as a viable option for ocular delivery of brinzolamide for the treatment of glaucoma.

Levofloxacin Hemihydrate In Situ Gelling Ophthalmic Solution: Formulation Optimization and In Vitro and In Vivo Evaluation.

Bacterial conjunctivitis is a leading cause of ocular infections requiring short-term therapeutic treatment with frequent administration of drugs on daily basis. Topical dosage forms available in the market for the treatment of bacterial conjunctivitis such as simple drug solutions and suspensions are rapidly eliminated from the precorneal space upon instillation due to tear turn over and nasolacrimal drainage, limiting intraocular bioavailability of drug to less than 10% of the administered dose. To overcome issues related to conventional drop, an effort was made to design and evaluate prolong release ophthalmic solution of levofloxacin hemihydrate (LFH) using ion-sensitive in situ gelling polymer. Gellan gum was used as the in situ gelling agent. Formulations were screened based on in vitro gelation time, in vitro drug release, and stability towards sol to gel conversion upon storage. The prototype formulations exhibiting quick in vitro gelling time (< 15 s), prolonged in vitro drug release (18-24 h), and stability for at least 6 months at 25°C/40% relative humidity (RH) and 40°C/25% RH were evaluated for pharmacokinetic studies using healthy New Zealand white rabbits. Tested formulations were found to be well-tolerated and showed significant increase in AUC0-24 (22,660.39 h ng/mL) and mean residence time (MRT 12 h) as compared with commercially available solution Levotop PF® (Ajanta Pharma Ltd., India)(AUC0-24 6414.63 h ng/mL and MRT 4 h). Thus, solution formulations containing in situ gelling polymer may serve as improved drug delivery system providing superior therapeutic efficacy and better patient compliance for the treatment of bacterial conjunctivitis.

Clinical Applications of Injectable Biomaterials.

Regenerative medicine is an interdisciplinary field that aims to regenerate the lost or diseased tissues through the combinational use of cells, biomolecules and/or biomaterials. Injectable biomaterials have been comprehensively evaluated for use in this field for their prominent properties, such as ease of handling, providing a better integration of the native tissue by filling irregular defects and having controllable chemical and physical properties. This class of biomaterials can be developed from natural or synthetic origin materials, decellularized matrices or from combinations of materials to form composites. Injectable biomaterials enable minimally invasive approach when compared with traditional open surgeries, which can reduce the cost, and speed up the recovery time for the patients. Cells, growth factors and/or bioactive molecules can be effectively delivered to the target tissue using injectable biomaterials, making them desirable for a number of clinical applications. This chapter gives an overview on injectable biomaterials and their clinical applications in soft, hard, and cardiovascular tissue regeneration.

A novel ion-activated in situ gelling ophthalmic delivery system based on κ-carrageenan for acyclovir.

The aim of this study was to prepare and evaluate ion-activated in situ gel ophthalmic drug delivery system based on κ-carrageenan (KC), using acyclovir as a model drug, hydroxypropyl methylcellulose (HPMC) as the viscosity agent and hydroxypropyl-ß-cyclodextrin (HP-ß-CD) as the penetration enhancer. The two ternary phase diagrams exhibited the effect of K+ and Ca2+ on the sol-to-gel transition, which turned out that KC was more sensitive to K+. The optimal ophthalmic matrix (prepared from KC and HPMC) was optimized with in vitro drug release test. The apparent permeability coefficient of acyclovir under 2% HP-ß-CD was found to have dramatically increased (2.16-ploid) than that of conventional eye drops (p < .05). The ion-activated in situ gel based on KC significantly delayed drug release and its bioavailability could be improved in comparison with the conventional eye drops. Hence, it has the potential to be a novel kind of ocular drug delivery system.

In Situ Gelling Liquid Crystalline System as Local siRNA Delivery System.

An effective short interfering RNA (siRNA) delivery system protects the siRNA from degradation, facilitates its cellular uptake, and promotes its release into the cytoplasm. Local administration of siRNA presents advantages over systemic administration, such as the possibility to use lower doses and allow local and sustained release. In this context, in situ solidifying organogels based on monoglycerides (MO), polyethylenimine (PEI), propylene glycol (PG) and tris buffer are an attractive strategy for intratumoral delivery of siRNA. In this study, precursor fluid formulation (PFF) composed of MO/PEI/PG/tris buffer at 7.85:0.65:76.5:15 (w/w/w/w) was used to deliver siRNA to tumor cells. The internal structure of the gel obtained from PFF was characterized using small angle X-ray scattering (SAXS). In addition, its ability to complex siRNA, protect it from degradation, and functionally deliver it to tumor cells was investigated. Moreover, in vivo gel formation following intratumoral injection was evaluated. The gel formed in excess water from PFF was found to comprise a mixture of hexagonal and cubic phases. The system was able to complex high amounts of siRNA, protect it from degradation, promote siRNA internalization, and induce gene silencing in vitro in a variety of tumor cell lines. Moreover, a gel formed in situ following intratumoral injection in a murine xenograft model. In conclusion, PFF is a potential delivery system for local and sustained delivery of siRNA to tumor tissue after intratumoral administration.

Preparation, characterization and biocompatibility studies of thermoresponsive eyedrops based on the combination of nanostructured lipid carriers (NLC) and the polymer Pluronic F-127 for controlled delivery of ibuprofen.

CONTEXT: Nanostructured lipid carrier (NLC) dispersions present low viscosity and poor mucoadhesive properties, which reduce the pre-corneal residence time and consequently, the bioavailability of ocular drugs. OBJECTIVE: The aim of this study was to prepare thermoresponsive eyedrops based on the combination of lipid nanoparticles and a thermoresponsive polymer with mucomimetic properties (Pluronic® F-127). MATERIALS AND METHODS: NLCi dispersions were prepared based on the melt-emulsification and ultrasonication technique. Physicochemical and morphological characteristics of the colloidal dispersions were evaluated. The formulation was also investigated for potential cytotoxicity in Y-79 human retinoblastoma cells and the in vitro drug release profile of the ibuprofen was determined. RESULTS: NLCi showed a Z-average below 200 nm, a highly positive zeta potential and an efficiency of encapsulation (EE) of ∼90%. The gelification of the NLCi dispersion with 15% (w/w) Pluronic® F-127 did not cause significant changes to the physicochemical properties. The potential NLC-induced cytotoxicity was evaluated by the Alamar Blue reduction assay in Y-79 cells, and no relevant cytotoxicity was observed after exposure to 0-100 µg/mL NLC for up to 72 hours. The optimized formulations showed a sustained release of ibuprofen over several hours. DISCUSSION AND CONCLUSION: The strategy proposed in this work can be successfully used to increase the bioavailability and the therapeutic efficacy of conventional eyedrops.

QbD-Enabled Development of Novel Stimuli-Responsive Gastroretentive Systems of Acyclovir for Improved Patient Compliance and Biopharmaceutical Performance.

The current studies entail systematic quality by design (QbD)-based development of stimuli-responsive gastroretentive drug delivery systems (GRDDS) of acyclovir using polysaccharide blends for attaining controlled drug release profile and improved patient compliance. The patient-centric quality target product profile was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies, carried out through Ishikawa fish bone diagram and failure mode, effect, and criticality analysis, helped in identifying the plausible risks or failure modes affecting the quality attributes of the drug product. A face-centered cubic design was employed for systematic development and optimization of the concentration of sodium alginate (X 1) and gellan (X 2) as the critical material attributes (CMAs) in the stimuli-responsive formulations, which were evaluated for CQAs viz. viscosity, gel strength, onset of floatation, and drug release characteristics. Mathematical modeling was carried out for generation of design space, and optimum formulation was embarked upon, exhibiting formulation characteristics marked by excellent floatation and bioadhesion characteristics along with promising drug release control up to 24 h. Drug-excipient compatibility studies through FTIR and DSC revealed absence of any interaction(s) among the formulation excipients. In vivo pharmacokinetic studies in Wistar rats corroborated extension in the drug absorption profile from the optimized stimuli-responsive GR formulations vis-à-vis the marketed suspension (ZOVIRAX®). Establishment of in vitro/in vivo correlation (IVIVC) revealed a high degree of correlation between the in vitro and in vivo data. In a nutshell, the present investigations report the successful development of stimuli-responsive GRDDS of acyclovir, which can be applicable as a platform approach for other drugs too.

Development and Characterization of Thermosensitive and Bioadhesive Ophthalmic Formulations Containing Flurbiprofen Solid Dispersions.

In this study, we aimed to develop thermosensitive and bioadhesive in situ gelling systems containing solid dispersions of flurbiprofen (FB-SDs) using poloxamer 407 (P407) and 188 (P188) for ophthalmic delivery. FB-SDs were prepared with the melt method using P407, characterized by solubility, stability, SEM, DSC, TGA, and XRD analyses. Various formulations of poloxamer mixtures and FB-SDs were prepared using the cold method and P407/P188 (15/26.5%), which gels between 32 and 35 °C, was selected to develop an ophthalmic in situ gelling system. Bioadhesive polymers Carbopol 934P (CP) or carboxymethyl cellulose (CMC) were added in three concentrations (0.2, 0.4, and 0.6% (w/w)). Gelation temperature and time, mechanical properties, flow properties, and viscosity values were determined. The in vitro release rate, release kinetics, and the release mechanism of flurbiprofen (FB) from the ophthalmic formulations were analyzed. The results showed that FB-SDs' solubility in water increased 332-fold compared with FB. The oscillation study results indicated that increasing bioadhesive polymer concentrations decreased gelation temperature and time, and formulations containing CP gel at lower temperatures and in a shorter time. All formulations except F3 and F4 showed Newtonion flow under non-physiological conditions, while all formulations exhibited non-Newtonion pseudoplastic flow under physiological conditions. Viscosity values increased with an increase in bioadhesive polymer concertation at physiological conditions. Texture profile analysis (TPA) showed that CP-containing formulations had higher hardness, compressibility, and adhesiveness, and the gel structure of formulation F4, containing 0.6% CP, exhibited the greatest hardness, compressibility, and adhesiveness. In vitro drug release studies indicated that CP and CMC had no effect below 0.6% concentration. Kinetic evaluation favored first-order and Hixson-Crowell kinetic models. Release mechanism analysis showed that the n values of the formulations were greater than 1 except for formulation F5, suggesting that FB might be released from the ophthalmic formulations by super case II type diffusion. When all the results of this study are evaluated, the in situ gelling formulations prepared with FB-SDs that contained P407/P188 (15/26.5%) and 0.2% CP or 0.2% CMC or 0.4 CMC% (F2, F5, and F6, respectively) could be promising formulations to prolong precorneal residence time and improve ocular bioavailability of FB.

Preparation, optimization, and characterization of genistein-ginseng long-acting polymeric gel as a breast cancer treatment alternative.

To address the prevalent genistein (GST) metabolism and inadequate intestinal absorption, an oral long-acting and gastric in-situ gelling gel was designed to encapsulate and localize the intestinal release of the loaded genistein-ginseng (GST-GNS) solid dispersion. Because of the high breast perfusion of GST upon oral absorption, the GST-GNS solid dispersion was developed to enhance GST's dissolution and penetration while offering a synergistic impact against breast cancer (BC). Physiochemical analysis of the GST-GNS solid dispersion, release analysis, gel characterizations, storage stability, penetration, and in vitro cytotoxicity studies were carried out. GST-GNS solid dispersion showed improved dissolution and penetration as compared to raw GST. GST-GNS solid dispersion homogenous shape particles and hydrophilic contacts were revealed by scanning electron microscopy and Fourier Transform-Infrared analysis, respectively. GST-GNS solid dispersion's diffractogram shows the amorphous character. A second modification involved creating a gastric in-situ gelling system loaded with GST-GNS solid dispersion. This system demonstrated improved GST penetration employing the solid dispersion, as well as the localizing of the GST release at the intestinal media and antitumor synergism against BC. For a better therapeutic approach for BC, the innovative oral GST long-acting gel encasing the GST-GNS solid dispersion would be recommended.

Hyaluronate loaded advanced wound dressing in form of in situ forming hydrogel powders: Formulation, characterization, and therapeutic potential.

In this paper, a blend composed of alginate-pectin-chitosan loaded with sodium hyaluronate in the form of an in situ forming dressing was successfully developed for wound repair applications. This complex polymeric blend has been efficiently used to encapsulate hyaluronate, forming an adhesive, flexible, and non-occlusive hydrogel able to uptake to 15 times its weight in wound fluid, and being removed without trauma from the wound site. Calorimetric and FT-IR studies confirmed chemical interactions between hyaluronate and polysaccharides blend, primarily related to the formation of a polyelectrolytic complex between hyaluronate and chitosan. In vivo wound healing assays on murine models highlighted the ability of the loaded hydrogels to significantly accelerate wound healing compared to a hyaluronic-loaded ointment. This was evident through complete wound closure in <10 days, accompanied by fully restored epidermal functionality and no indications of the site of excision or treatment. Therefore, all these results suggest that hyaluronate-loaded powders could be a very promising conformable dressing in several wound healing applications where exudate is present.

An In Situ-Gelling Conductive Hydrogel for Potential Use in Neural Tissue Engineering.

Cerebral cavitation is usual following acute brain injuries, such as stroke and traumatic brain injuries, as well as after tumor resection. Minimally invasive implantation of an injectable scaffold in the cavity is a promising approach for potential regeneration of tissue loss. This study aimed at designing an in situ-gelling conductive hydrogel containing silk fibroin (SF), brain decellularized extracellular matrix (dECM), and carbon nanotubes (CNT) for potential use in brain tissue regeneration. Two percent w/v SF hydrogels with different concentrations of dECM (0.1%, 0.2%, or 0.3% w/v) and CNTs (0.05%, 0.1%, or 0.25% w/v) were fabricated and characterized. It was observed that with the addition of dECM, the porosity decreased, whereas swelling and electrical conductivity tended to increase. The addition of dECM also led to a faster resorption rate, but no significant change in compressive modulus. Addition of CNTs, on the other hand, led to a denser, stronger, and more regular porous structure, higher swelling ratio, faster gelation time, slower degradation rate, and a significant increase in electrical conductivity. dECM and CNTs combined together resulted in superior porosity, swelling, resorption rate, mechanical properties, and electrical conductivity compared with SF scaffolds containing only dECM or CNTs. Hydrogel samples containing 2% SF, 0.3% dECM, and 0.1% CNTs had a high porosity (58.9%), low swelling ratio (15.9%), high conductivity (2.35 × 10-4 S/m), and moderate degradation rate (37.3% after 21 days), appropriate for neural tissue engineering applications. Cell evaluation studies also showed that the hydrogel systems support the cell adhesion and growth, with no sign of significant cytotoxicity. Impact statement Tissue loss and formation of a fluid-filled cavity following stroke, traumatic brain injury, or brain tumor resection lead to sensorimotor and/or cognitive deficits. The lack of a healthy extracellular matrix in the cavity avoids the endogenous cell migration and axonal sprouting and may also worsen the secondary injuries to peri-lesional tissue. Due to the brain anatomy, simple implantation of tissue engineering scaffolds to the injured site is not possible in many cases. Therefore, the development of injectable scaffolds that support neural growth and differentiation is crucial for tissue repair or limiting the expansion of damage region.