Local Sustained Dinutuximab Delivery and Release From Methacrylated Chondroitin Sulfate.

Neuroblastoma (NB) is the most common pediatric extracranial solid tumor. High-risk NB is a subset of the disease that has poor prognosis and requires multimodal treatment regimens, with a 50% rate of recurrence despite intervention. There is a need for improved treatment strategies to reduce high-risk patient mortality. Dinutuximab is an anti-GD2 antibody ideal for targeting GD2 expressing NB cells, but binding of the antibody to peripheral nerve fibers leads to severe pain during systemic administration. Intratumoral delivery of the anti-GD2 antibody would allow for increased local antibody concentration, without increasing systemic toxicity. Chondroitin Sulfate (CS) is a biocompatible glycosaminoglycan that can be methacrylated to form CSMA, a photocrosslinkable hydrogel that can be loaded with therapeutic agents. The methacrylation reaction time can be varied to achieve different degrees of substitution, resulting in different release and degradation profiles. In this work, 4 and 24 h reacted CSMA was used to create hydrogels at 10% and 20% CSMA. Sustained in vitro release of dinutuximab from these formulations was observed over a 24-day period, and 4 h reacted 10% CSMA hydrogels had the highest overall dinutuximab release over time. An orthotropic mouse model was used to evaluate in vivo response to dinutuximab loaded 4 h methacrylated 10% CSMA hydrogels as compared to bolus tail vein injections. Tumor growth was monitored, and there was a statistically significant increase in the days to reach specific tumor size for tumors treated with intratumoral dinutuximab-loaded hydrogel compared to those treated with dinutuximab solution through tail vein injection. This supports the concept that locally delivering dinutuximab within the hydrogel formulation slowed tumor growth. The CSMA hydrogel-only treatment slowed tumor growth as well, an interesting effect that may indicate interactions between the CSMA and cell adhesion molecules in the tumor microenvironment. These findings demonstrate a potential avenue for local sustained delivery of dinutuximab for improved anti-tumoral response in high-risk NB.

Role of EYP-1901 in neovascular age-related macular degeneration and diabetic eye diseases: review of Phase I/II trials.

EYP-1901 (Duravyu) has demonstrated promising outcomes in Phases I and II clinical trials for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)/diabetic retinopathy. This innovative treatment capitalizes on the potent anti-angiogenic properties of vorolanib, an inhibitor that targets all isoforms of VEGF, effectively mitigating the pathological neovascularization and vascular permeability that underpin these retinal conditions. EYP-1901 is integrated with the Durasert drug delivery system to administer a sustained release of vorolanib directly to the posterior segment of the eye. This delivery system ensures a consistent therapeutic effect over an extended period and significantly reduces the frequency of clinical interventions required, offering a more convenient treatment regimen while maintaining patient safety.

Neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR) are eye problems that can make you lose your sight. These eye problems happen when blood vessels in the eye do not work right. Right now, people need lots of shots in their eyes to treat it. EYP-1901 (Duravyu) is a new medicine that helps people with fewer shots in their eyes. It has two parts: one that helps the medicine last longer, and another that helps stop the problem in the eye. Early tests show it works well and helps people keep their sight with fewer treatments.

Sustainable release artifact in PLGA microspheres for prolonged local aesthetics in postoperative pain management.

The challenge of effectively managing long-term pain after surgery remains a significant issue in clinical settings. Although local anesthetics are preferred for their effective pain relief and few side effects, their short-lasting effect does not fully meet the pain relief needs after surgery. Articaine, widely used for postoperative pain relief as a local anesthetic, is pharmacologically limited by its short half-life, which reduces the duration of its pain-relieving effects. To overcome this issue, this study presents a new approach using poly (lactic-co-glycolic acid) (PLGA) microspheres for controlled articaine release, aiming to extend its analgesic effect while reducing potential toxicity. The PLGA microspheres were shown to extend the release of articaine for at least 72 h in lab tests, displaying excellent biocompatibility and low toxicity. When used in a rodent model for postoperative pain, the microspheres provided significantly prolonged pain relief, effectively reducing pain for up to 3 days post-surgery, without causing inflammation or tissue damage for over 72 h after being administered. The extended release and high safety profile of these PLGA microspheres highlight their promise as a new method for delivering local anesthetics, opening up new possibilities for pain management in the future.

Fabrication, characterization and simulated gastrointestinal digestion of sea buckthorn pulp oil microcapsule: effect of wall material and interfacial bilayer stabilization.

BACKGROUND: Sea buckthorn (Hippophae rhamnoides L.) pulp oil is rich in functional components; however, low water solubility and stability limit its applications. This study fabricated sea buckthorn pulp oil microcapsules using whey protein isolate (WPI), soy protein isolate (SPI), sodium caseinate (NaCN), gum arabic (GA), starch sodium octenylsuccinate (OSAS) and SPI mixed with chitosan (CHI). The influences of these wall materials on physicochemical properties, release behavior and digestibility were explored. RESULTS: Protein-based wall materials (WPI, NaCN, SPI) demonstrated lower bulk densities due to their porous structures and larger particle sizes, while GA and OSAS produced denser microcapsules. Encapsulation efficiency was the highest for protein-based microcapsules (79.41-89.12%) and the lowest for GA and OSAS. The surface oil percentage of protein-based microcapsules (1.41-4.40%) was lower than that of the other microcapsules. Protein-based microcapsules showed concave and cracked surfaces, while GA and OSAS microcapsules were spherical and smooth. CHI improved reconstitution performance, leading to faster dissolution. During simulated gastrointestinal digestion, protein-based microcapsules released more free fatty acids (FFAs) in the intestinal phase, while CHI-modified SPI microcapsules showed a delayed release pattern due to thicker walls. CONCLUSION: Protein-based wall materials were more effective for sea buckthorn pulp oil microencapsulation, providing higher encapsulation efficiency, better flow properties and releasing more FFAs. The addition of CHI led to the layer-by-layer self-assembly of the microcapsule wall and resulted in sustained release during in vitro intestinal digestion. These findings suggested the potential of protein-based microcapsules for targeted delivery and improved applications of bioactive oils in the food industry. © 2024 Society of Chemical Industry. Published by John Wiley & Sons Ltd.

Preparation and characterization of ovomucin self-assembly nanoparticles under glycerol compression for astaxanthin delivery: Sustained release and antioxidant activity.

Astaxanthin (AST) is a natural hydrophobic nutrient with various biological activities, but its low solubility limits its application. In this study, self-assembly nanoparticles were prepared by ovomucin (OVM) and Ca2+ with the enhancement of glycerol to deliver AST. Glycerol compressed the particle size of nanoparticles from 175.7 ± 1.8 to 142.9 ± 0.6 nm, and the nanoparticles had a strong negative charge (-28.9 ± 0.6 mV). Ultraviolet-visible spectroscopy and X-ray diffraction (XRD) confirmed the successful encapsulation of AST in an amorphous form with a high encapsulation efficiency (82.9% ± 2.1%). Fourier transform infrared and circular dichroism analyses demonstrated that nanoparticles formation mainly involved electrostatic interactions and hydrophobic interactions. AST in nanoparticles presented excellent gastric juice resistance and sustained release ability, whereas free radical scavenging efficiency reached up to 75%. In addition, the nanoparticles had no apparent toxicity to cell viability. This study is expected to provide a new insight into the safe and efficient delivery of AST, while demonstrating the potential of OVM as a delivery carrier in the food and health industries.

Blood Clots Used as Natural Biomaterials for Antibiotic Delivery in Vitro.

INTRODUCTION: The search for an optimal drug delivery system capable of addressing a wide range of wounds and defects in regenerative medicine remains a challenge. Blood clots (BCs) have been implicated as a promising candidate due to their natural occurrence, autologous nature, and potential for tissue repair. The aim of this study is to investigate BC as a vehicle for antibiotic delivery and its effectiveness in infection control. METHODS: BCs derived from murine and porcine models were used to study the in vitro release of gentamicin and vancomycin over a 7-d period. Moreover, BCs conjugated with mesenchymal stem cells and these antibiotics were assessed for antimicrobial activity via microdilution and agar well diffusion, and quantification of vascular endothelial growth factor release through enzyme-linked immunosorbent assay. RESULTS: Conjugated BCs maintained a sustained release of gentamicin and vancomycin throughout the 7-d period. Functional tests confirmed antimicrobial activity with zones of inhibition comparable to antibiotic controls. Vascular endothelial growth factor quantification revealed a pronounced and sustained release, especially from BCs conjugated with male mesenchymal stem cells, suggesting a gender influence on therapeutic outcomes. This sex-specific variance underscores the need for tailored therapeutic approaches in regenerative medicine applications. CONCLUSIONS: We demonstrated the remarkable potential of BC as a drug delivery system through sustained antibiotic and growth factor release, both of which are key in preventing infection and promoting tissue regeneration. The ease and cost effectiveness of BC preparation as well as its favorable federal regulatory profile support the potential translational application of BCs as a natural biomaterial in regenerative medicine.

Microneedles with Implantable Tip-Accumulated Therapeutics for the Long-Term Management of Psoriasis.

Methotrexate is successfully used as the gold standard for managing moderate-to-severe psoriasis. However, the low bioavailability and short half-life of the oral pills and the invasiveness of the parenteral injections make these suboptimal therapeutic options. Microneedles, bridging the advantages of the former forms, are successfully used to deliver methotrexate for different therapeutic purposes. However, the utilized dissolving microneedles demand frequent administration, potentially compromising patients' compliance. Additionally, the high toxicity of methotrexate prompts a quest for safer alternatives. Phloretin, a natural compound with confirmed antipsoriatic potential, emerges as a promising candidate. Herein, microneedle patches with separable, slow-degrading tips are developed for the sustained delivery of methotrexate and phloretin, as a comprehensive solution for long-term psoriasis management. Both compounds are individually loaded at varying doses and display sustained-release profiles. The developed microneedle patches demonstrate high mechanical strength, favorable drug delivery efficiency, and remarkable antipsoriatic potential both in vitro in keratinocytes and in vivo in a psoriasis mouse model. Comparative analysis with two subcutaneous injections reveals a similar antipsoriatic efficacy with a single patch of either compound, with prominent phloretin safety. Therefore, the developed patches present a superior alternative to methotrexate's current marketed forms and provide a viable alternative (phloretin) with comparable antipsoriatic efficacy and higher safety.

Fibroblast Growth Factor Receptor 1-Specific Dehydrogelation to Release Its Inhibitor for Enhanced Lung Tumor Therapy.

Fibroblast growth factor receptor 1 (FGFR1) is emerging as a promising molecular target of lung cancer, and various FGFR1 inhibitors have exhibited significant therapeutic effects on lung cancer in preclinical research. Due to their low targeting ability or bioavailability, direct administration of these inhibitors may cause side effects. Herein, a hydrogelator, Nap-Phe-Phe-Phe-Glu-Thr-Glu-Leu-Tyr-OH (Nap-Y), was rationally designed to coassemble with an FGFR1 inhibitor nintedanib (Nin) to form a peptide hydrogel Gel Y/Nin for localized administration and FGFR1-triggered release of Nin. Upon specific phosphorylation by FGFR1 overexpressed on lung cancer cells, Nap-Y in Gel Y/Nin is converted to the hydrophilic product Nap-Phe-Phe-Phe-Glu-Thr-Glu-Leu-Tyr(H2PO3)-OH (Nap-Yp), leading to dehydrogelation of the gel and subsequent Nin release. In vitro experiments demonstrate that the release of Nin in a sustained manner from Gel Y/Nin significantly suppresses the survival, migration, and invasion of A549 cells by inhibiting FGFR1 expression and its phosphorylation function on downstream signaling molecules. Nude mouse studies show that Gel Y/Nin exhibits enhanced therapeutic efficacy on lung tumor than free Nin. We anticipate that Gel Y/Nin will be utilized for lung cancer treatment in clinical settings in the near future.

A novel multifunctional PEEK internal fixation plate regulated by Gentamicin/chitosan coating.

Polyetheretherketone (PEEK) has been broadly used in orthopedic implant devices. Nevertheless, the bioinert tended to cause implant loosening and bacterial infection in orthopedic and trauma surgery. In this study, a drug-laden chitosan coating (CS) was constructed and deposited on the porous surface of PEEK (CG-SPEEK) internal fixation plate for multi-functionalization. The physical characterizations of CG-SPEEK were further investigated in the morphology, hydrophilicity, surface energy, roughness, drug release and mechanical properties. CG-SPEEK exhibited excellent antibacterial capabilities in both Staphylococcus aureus and Escherichia coli compared to other groups. Besides, BMSCs cells showed better biocompatibility and certain osteogenic activity on composite coating in vitro. Furthermore, CG-SPEEK promoted bone regeneration to some extent and express certain effect against infections in vivo study. Overall, combining personalized design and modification is an innovative strategy to realized functionalization, which may have a strong potential in clinical application.

Methacrylated hyaluronic acid/laponite photosensitive, sustained-release hydrogel loaded with bilobalide for enhancing random flap survival through mitigation of endoplasmic reticulum stress.

Random flaps are extensively utilized in plastic surgery due to their flexibility compared to traditional axial vascular system arrangements and their resemblance to injured skin in color, thickness, and texture. Despite these advantages, they are susceptible to ischemia-reperfusion injuries and subsequent necrosis post-transplantation. Bilobalide (BB), a sesquiterpene compound derived from Ginkgo biloba, exhibits notable antioxidant and anti-inflammatory properties and is commonly used to treat ischemiareperfusion injuries. However, its short half-life restricts its sustained efficacy in random flaps. In this study, we synthesized a multi-crosslinked, photosensitive methacryloyl hyaluronic acid(HAMA)/laponite(Lap)/bilobalide (BB) hydrogel. This dualcrosslinked hydrogel demonstrates superior mechanical properties and biocompatibility while providing a stable release of bilobalide. In vitro experiments showed that it significantly reduces edema, promotes angiogenesis, and enhances the survival of random flaps. Further network pharmacology analysis and recovery experiments suggested that the hydrogel's beneficial effects are mediated by the regulation of endoplasmic reticulum stress and specifically identified the regulation of the PERK/TXNIP/NLRP3 signaling pathway as crucial to its anti-inflammatory effects. Therefore, this HAMA/Lap/BB hydrogel promotes the survival of random flaps in rats by alleviating endoplasmic reticulum stress, providing a novel intervention strategy for the treatment of random flaps injuries.

Optimization of a gelatin/carboxymethylcellulose-based probiotic microcapsule and its application in preventing dextran sodium sulfate-induced colitis in mice.

Oral administration of probiotics has demonstrated substantial potential in alleviating colitis. However, most of the ingested microorganisms struggle to survive the harsh conditions of the gastrointestinal tract, leading to decreased efficacy. In the present study, using double emulsification (W1/O/W2) and complex coacervation methods, we developed a gelatin/carboxymethyl cellulose (CMC)-based probiotic microcapsule and analyzed the efficacy of encapsulated probiotics in preventing dextran sodium sulfate (DSS)-induced colitis in mice. Our results reveal that nearly 90% of the encapsulated probiotics remained viable after 30-day storage at 4°C and approximately 38.1% of viable bacteria (4.0 × 108 cfu/g) survived after 4-h simulated gastrointestinal digestion. In a DSS-induced colitis model, pretreatment with probiotics exerted significant protective effects, with the bacterial microcapsule-treated group having superior outcomes to those of the bacterial suspension plus empty carrier group. Probiotic treatments, especially those administered in the encapsulated form, significantly increased fecal short-chain fatty acid contents, and altered the intestinal microbial composition. The family Muribaculaceae, dominant bacteria in the mouse gut, may be the key microorganism involved in the BM regulation process. Our study presents an alternative approach to treating colitis using probiotics. PRACTICAL APPLICATION: The encapsuled probiotic showed remarkable storage stability at 4°C, maintained good vitality after simulated digestion, and gained superior outcomes in preventing colitis. Our results offer an alternative approach for the probiotic preparations aiming to prevent the intestinal inflammation.

Inhibitory effects of chlorhexidine-loaded calcium carbonate nanoparticles against dental implant infections.

This study aimed to design sustained released biodegradable calcium carbonate nanoparticles loaded with chlorhexidine (CHX-loaded NPs) and to investigate the early osteogenic differentiation and antimicrobial effects on the important bacteria involved in infections of dental implants. The microemulsion method was used to prepare the calcium carbonate nanoparticles loaded with chlorhexidine. The prepared nanoparticles were characterized using conventional methods. The release pattern determination and the biodegradation test were performed for the prepared nanoparticles. For the early osteogenic differentiation test of the prepared nanoparticles, alkaline phosphatase (ALP) activity was detected in human dental pulp stem cells (HDPSCs). The antimicrobial effects of the nanoparticles were evaluated against Escherichia coli, Streptococcus mutans, Enterococcus faecalis, Staphylococcus aureus, and Pseudomonas aeruginosa. The sizes of free calcium carbonate nanoparticles and CHX-loaded NPs were 105 ± 1.63 and 118 ± 1.47 nm and their zeta potentials were - 27 and - 36, respectively. A 50% degradation of nanoparticles was achieved after 100 days. These nanoparticles showed a two-stage sustained release pattern in vitro. Microscopic images revealed that the morphology of free calcium carbonate nanoparticles primarily took on a spherical calcite form, while CHX-loaded NPs predominantly exhibited a cauliflower-like vaterite polymorph. The nanoparticles increased the activity of ALP in cells in two weeks significantly (p < 0.05). Antimicrobial and antibiofilm results showed an efficient effect of the prepared nanoparticle against the studied bacteria. Calcium carbonate nanoparticles are an efficient multifunctional vector for chlorhexidine and can be used as a bioactive antibacterial agent against various oral microorganisms to prevent implant infections.

Thermosensitive multivesicular liposomal hydrogel: a potential platform for loco-regional drug delivery in the treatment of osteomyelitis caused by antibiotic-resistant biofilm-forming bacteria.

Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL)-loaded MVLs (VAN HL-MVLs), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to 3 weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 h, the hydrogel formulation extended this release to 504 h. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 h and methicillin-resistant S. aureus biofilms within 72 h. It also eradicated preformed biofilms of S. aureus and methicillin-resistant S. aureus in 96 and 120 h, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies.

Low-dose estrogen release from silastic capsule enhanced flap wound healing in an animal model.

BACKGROUND: Deep and extensive wounds usually cannot be closed directly by suturing or skin grafting. Flap transplantation is typically used to reconstruct large wounds clinically. The flap survival is based on a stable blood perfusion. It is established that estrogen promotes wound healing and angiogenesis, and regulates the inflammatory response, leading to enhanced flap survival after transplantation. However, estrogen concentrations administered in previous studies were significantly higher than physiological levels, potentially causing systemic side effects. Estrogen-sustained-release silastic capsules can maintain blood serum estrogen closer to physiological levels. This study aimed to investigate whether administering estrogen at a lower concentration, closer to physiological levels, could still enhance flap survival. MATERIALS AND METHODS: This study was performed in a random skin flap model in ovariectomized (OVX) mice. Sustained-release estrogen silastic capsules were implanted into OVX mice to determine the functional role of estrogen in wound healing after flap transplantation. Flap blood perfusion was analysed using a colour laser Doppler scanner. Immunohistochemical staining of CD31, hypoxia-inducible factor 1 alpha (HIF-1α), alpha-smooth muscle actin (α-SMA), cleaved caspase 3 and apoptotic terminal dUTP nick end-labelling stain was used to investigate flap angiogenesis, tissue hypoxia, wound healing and cell death in the flap tissue, respectively. RESULTS: We observed that administering estrogen at a lower concentration enhanced superficial blood perfusion while reducing the flap's ischemic area and tissue necrosis. HIF-1α expression was significantly decreased in the dermis layer but not in the fascia, whereas cleaved caspase 3 levels decreased in the fascia but remained unchanged in the dermis. Additionally, there was no significant difference in CD31and α-SMA expression between the groups. CONCLUSION: In summary, the study showed that an estrogen silastic capsule maintained physiological estrogen levels and improved superficial perfusion, thereby reducing dermal hypoxia, and cell death in a mouse random pattern skin flap model. Although no significant promotion of angiogenesis was observed, the study suggests that appropriate estrogen supplements could enhance flap wound recovery.

Electrospun chitosan//ethylcellulose-vitamin E//ethylcellulose-curcumin tri-chamber eccentric Janus nanofibers for a joint antibacterial and antioxidant performance.

Multifunctional materials with both antibacterial and antioxidant properties are highly desired in many scientific applications. The combination of polysaccharide and multi-chamber nanostructures offers a novel perspective for developing antibacterial and antioxidant nanomaterials. In this study, a new kind of tri-chamber eccentric Janus nanostructures (TEJNs) was fabricated through a single-step and straight forward tri-fluid side-by-side electrospinning. The all-in-one TEJNs contained an outer chitosan (CS) chamber, a middle and an inner ethylcellulose (EC)-based chamber loaded with curcumin (Cur) and vitamin E (VE), respectively. The side-by-side multiple-fluid electrospinning processes were implemented robustly and continuously based on a homemade spinneret. Transmission electron microscope and scanning electron microscope evaluations demonstrated the tri-chamber inner structures of TEJNs and the linear morphologies, respectively. The Fourier transform infrared and X-ray diffraction results verified that the components were compatible and coexisted in an amorphous state. In vitro dissolution tests indicated that the TEJNs could provide a sustained release of 90 % of the loaded Cur and VE for 34.30 h and 24.86 h, respectively. Antibacterial and antioxidant experiments demonstrated that the TEJNs were able to provide enhanced antibacterial and antioxidant effects compared to the traditional electrospun homogeneous nanofibers. In the future, the Janus nanofibers can be further developed for several human health applications, such as wound dressings, active food packaging membranes, dental implants and cosmetic films.

Development of Ampelopsis Radix Ethanolic Extract Loaded Phytosomes for Improved Efficacy in Colorectal Cancer: in vitro and in vivo Assessment Study.

The aim of present work was to develop and evaluate Ampelopsis Radix ethanolic extract loaded phytosomes for improved efficacy in colorectal cancer. Ampelopsis Radix ethanolic extract was prepared by Soxhlet extraction process followed by development of phytosomes using lipids and other excipients. The phytosomes were evaluated for surface morphology, particle size analysis, zeta potential, encapsulation efficiency, drug loading, in vitro drug release, Cytotoxicity assay, cellular uptake studies were performed on HCT-116 and SW480 cell lines. In vivo antitumor activity was performed. The phytosomes were found spherical shape with smooth surface characteristics. The drug loading was observed between 29.27 to 42.10 % while particle size of 85 to 130 nm was found. Phytosomes showed desired release pattern which is required for cancer treatment. Phytosomes showed maximum antiproliferative activity on cell lines over the period of 24 hours and showed highest internalization within both types of cell lines. The survival rate of animals in phytosomes treated group was found to be 100% proving the safety and efficacy. Phytosomes showed highest antitumor activity as compared to other formulations. Study confirms the potential use Ampelopsis Radix ethanolic extract loaded phytosomes for improved efficacy in colorectal cancer.

Novel long-acting treatment for schizophrenia based on paliperidone dissolving and implantable microarray patches.

Schizophrenia is a severe mental disorder that affects millions of people worldwide. Several atypical antipsychotic medications, including paliperidone (PPD), has been developed and proven effective in treating it. To date, four PPD extended-release products have been launched commercially, providing up to six months of therapeutic effect with a single administration. However, the need for hospital injections by professional healthcare workers not only lead to poor patients' adherence, but also put additional pressure on the healthcare system. Therefore, three PPD microarray patch (PPD MAP) systems based on dissolving microneedle technology and implantable microneedle technology were developed in this work. The two dissolving microarray patch systems contained either PPD crude drug (PPD DMAP-CD) or PPD nanocrystal (PPD DMAP-NC) and the implantable MAP contained PPD crude drug (PPD IMAP). All three types of PPD MAPs showed excellent mechanical and insertion properties as they achieved over 256 µm insertion depth in skin model. In vitro release study showed that PPD released from IMAP in a much more sustained manner (up to 14 days) than PPD did from DMAPs (7 days), with only 20 % initial burst release from IMAP compared with 43-71 % from DMAPs. The MAP dissolution study showed that both DMAPs can be immediately dissolved within less than 3 min once inserted into the skin, indicating a faster action potential compared with IMAP. Ex vivo delivery study showed that 1.68 ±â€¯0.23 mg, 1.39 ±â€¯0.07 mg, and 1.18 ±â€¯0.12 mg were delivered from DMAP-CD, DMAP-NC and IMAP, respectively, demonstrating that over 50 % and up to 70 % of PPD in the MAPs can be delivered into the skin. The IMAP offers most sustained release of PPD whereas DMAP-NC exhibits fastest PPD release (11.19 % vs 20.01 % into Franz cell receiver compartment over 24 h). This work presents a promising alternative for the sustained delivery of antipsychotic drugs, allowing for patient self-administration and extended release concurrently. Patients may potentially use both DMAP and IMAP to achieve a sustained release of PPD while also avoid having an initial therapeutic lag.

Nanomedicine in glaucoma treatment; Current challenges and future perspectives.

Glaucoma presents a significant global health concern and affects millions of individuals worldwide and predicted a high increase in prevalence of about 111 million by 2040. The current standard treatment involves hypotensive eye drops; however, challenges such as patient adherence and limited drug bioavailability hinder the treatment effectiveness. Nanopharmaceuticals or nanomedicines offer promising solutions to overcome these obstacles. In this manuscript, we summarized the current limitations of conventional antiglaucoma treatment, role of nanomedicine in glaucoma treatment, rational design, factors effecting the performance of nanomedicine and different types of nanocarriers in designing of nanomedicine along with their applications in glaucoma treatment from recent literature. Current clinical challenges that hinder real-time application of antiglaucoma nanomedicine are highlighted. Lastly, future directions are identified for improving the therapeutic potential and translation of antiglaucoma nanomedicine into clinic.

Reverse Gradient Distributions of Drug and Polymer Molecules within Electrospun Core-Shell Nanofibers for Sustained Release.

Core-shell nanostructures are powerful platforms for the development of novel nanoscale drug delivery systems with sustained drug release profiles. Coaxial electrospinning is facile and convenient for creating medicated core-shell nanostructures with elaborate designs with which the sustained-release behaviors of drug molecules can be intentionally adjusted. With resveratrol (RES) as a model for a poorly water-soluble drug and cellulose acetate (CA) and PVP as polymeric carriers, a brand-new electrospun core-shell nanostructure was fabricated in this study. The guest RES and the host CA molecules were designed to have a reverse gradient distribution within the core-shell nanostructures. Scanning electron microscope and transmission electron microscope evaluations verified that these nanofibers had linear morphologies, without beads or spindles, and an obvious core-shell double-chamber structure. The X-ray diffraction patterns and Fourier transform infrared spectroscopic results indicated that the involved components were highly compatible and presented in an amorphous molecular distribution state. In vitro dissolution tests verified that the new core-shell structures were able to prevent the initial burst release, extend the continuous-release time period, and reduce the negative tailing-off release effect, thus ensuring a better sustained-release profile than the traditional blended drug-loaded nanofibers. The mechanism underlying the influence of the new core-shell structure with an RES/CA reverse gradient distribution on the behaviors of RES release is proposed. Based on this proof-of-concept demonstration, a series of advanced functional nanomaterials can be similarly developed based on the gradient distributions of functional molecules within electrospun multi-chamber nanostructures.