Burst Release Research Articles

A photo-modulated nitric oxide delivering hydrogel for the accelerated healing of biofilm infected chronic wounds

Biofilm infection and impaired healing of chronic wounds are posing tremendous challenges in clinical practice. In this study, we presented a versatile antimicrobial hydrogel capable of delivering nitric oxide (NO) in a controllable manner to dissipate biofilms, eliminate microorganisms, and promote the healing of chronic wounds. This hydrogel was constructed by Schiff-base crosslinking of oxidized dextran and antimicrobial peptide ε-poly-lysine, further encapsulating photothermal nanoparticles bearing NO donor. This hydrogel could continuously and slowly release NO, effectively dissipating biofilms, and promoting the proliferation of mouse fibroblasts and the migration of endothelial cells. Upon exposure to NIR laser irradiation, the hydrogel generated hyperthermia and rapidly released NO, resulting in the efficient elimination of a broad spectrum of drug-resistant Gram-positive/negative bacterial and fungal biofilms through the synergistic effects of NO, photothermal therapy, and the antibacterial peptide. Notably, the hydrogel demonstrated exceptional in vivo therapeutic outcomes in accelerating the healing process of mice diabetic wounds infected with methicillin-resistant Staphylococcus aureus by successfully eliminating biofilm infection, regulating inflammation, and facilitating angiogenesis and collagen deposition. Overall, this proposed hydrogel shows great promise in accommodating the various demands of the complex repair process of chronic wounds infected with biofilms. Statement of significanceThe presence of biofilm infections and underlying dysfunctions in the healing process made chronic wound become stuck in the inflammation stage and difficult to heal. This work developed a NIR laser-modulated three-stage NO-releasing versatile antimicrobial hydrogel (DEPN) exhibiting good therapeutic efficacy for chronic wound. This DEPN hydrogel could inherently and slowly released NO to disperse biofilm. Upon NIR laser irradiation, the DEPN hydrogel generated hyperthermia and induced a rapid burst release of NO effectively eliminating a broad spectrum of drug-resistant bacterial and fungal biofilms. Subsequently, the DEPN hydrogel continually release NO slowly to promote the tissue remolding. This DEPN hydrogel displays great potential in treatment of chronic wounds infected with biofilm.

Synergistic Effects of Radical Distributions of Soluble and Insoluble Polymers within Electrospun Nanofibers for an Extending Release of Ferulic Acid.

Polymeric composites for manipulating the sustained release of an encapsulated active ingredient are highly sought after for many practical applications; particularly, water-insoluble polymers and core-shell structures are frequently explored to manipulate the release behaviors of drug molecules over an extended time period. In this study, electrospun core-shell nanostructures were utilized to develop a brand-new strategy to tailor the spatial distributions of both an insoluble polymer (ethylcellulose, EC) and soluble polymer (polyvinylpyrrolidone, PVP) within the nanofibers, thereby manipulating the extended-release behaviors of the loaded active ingredient, ferulic acid (FA). Scanning electron microscopy and transmission electron microscopy assessments revealed that all the prepared nanofibers had a linear morphology without beads or spindles, and those from the coaxial processes had an obvious core-shell structure. X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopic tests confirmed that FA had fine compatibility with EC and PVP, and presented in all the nanofibers in an amorphous state. In vitro dissolution tests indicated that the radical distributions of EC (decreasing from shell to core) and PVP (increasing from shell to core) were able to play their important role in manipulating the release behaviors of FA elaborately. On one hand, the core-shell nanofibers F3 had the advantages of homogeneous composite nanofibers F1 with a higher content of EC prepared from the shell solutions to inhibit the initial burst release and provide a longer time period of sustained release. On the other hand, F3 had the advantages of nanofibers F2 with a higher content of PVP prepared from the core solutions to inhibit the negative tailing-off release. The key element was the water permeation rates, controlled by the ratios of soluble and insoluble polymers. The new strategy based on core-shell structure paves a way for developing a wide variety of polymeric composites with heterogeneous distributions for realizing the desired functional performances.

Chitosan/Sodium Alginate Hydrogel for the Release of Berberine as an Algae Suppressant: RSM Optimization and Analysis of Sustained Release Characteristics.

In this study, we used chitosan/sodium alginate hydrogel as a carrier to prepare berberine sustained-release capsule materials that can inhibit algae for a long time and safely. The preparation conditions of the material were optimized by the response surface method, and the optimized capsule material was characterized and the sustained release characteristics were analyzed to study the change of the algae inhibition effect of the material within 30 days. The results showed that the optimum preparation parameters of the material were 0.54% chitosan content, 2.46% sodium alginate content and 1.09% anhydrous calcium chloride content by response surface optimization design, which was consistent with the parameters set by each factor at the central point. The algae inhibition rate of the material under this preparation condition was 93.75 ± 1.01%, which was similar to the predicted value. The release characteristics analysis showed that the material continuously released up to 90% of berberine within 24 days, and its release characteristics were sustained release after burst release, with good sustained release effect. The results of material characterization showed that chitosan/sodium alginate hydrogel could effectively load berberine and was beneficial to the loading and release of berberine. The results of algae inhibition experiments showed that low concentration materials could control the outbreak of cyanobacterial blooms in a short time, while under high concentration conditions, the materials could inhibit Microcystis aeruginosa efficiently and for a long time.

Fabrication of Famotidine Loaded Sepiolite/Pectin Bionanocomposite Hydrogels for Controlled Drug Delivery

AbstractDevelopment of drug delivery systems is an extensively researched area in the biomedical field. In recent years, there has been an increasing interest in fabrication of biocompatible nanofibrous drug delivery systems. The present study describes the fabrication of calcium chloride‐crosslinked bionanocomposite hydrogels based on pectin for the use of gastro‐retentive delivery system. Sepiolite/famotidine/pectin nanocomposite hydrogel was fabricated by using Ionotropic gelation process. The thermal, structural and morphological properties were evaluated via different experimental techniques such as TGA‐DSC, FTIR, and SEM. The prepared hydrogels showed a pH sensitive swelling profile with maximum water absorption at pH 1.2. Analysis of in‐vitro drug release data revealed that the sepiolite/famotidine/pectin nanocomposite hydrogels exhibited a slight initial burst release, followed by a sustained release over a 24 h period. This was observed both in simulated gastric fluid and in phosphate‐buffered saline, suggesting that these hydrogels are well‐suited for prolonged drug delivery. To investigate the drug release kinetics, various models were applied. The release of famotidine was predominantly governed by diffusion, as described by the Korsmeyer‐Peppas model.

Macrolide-loaded nanofibrous inserts with polycaprolactone and cellulose acetate base for sustained ocular delivery: Pharmacokinetic study in Rabbit’s eye

The present study aimed to prepare nanofibrous inserts for sustained ocular drug delivery of Azithromycin (AZM) toward conquering the obstacles of conventional topical drug delivery. Nanofibers were fabricated by electrospinning using polycaprolactone (PCL) and cellulose acetate (CA) which are biocompatible and biodegradable polymers. Prepared nanofibers were evaluated in terms of physicochemical, morphological properties, pharmacokinetic study and ocular irritation. SEM images revealed average diameters of about 160 nm and 190 nm for CA and PCL nanofibers, respectively. These ocular drug delivery systems were strong, flexible, and stable under humid and dry conditions. Quantification was performed using microbiological assay by M. luteus as a microorganism. While PCL-based nanofibrous inserts released AZM in a two-step manner initiated by a burst release via Peppas kinetical model, CA-based inserts showed a gradual release profile without any burst release which followed the first-order model. Results showed that these inserts were non-cytotoxic and non-irritating. The nanofibers showed antibacterial efficacy against Escherichia coli and Staphylococcus aureus. In addition, according to a pharmacokinetic study in Rabbit’s Eye, a higher Cmax and lower Tmax were achieved by PCL nanofibers compared to CA-based ones. The pharmacokinetic study of nanofibers in rabbit eyes showed that all formulations were able to maintain the effective concentration of AZM for about 6 days. In conclusion, the prepared nanofibers can be effectively utilized for prolonged ocular delivery of AZM in the treatment of conjunctival infections.

Formulation of Dual-Functional Nonionic Cetomacrogol Creams Incorporated with Bacteriophage and Human Platelet Lysate for Effective Targeting of MDR P. aeruginosa and Enhanced Wound Healing.

Successful development of phage-based therapeutics and their utility predominantly depend on the mode and route of phage administration. Topical and site-directed phage application evokes minimal immune clearance and allows more phage-host adsorption, thereby ensuring higher phage efficacy. However, a notable drawback of conventional topical phage applications is the absence of sustained release. Occlusive emollients guarantee the controlled release of active pharmaceutical ingredients (APIs), thereby facilitating administration, preventing moisture loss, and acting as a skin barrier. In this study, we developed phage and human platelet lysate (h-PL) incorporated cetomacrogol-based creams for combined phage therapy and wound healing. The base material for phage immobilization was formulated by emulsifying paraffin and sterile water with cetomacrogol (emulsifying agent). Specifically, we incorporated a Pseudomonas aeruginosa-infecting lytic phage vB_PaeM_M12PA in the formulation and characterized its genome in this study. Cetomacrogol, a nonionic PEG (polyethylene glycol) based ether, rendered phage stability and allowed initial burst release followed by continuous controlled release of phages from the embedding matrix in the initial 6-8 h. Rheological studies showed that the material has elastic properties with storage moduli (G') values ranging from 109.51 ± 2.10 to 126.02 ± 3.13 kPa, indicating frequency-independent deformation. Platelet lysates in the cream acted as wound healing agents, and in vitro evaluation of cell migration and wound healing capacity of h-PL showed a significant enhancement by the sixth hour compared to untreated groups. The phage-incorporated cream showed sustained phage release in solid media and a significant reduction in bacterial growth in liquid cultures. In vivo wound healing studies in 6-week-old Wistar rats with full-thickness excision wounds and subsequent histopathological studies showed that the formulation enhanced wound healing and tissue restoration efficiency. In conclusion, the study unveils a promising approach for integrated phage therapy and wound healing strategies.

Pullulan-DOX/PVA-PDMS Biopolymeric Core-Shell Nanofibers Potential for Drug Delivery Systems

In this research, a novel drug delivery system shell was created by loading doxorubicin hydrochloride (DOX) into Pullulan and integrating the core into a polyvinyl alcohol (PVA) and Polydimethoxysilane (PDMS) composite matrix. The incorporation of DOX into the pullulan solution was carried out to take advantage of Pullulan's biocompatibility, biodegradability and hydrophilic nature. The hydrophilic nature of PVA can result in rapid drug release, while the hydrophobic nature of PDMS allows for slower drug release. The use of PVA-PDMS polymers together in the shell offers an initial rapid release followed by a prolonged and controlled drug release. This combination is superior to PVA or PDMS in terms of safety, mechanical strength, flexibility, controlled drug release and structural stability. This innovative composite system was designed to optimise DOX's controlled release to increase its therapeutic efficacy and reduce systemic toxicity. The kinetics of the drug release was characterised by an initial burst release followed by a sustained release phase, allowing controlled and prolonged release of the chemotherapeutic agent. Our results indicate that the pullulan/PVA-PDMS composite is a promising candidate for practical drug delivery applications, especially in cancer therapy.

Green synthesis of chitosan nanoparticles using Cassia fistula leaf extract: evaluation of antimicrobial, antioxidant, antibiofilm, and cytotoxic activities.

The emerging field of green synthesis within nanobiotechnology presents significant environmental and economic advantages compared to conventional methodologies. This study investigates the synthesis and application of chitosan nanoparticles (ChNPs) using Cassia fistula (CF) leaf extract as a sustainable, and bio-based approach. Characterization of CF-ChNPs confirmed effective bioconversion and also demonstrated significant antimicrobial activity. Notably, CF-ChNPs demonstrated a remarkable antimicrobial effect against Pseudomonas aeruginosa, with a zone of inhibition of 17 ± 0.2mm surpassing the impact on other organisms tested. The CF-ChNPs exhibited an initial burst release of 28 ± 0.28% after 2h, gradually achieving a controlled release of 76.3 ± 0.43% within 24h. In addition, CF-ChNPs exhibited an antioxidant activity of 43.1 ± 0.48% and showed excellent antibiofilm activity against Staphylococcus aureus in comparison to other organisms. The cell viability assay results have confirmed that CF-ChNPs do not have any negative impact on the viability of L929 fibroblasts, further highlighting their potential as versatile nanomaterials for treating microbial infections and other therapeutic applications.

Preparation irinotecan hydrochloride loaded PEGylated liposomes using novel method supercritical fluid and condition optimized by Box–Behnken design

A semi-synthetic camptothecin derivative known as irinotecan hydrochloride is frequently used to treat colorectal cancer, including colorectal adenocarcinoma and lung cancers involving small cells. Irinotecan has a very short half-life; therefore, continuous infusions are required to keep the drug’s blood levels at therapeutic levels, which could produce cumulative toxicities. Effective delivery techniques, including liposomes, have been developed to address these shortcomings. In this study, a continuous supercritical fluid approach dubbed Expansion Supercritical Fluid into an aqueous solution, in which the pressure decreases rapidly but remains over the critical pressure, is proposed to manufacture polyethylene glycolylated (PEGylated) liposomes carrying irinotecan hydrochloride. To accomplish this, PEGylated liposomes were created using a Box–Behnken design, and the operating parameters (flow rate, temperature, and pressure drop) were optimized. Encapsulation efficiency, mean size, and prepared liposome count were 94.6%, 55 nm, and 758 under ideal circumstances. Additionally, the stability of the PEGylated liposome was investigated during 8 weeks, and also PEGylated liposome-loaded irinotecan release profile was compared to conventional liposomes and free irinotecan, and a constant drug release was seen after the first burst release from liposomes.

Novel pH-Responsive Structural Rearrangement of Myristic Acid-Conjugated Quetiapine Nanosuspension for Enhanced Long-Acting Delivery Performance.

Quetiapine myristate (QM), an ester-bonded lipophilic prodrug of quetiapine (QTP), is synthesized and converted into an amphiphilic structure in acidic pH to trigger a novel self-assembled QM nanosuspension (QMN). Following injection, this QMN rearranges within physiological pH to form nanoaggregates in structure, resulting in enhanced physicochemical properties and in vivo therapeutic performance without an initial burst release. The 200-nm-sized QMN exhibits less invasive injection, higher drug content, and better storage stability profile than conventional poly(lactide-co-glycolide) (PLGA) nanosuspensions containing QTP or QM. Following a single intramuscular injection to beagle dogs (35mg kg-1 QTP), QMN undergoes pH-responsive nanoaggregation to form the lipophilic prodrug, providing esterase-oriented sustained release for five weeks compared with the two-week period of PLGA nanosuspensions. Notably, QMN exhibits improved in vivo pharmacokinetic performance with long-acting delivery while minimizing issues associated with polymeric PLGA formulations, including the initial massive burst release, cellular toxicity, and adverse side effects. These results support the further development of QMN as a novel long-acting injectable to improve patient compliance and dosing frequency.

New Insights Into Application Relevant Properties of Cu2+-Doped Brushite Cements.

Doping of brushite cements with metal ions can entail many positive effects on biological and physicochemical properties. Cu2+ ions are known to exhibit antibacterial properties and can additionally have different positive effects on cells as trace elements, whereas high Cu2+ concentrations are cytotoxic. For therapeutical applications of bone cement, a combination of good biocompatibility and sufficient mechanical properties is required. Therefore, the aim of this study was to investigate different physicochemical and biological aspects, relevant for application, of a brushite cement with Cu2+-doped β-tricalcium phosphate, monocalcium phosphate monohydrate and phytic acid as setting retarder. Additionally, the ion release was compared with a cement with citric acid as setting retarder. The investigated cements showed good injectability coefficients, as well as compressive strength values sufficient for application. Furthermore, no antibacterial effects were detected irrespective of the Cu2+ concentration or the bacterial strain. The cell experiments with eluate samples showed that the viability of MC3T3-E1 cells tended to decrease with increasing Cu2+ concentration in the cement. It is suggested that these biological responses are caused by the difference in the Cu2+ release from the hardened cement depending on the solvent medium. Furthermore, the cements showed a steady release of Cu2+ ions to a lesser extent in comparison with a cement with citric acid as setting retarder, where a burst release of Cu2+ was observed. In conclusion, despite the anticipated antibacterial effect of Cu2+-doped cements was lacking and mammalian cell viability was slightly affected, Cu2+-concentrations maintained the physicochemical properties as well as the compressive strength of cements and the slow ion release from cements produced with phytic acid is considered advantageous compared to citric acid-based formulations.

Preparation of CS coated graded ordered porous ZrO2 implantable drug carrier

ZrO2 is bioceramic known for its excellent chemical stability and biocompatibility. Porous ZrO2, with its large surface area, has attracted considerable attention in the field of orthopedic implant drug delivery. However, the shortcomings of poor bioactivity and insufficient drug loading capacity in traditionally prepared porous ZrO2 limit its application. In this paper, graded ordered porous ZrO2 with interconnected open pores was prepared by colloid crystal templating, which exhibited large specific surface area and excellent slow-release properties. Then, it was surface-coated with chitosan (CS) possessing bioactivity and strong adsorption capacity. Factors affecting microscopic morphology, drug loading and slow-release properties of this composite were systematically investigated using ibuprofen (IBU) as a drug model. Results showed that graded ordered porous ZrO2 significantly enhanced drug loading capacity compared to normal ordered porous ZrO2, reaching 125.66 mg/g. Additionally, surface coating modification of the composite by CS significantly affected IBU loading capacity. By regulating process parameters such as CS concentration and coating time, high-efficiency loading of IBU was realized and drug loading capacity reached up to 194.17 mg/g. In vitro drug simulation experiments showed that CS coating effectively controlled the initial burst release of IBU and prolonged the effective release time; maximum cumulative release rate reached 93.7 %. This study provides a new idea for implantable drug sustained-release systems, which may better meet medical needs.

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 ± 0.23 mg, 1.39 ± 0.07 mg, and 1.18 ± 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.

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.

Preparation of alginate/vermiculite composite functionalized with silanol group for controlled drug delivery: Effect of CaCl2 concentration, release kinetics, cytotoxicity, and antimicrobial activities

In this study, alginate/vermiculite (Alg/VMT) hydrogel with 3-aminopropyl triethoxysilane (Alg/VSN) and tetraethoxysilane (Alg/VS) synthesized with various concentrations of CaCl2 (10 %–15 %–20 % M) to extend the release of 6-Aminopenicillanic acid (AP). Composites characterized by XRD, FTIR and BET. The result of Alg/VS composite shows an excellent loading of 243.90 mg/g through AP intercalated in the VMT layer. The equilibrium and Kinetic studies indicated that AP adsorption on Alg/VS and Alg/VSN was heterogeneous with chemical interaction. The in-vitro release Alg/VS showed a rapid burst release of 14 % in the first half an hour and only 75 % of the drug remained in the composite. Whereas, the in-vitro release Alg/VSN showed substantially less burst release with the cumulative release of 9 % (in the first 0.5 h). In-vitro release kinetics in the presence of CaCl2 concentrations showed that maximum 19 % of AP released within 12 h. The kinetic release was followed by a controlled release pattern (Korsmeyer-Peppas model) with Fick's law mechanism. The composites behaved as barriers against cell growth and had better biocompatibility against standard strains of Pseudomonas aeruginosa and Methicillin-Resistant Staphylococcus. MTT assay results from per cent cell viability composites modified by silanol groups were 96 % the means samples were nontoxic. The types of newly synthesized composites were able to finely decrease cell toxicity and improve AP release in vitro.

Empowering Natural Medicine: Nanocarrier-based Oral Delivery of Vigna Radiata Extract for Effective Diabetes Management

Background: Poor solubility and low oral bioavailability are major challenges associated with the oral delivery of the antidiabetic drug Vigna radiata (VR). Nanostructured lipid carriers (NLCs) have emerged as a promising strategy to overcome these limitations and improve the therapeutic efficacy of VR. This study investigated the potential of NLCs for VR delivery and explored the influence of formulation parameters on NLC properties and drug release behavior. Method: NLCs loaded with VR were prepared using the melt emulsion ultrafiltration technique. The effect of two key formulation variables – the ratio of liquid lipid to solid lipid and the concentration of the surfactant – were investigated in terms of particle size, zeta potential, and drug encapsulation efficiency. The in vitro release profiles of the VR-NLC formulations were evaluated, and the optimal formulation was subjected to further analysis to investigate its release kinetics. Result: The NLCs exhibited particle sizes ranging from 108.9 to 192.3 nm and all formulations possessed a negative zeta potential (-3.68 to -10.9 mV), indicating good stability and potential for resisting aggregation. Interestingly, the lowest solid lipid to liquid lipid ratio and the lowest surfactant concentration yielded the highest drug encapsulation efficiency, highlighting the complex interplay between these factors. All VR-NLC formulations exhibited a biphasic, time-dependent in vitro release pattern, suggesting an initial burst release followed by a sustained release phase. This biphasic profile is promising for achieving both rapid onset of action and long-lasting glycemic control, which are crucial aspects of effective diabetes management. The optimized NLC formulation showed an in vitro release pattern that adhered to the Higuchi diffusion model, suggesting a controlled release mechanism where the drug diffuses steadily out of the NLC matrix. This finding indicates potentially predictable and consistent drug delivery in vivo. Conclusion: This study demonstrates the potential of NLCs as a promising platform for the controlled oral delivery of VR. NLCs can overcome the inherent limitations of VR and provide a convenient and effective oral antidiabetic option for patients. Further research is needed to confirm the efficacy and safety of NLC-encapsulated VR in vivo using relevant animal models. This will pave the way for the development of a novel and potentially transformative treatment option for diabetes.

Injectable dual thermoreversible hydrogel for sustained intramuscular drug delivery

Herein, we reported novel docetaxel-decorated solid lipid nanoparticle (DCT-SLN)-loaded dual thermoreversible system (DCT-DRTS) for intramuscular administration with reduced burst effect, sustained release and improved antitumor efficacy. The optimized DCT-DRTs was subjected to in-vitro and in-vivo analyses. Antitumor evaluation of the DCT-DRTS was executed and compared with DCT-hydrogel, and DCT-suspension trailed by the histopathological and immune-histochemical analyses. The DCT-SLN gave a mean particle size of 157 nm and entrapment efficiency of 93 %. It was a solid at room temperature, and changed to liquid at physiological temperature due to its melting point of about 32 °C. Unlikely, poloxamer mixture remained liquefied at 25-27 °C, however converted to gel at physiological temperature. This behavior demonstrated opposed reversible property of the DCT-SLN and poloxamer hydrogel in DCT-DRTS system, making it ideal for intramuscular administration and quick gelation inside the body. The DCT-DRTS sustained the drugs release and unlike DCT-hydrogel, the preliminary plasma concentration of DCT-DRTS was significantly reduced, overcoming the burst release. A meaningfully enhanced antitumor efficacy and improved survival rate was observed from DCT-DRTS in tumor cell xenograft athymic nude mice. Additionally, increased apoptotic and reduced proliferation markers were observed in DCT-DRTS treated tumor masses. It was concluded that DCT-DRTS may be a suitable choice for intramuscular administration of DCT with sustained release, improved bioavailability, reduced toxicity and enhanced antitumor effects.

Exploring nalbuphine loaded chitosan nanoparticles for effective pain management through intranasal administration: a comparative study

Background Intranasal drug delivery shows potential for brain access via olfactory and trigeminal routes. Purpose This work aimed to ensure brain availability of nalbuphine via the nasal route. Method Chitosan based nanoparticles loaded with nalbuphine were successfully prepared using ionic gelation method and characterised. Result SEM results revealed that the nanoparticles were spherical in shape, with an average size of 192.4 ± 11.6 nm. Zeta potential and entrapment efficiency was found 32.8 mV and 88.43 ± 7.75%, respectively. The X-ray diffractometry and DSC results unravel a profound understanding on the physical and thermal characteristics. The in-vitro release of nalbuphine from the nanoparticles was biphasic, with an initial burst release followed by a slow-release profile. In-vitro cell study on HEK-293 cells and microscopic images of brain tissue confirmed the safety profile of formulation. In-vivo efficacy studies on animal confirmed the effectiveness of developed intranasal formulation as compared to the standard therapy. The in-vivo pharmacokinetic studies showed that the prepared nanoparticles were able to efficiently deliver nalbuphine to the brain in comparison to the other body organs. Gamma scintigraphy images showed retention of the drug in the brain. Furthermore, the efficacy studies confirmed that the nanoparticles were found significantly more effective than the marketed formulation in pain management.

Ultra-Long-Term Delivery of Hydrophilic Drugs Using Injectable In Situ Cross-Linked Depots.

Achieving ultra-long-term release of hydrophilic drugs over several months remains a significant challenge for existing long-acting injectables (LAIs). Existing platforms, such as in situ forming implants (ISFI), exhibit high burst release due to solvent efflux and microsphere-based approaches lead to rapid drug diffusion due to significant water exchange and large pores. Addressing these challenges, we have developed an injectable platform that, for the first time, achieves ultra-long-term release of hydrophilic drugs for over six months. This system employs a methacrylated ultra-low molecular weight pre-polymer (polycaprolactone) to create in situ cross-linked depots (ISCD). The ISCD's solvent-free design and dense mesh network, both attributed to the ultra-low molecular weight of the pre-polymer, effectively minimizes burst release and water influx/efflux. In vivo studies in rats demonstrate that ISCD outperforms ISFI by achieving lower burst release and prolonged drug release. We demonstrated the versatility of ISCD by showcasing ultra-long-term delivery of several hydrophilic drugs, including antiretrovirals (tenofovir alafenamide, emtricitabine, abacavir, and lamivudine), antibiotics (vancomycin and amoxicillin) and an opioid antagonist naltrexone. Additionally, ISCD achieved ultra-long-term release of the hydrophobic drug tacrolimus and enabled co-delivery of hydrophilic drug combinations encapsulated in a single depot. We also identified design parameters to tailor the polymer network, tuning drug release kinetics and ISCD degradation. Pharmacokinetic modeling predicted over six months of drug release in humans, significantly surpassing the one-month standard achievable for hydrophilic drugs with existing LAIs. The platform's biodegradability, retrievability, and biocompatibility further underscore its potential for improving treatment adherence in chronic conditions.

Sustained Antibiotic Release from Biodegradable Gelatin–Silica Hybrid for Orthopedic Infections

AbstractAntibiotic‐loaded polymethylmethacrylate (PMMA) beads are commonly employed to treat prosthetic joint infections (PJI) and chronic osteomyelitis due to their excellent mechanical strength. However, PMMA's non‐degradability results in a burst release of antibiotics and potential renal toxicity, necessitating additional surgeries for bead removal. There is a critical need for infection control materials that can deliver antibiotics effectively, maintain adequate mechanical strength, and degrade uniformly. This study introduces a gelatin–silica hybrid antibiotic carrier, characterized by covalent bonds between the gelatin and silica networks. The incorporation of the silica network enhances the compressive strength to 32.53 ± 2.4 MPa and ensures uniform degradation over 6 months, aligning with clinical timelines. Furthermore, the gelatin–silica hybrid can support up to 10 wt% antibiotic loading without compromising its properties, making it a promising candidate for next‐generation infection control materials.