Drug Delivery Research Articles

Niosome-encapsulated auraptene reduced the mRNA expression of VEGF-A and PDGFs genes in human retina-derived RPE cell line

AIM: To evaluate the effect of auraptene (AUR) treatment in forms of free and encapsulated in niosome nanoparticles by investigating the mRNA expression level of vascular endothelium growth factor (VEGF)-A and platelet-derived growth factors (PDGFs) in human retinal pigment epithelium (RPE) cell line. METHODS: Niosome nanocarriers were produced using two surfactants Span 60 and Tween 80. RPE cell line was treated with both free AUR and niosome-encapsulated. Optimum dosage of treatments was calculated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Expression of VEGF-A and PDGF-A, PDGF-B, PDGF-C, PDGF-D genes was measured after total RNA extraction and cDNA synthesis, using real-time polymerase chain reaction (RT-PCR). RESULTS: The highest entrapment efficiency (EE) was achieved by Span 60:cholesterol (1:1) with 64.3%. The half maximal inhibitory concentration (IC50) of free and niosome-encapsulated AUR were 38.5 and 27.78 µg/mL, respectively. Release study revealed that niosomal AUR had more gradual delivery to the cells. RT-PCR results showed reduced expression levels of VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D after treatment with both free and niosomal AUR. CONCLUSION: Niosomal formulation of Span 60: cholesterol (1:1) is an effective drug delivery approach to transfer AUR to RPE cells. VEGF-A, PDGF-A, PDGF-B, PDGF-C, and PDGF-D are four angiogenic factors, inhibiting which by niosomal AUR may be effective in age-related macular degeneration.

Evaluation of Doxorubicin-loaded Echogenic Macroemulsion for Targeted Drug Delivery.

The latest technology trend in targeted drug delivery highlights stimuliresponsive particles that can release an anticancer drug in a solid tumor by responding to external stimuli. This study aims to design, fabricate, and evaluate an ultrasound-responsive drug delivery vehicle for an ultrasound-mediated drug delivery system. The drug-containing echogenic macroemulsion (eME) was fabricated by an emulsification method using the three phases (aqueous lipid solution as a shell, doxorubicin (DOX) contained oil, and perfluorohexane (PFH) as an ultrasound-responsive agent). The morphological structure of eMEs was investigated using fluorescence microscopy, and the size distribution was analyzed by using DLS. The echogenicity of eME was measured using a contrast-enhanced ultrasound device. The cytotoxicity was evaluated using a breast cancer cell (MDA-MB-231) via an in vitro cell experiment. The obtained eME showed an ideal morphological structure that contained both DOX and PFH in a single particle and indicated a suitable size for enhancing ultrasound response and avoiding complications in the blood vessel. The echogenicity of eME was demonstrated via an in vitro experiment, with results showcasing the potential for targeted drug delivery. Compared to free DOX, enhanced cytotoxicity and improved drug delivery efficiency in a cancer cell were proven by using DOX-loaded eMEs and ultrasound. This study established a platform technology to fabricate the ultrasound-responsive vehicle. The designed drug-loaded eME could be a promising platform with ultrasound technology for targeted drug delivery.

Nanobots: Revolutionising the Next Generation of Biomedical Technology and Drug Therapy

Abstract: Nanoscale machines called “nanorobots” that were hitherto only futuristic ideas are set to storm healthcare and pharmaceuticals with newer technologies for minimally invasive diagnosis, quick and precise surgeries, and targeted drug delivery, which is challenging to achieve by conventional drug delivery systems. Nanobots can be defined as controllable nano-sized mechanical or electromechanical devices which are easily incorporated into cells and used for a variety of cellular functions like combating bacteria and viruses, disposing away dead cells/tissue at the place of a wound, cell/tissue repair and destruction of cancer cells, and also for transporting drugs to cells. Nanorobots can help avoid the untoward effects of traditional drug delivery systems and ameliorate the efficiency of drug delivery by quickly entering the desired cells without affecting other organs. With the advent of mobile communication, artificial neural networks, and Information Technology, futuristic and more advanced nanobots with artificial intelligence are in the offing. However, the challenges to this revolutionary technology are umpteen, the major concern being their interaction inside the human body. This review explicitly expounds on nanobots and their applications to medicine, biomedical research, and drug delivery.

Lipid-based Nanocarrier Drug Delivery Approach for Biomedical Application

Abstract: The development of nanosized drug-carrier systems has been investigated over the past few decades using various techniques. The two main categories of these systems are polymeric nanoparticles and lipid nanoparticles (LNPs). The toxicological risk associated with lipid nanoparticles is significantly lower than the danger associated with polymeric nanoparticles due to the materials' natural and biological origins. Lipid-based drug delivery systems like Nanostructured lipid carriers (NLCs) and Solid Lipid Nanoparticles (SLNs) are well-established nanotechnology systems for preparing all major pharmaceuticals. These delivery systems can be scaled up with easy manufacturing procedures and are biocompatible. NLCs are the second generation of lipid-based nanocarriers (SLNs), formed by combining solid and liquid biocompatible lipids to form an unstructured matrix that provides high entrapment efficiency of active constituents. LNPs can promote the distribution of active pharmaceutical ingredients to the target site. Increasing the active drug concentration to target organ LNPs enhances the therapeutic effectiveness and reduces the side effects. This paper reviews the structure of SLNs and different NLCs, various steps involved in manufacturing lipid nanoparticles, excipients used in the formulation, and applications for targeted drug delivery.

Trojan Microparticles : A Composite Nanoparticle Delivery System

Abstract: In recent years, microparticulate systems have drawn growing attention as a viable strategy for delivering cells, proteins, and medications to target areas. The Nanoparticles-in-Microparticles System (NiMS) is a drug delivery method that combines nano- and microparticles to deliver medications or genes to particular bodily regions with precision. A promising method for achieving dual or multiple functions inside a formulation is the development of nanoparticle-in-microparticle systems (NiMS). NiMS comprises a microparticle (M.P.) matrix and one or more nanoparticles (N.P.s). The N.P.s can be designed to provide specific functionality, such as targeted drug delivery or imaging, while the M.P. matrix can be tailored to provide sustained release or protect the N.P.s from degradation. NiMS offer several advantages over traditional formulations, including the ability to control release profiles and achieve site-specific delivery. By combining different types of N.P.s and M.P.s, it is possible to create formulations that release drugs at different rates or with different kinetics, allowing for tailored treatment regimens. Additionally, by lowering off-target effects and boosting efficacy, the site-specific targeting offered by NiMS can enhance the therapeutic index of medications. Microparticles are small, micron-sized particles that can be loaded with therapeutic agents and designed to deliver them to specific tissues in the body. The pharmaceutical sector is developing microparticulate delivery systems for oral, pulmonary, and cutaneous administration. For instance, a promising strategy for treating respiratory conditions, including asthma and chronic obstructive pulmonary disease, is the development of inhalable microparticles (COPD). Moreover, the use of microparticles for topical drug delivery is being studied, where they can be formulated into creams, gels, or patches for treating skin disorders. The composition of microparticles is crucial for successful tissue regeneration because the particles must be biocompatible and able to interact with the cells in the targeted tissue. In addition, the size and shape of the particles can affect their behavior and how they interact with cells. Chemical and biological sensors and devices, optical detectors, electronic components, and nanoscale production depend on nanostructures because they offer unique properties, such as increased surface area and enhanced reactivity, which can be exploited to create more efficient and effective devices.

Applications of nanotechnology-mediated herbal nanosystems for ophthalmic drug.

In recent years, herbal nanomedicines have gained tremendous popularity for novel drug discovery. Nanotechnology has provided several advances in the healthcare sector, emerging several novel nanocarriers that potentiate the bioavailability and therapeutic efficacy of the herbal drug. The recent advances in nanotechnology with accelerated strategies of ophthalmic nanosystems have paved a new path for overcoming the limitations associated with ocular drug delivery systems, such as low bioavailability, poor absorption, stability, and precorneal drug loss. Ophthalmic drug delivery is challenging due to anatomical and physiological barriers. Due to the presence of these barriers, the herbal drug entry into the eyes can be affected when administered by following multiple routes, i.e., topical, injectables, or systemic. However, the advancement of nanotechnology with intelligent systems enables the herbal active constituent to successfully entrap within the system, which is usually difficult to reach employing conventional herbal formulations. Herbal-loaded nanocarrier drug delivery systems demonstrated enhanced herbal drug permeation and prolonged herbal drug delivery. In this current manuscript, an extensive search is conducted for original research papers using databases Viz., PubMed, Google Scholar, Science Direct, Web of Science, etc. Further painstaking efforts are made to compile and update the novel herbal nanocarriers such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanostructure lipid carriers, micelles, niosomes, nanoemulsions, dendrimers, etc., which are mostly used for ophthalmic drug delivery system. This article presents a comprehensive survey of diverse applications used for the preventative measures and treatment therapy of varied eye disorders. Further, this article highlights the recent findings that the innovators are exclusively working on ophthalmic nanosystems for herbal drug delivery systems. The nanocarriers are promising drug delivery systems that enable an effective and supreme therapeutic potential circumventing the limitations associated with conventional ocular drug delivery systems. The nanotechnology-based approach is useful to encapsulate the herbal bioactive and prevent them from degradation and therefore providing them for controlled and sustained release with enhanced herbal drug permeation. Extensive research is still being carried out in the field of herbal nanotechnology to design an ophthalmic nanosystem with improved.

Application of Cell Penetrating Peptides for Intracellular Delivery of Endostatin: A Computational Approach.

Endostatin is an antiangiogenic compound with anticancer activity. The poor stability and low half-life of endostatin are the main barriers to the clinical use of this protein. Cell-penetrating peptides (CPPs) are extensively applied as carrier in the delivery of drugs and different therapeutic agents. Therefore, they can be proper candidates to improve endostatin delivery to the target cells. In this study, we aim to computationally predict appropriate CPPs for the delivery of endostatin. Potential appropriate CPPs for protein delivery were selected based on the literature. The main parameters for detection of best CPP-endostatin fusions, including stability, hydrophobicity, antigenicity, and subcellular localization, were predicted using ProtParam, VaxiJen, and DeepLoc-1.0 servers, respectively. The 3D structures of the best CPP-Endostatin fusions were modeled by the I-TASSER server. The predicted models were validated using PROCHECK, ERRAT, Verify3D and ProSA-Web servers. The best models were visualized by the PyMol molecular graphics system. Considering the principal parameters in the selection of best CPPs for endostatin delivery, endostatin fusions with four CPPs, including Cyt c-ss-MAP, TP-biot1, MPGα, and DPV1047, high stability and hydrophobicity, no antigenicity and extracellular localization were predicted as the best potential fusions for endostatin delivery. Four CPPs, including Cyt c-ss-MAP, TP-biot1, MPGα, and DPV1047, were predicted as the best potential candidates to improve endostatin delivery. Application of these CPPs may overcome the limitation of endostatin therapeutic applications, including poor stability and low half-life. Subsequent experimental studies will contribute to verifying these computational results.

Synthesis, characterization, and evaluation of the anticancer properties of pH-responsive carvacrol-zinc oxide quantum dots on breast cancer cell line (MDA-MB-231).

Since most solid tumors have a low pH value, a pH-responsive drug delivery system may offer a broad method for tumor-targeting treatment. The present study is used to analyze the anticancer activity of carvacrol-zinc oxide quantum dots (CVC-ZnO QDs) against breast cancer cells (MDA-MB-231). CVC-ZnO QDs demonstrate pH responsive and are specifically released within the acidic pH tumor microenvironment. This property enables targeted drug delivery exclusively to cancer cells while minimizing the impact on normal cells. To the synthesized ZnO QDs, the CVC was loaded and then examined by X-ray diffraction, ultraviolet-visible, Fourier transform infrared spectrophotometer, scanning electron microscopy-energy dispersive X-ray, and transmission electron microscopy. For up to 20 h, CVC release was examined in different pH-buffered solutions. The results showed that carvacrol release was stable in an acidic pH solution. Further, cytotoxicity assay, antioxidant, and lipid peroxidation activity, reactive oxygen species, mitochondrial membrane potential, nuclear damage, and the ability of CVC-ZnO QDs to cause apoptosis were all examined. Apoptosis markers such as Bcl2, Bax, caspase-3, and caspase-9, were also studied. In conclusion, the CVC-ZnO QDs destabilized the MDA-MB-231cells under its acidic tumor microenvironment and regulated apoptosis.

Nanotechnology-Based Drug Delivery of Topical Antifungal Agents.

Among the various prominent fungal infections, superficial ones are widespread. A large number of antifungal agents and their formulations for topical use are commercially available. They have some pharmacokinetic limitations which cannot be retracted by conventional delivery systems. While nanoformulations composed of lipidic and polymeric nanoparticles have the potential to overcome the limitations of conventional systems. The broad spectrum category of antifungals i.e. azoles (ketoconazole, voriconazole, econazole, miconazole, etc.) nanoparticles have been designed, prepared and their pharmacokinetic and pharmacodynamic profile was established. This review briefly elaborates on the types of nano-based topical drug delivery systems and portrays their advantages for researchers in the related field to benefit the available antifungal therapeutics.

The viscoelasticity of high concentration monoclonal antibodies using particle tracking microrheology.

The viscoelasticity of monoclonal antibodies (mAbs) is important during their production, formulation, and drug delivery. High concentration mAbs can provide higher efficacy therapeutics (e.g., during immunotherapy) and improved efficiency during their production (economy of scale during processing). Two humanized mAbs were studied (mAb-1 and mAb-2) with differing isoelectric points. Using high speed particle tracking microrheology, we demonstrated that the mAb solutions have significant viscoelasticities above concentrations of 40 mg/ml. Power law viscoelasticity was observed over the range of time scales (-1 s) probed for the high concentration mAb suspensions. The terminal viscosity demonstrated an exponential dependence on mAb concentration (a modified Mooney relationship) as expected for charged stabilized Brownian colloids. Gelation of the mAbs was explored by lowering the pH of the buffer and a power law scaling of the gelation transition was observed, i.e., the exponent of the anomalous diffusion of the probe particles scaled inversely with the gelation time.

Research Progress of Chitosan-based Multifunctional Nanoparticles in Cancer Targeted Therapy.

Conventional tumor therapeutic modalities, such as radiotherapy, chemotherapy, and surgery, involve low tumor inhibition efficiency, non-targeted drug delivery, and side effects. The development of novel and practical nano-drug delivery systems (DDSs) for targeted tumor therapy has become particularly important. Among various bioactive nanoparticles, chitosan is considered a suitable candidate for drug delivery due to its non-toxicity, good biocompatibility, and biodegradability. The amino and hydroxyl groups of chitosan endow it with the diverse function of chemical modification, thereby improving its physical and biological properties to meet the requirements of advanced biomedical applications. Therefore, it is necessary to review the property and applications of chitosan-based materials in biomedicine. In this review, the characteristics of chitosan related to its applications are first introduced, and then the preparation and modification of chitosan-based nanoparticles, including the function tailoring of chitosan-modified nanoparticles, are demonstrated and discussed. Finally, the opportunities and challenges of chitosan-based nanomaterials in this emerging field are proposed from the perspective of the rational and systematic design for the biomedicine field.

Overview of the Current Advancements and Trends in the Transungual Drug Delivery System

Background: Drug delivery across human nails is termed a transungual drug delivery system. It is recommended for the amelioration of nail disorders and infectious nail diseases like onychomycosis. Thereby, vivid anti-fungal regimens have been prescribed in the form of different types of formulations, including nail lacquers, nail film, nail paint, and other types for treating onychomycosis. Method: All the formulations currently marketed or being marketed for the transungal drug delivery system were thoroughly studied, compared, and evaluated for their advantages and disadvantages so that a new vision can be sustained along the path of creating newer anti-fungal transunguals, keeping in mind the anatomy of the nail and various parameters that govern bioavailability of active pharmaceutical ingredients across the nail bed. Accordingly, different techniques are devised to enhance permeation across the nail. The various parameters used to evaluate these formulations depend upon their physical, chemical, and mechanical properties. Conclusion: The recent approaches in transungual novel drug delivery systems have been reported while exemplifying a few patented and marketed formulations, along with the clinical trial status of these formulations. There is a need for the development of new techniques to overcome all the loopholes present in the ongoing treatment techniques and the formulations used nowadays for the treatments of diseases that occur in nails. After thoroughly detailing transungal novel drug delivery systems, we envisage great opportunities for the researchers to carry out novel work in chemotherapy through nails.

Emerging Aspects of Triazole in Organic Synthesis: Exploring its Potential as a Gelator.

Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) - commonly known as the "click reaction" - serves as the most effective and highly reliable tool for facile construction of simple to complex designs at the molecular level. It relates to the formation of carbon heteroatomic systems by joining or clicking small molecular pieces together with the help of various organic reactions such as cycloaddition, conjugate addition, ring-opening, etc. Such dynamic strategy results in the generation of triazole and its derivatives from azides and alkynes with three nitrogen atoms in the five-membered aromatic azole ring that often forms gel-assembled structures having gelating properties. These scaffolds have led to prominent applications in designing advanced soft materials, 3D printing, ion sensing, drug delivery, photonics, separation, and purification. In this review, we mainly emphasize the different mechanistic aspects of triazole formation, which includes the synthesis of sugar-based and non-sugar-based triazoles, and their gel applications reported in the literature for the past ten years, as well as the upcoming scope in different branches of applied sciences.

A Short Appraisal of Magnetic Nanoparticles for Breast Cancer: In vitro and In vivo Research.

The increasing incidence of breast cancer and the associated morbidity due to higher metastasis created the urge to develop a nanocarrier that can be used as a potent therapeutic carrier with targeting efficacy. The use of superparamagnetic nanoparticles in breast cancer research and treatment has gained considerable attention in recent years. Magnetic nanoparticles (MNPs) can be used to construct nanocarriers since they possess superior properties such as superparamagnetism, easy surface functionalization to attach ligands, and non-immunogenic. MNPs are superior carriers that are used to target cancer cells without harming the normal cells in the body, which leads to therapeutic efficacy in the body. Along with their established anticancer potential and enhanced drug concentration at endosomal pH, the superparamagnetic property of MNPs was further exploited for their applications in reticuloendothelial uptake, drug delivery, medical imaging, and theranostics applications in breast cancer. Moreover, the clinical translational of MNPs, along with future prospects and key challenges in vivo, have been duly presented in the final review. The scientists preferred the ongoing research in MNPs due to their high biocompatibility and ease of targeting at molecular and cellular levels. The review highlighted the in vitro and in vivo research and patent supported data for potential use of MNPs for the treatment of breast cancer.

DFT Study of Nanotubes as the Drug Delivery Vehicles for an Anticancer Drug

Abstract: Chemicals and poisons in the body interfere with the cell cycle and inhibit the growth of cancer cells. In this way, the function of chemicals in the body is controlled by taking anti-cancer drugs. Due to the degradability and compatibility of carbon nanotubes and boron nitride with the environment, they can act as suitable drug carriers for the transfer of anticancer drugs and deliver the drugs to the target cells. In the current work, the encapsulation of Formestane (FMS) anticancer drug into the carbon (CNT) and boron nitride (BNNT) (8,8) nanotubes was investigated for the first time using the density functional theory: B3LYP/3-21G* and the natural bond orbital analysis in the gas phase. Using natural bond orbital analysis, the charge transfer between FMS drug and CNT and BNNT nanotubes (8,8)/ FMS (BNNT/FMS) complexes were explored. Based on the results obtained from the calculation of encapsulation energy, it was found that the adsorption process was favorable. The interaction effects of FMS drug and CNT and BNNT (8,8) nanotubes on the natural bond orbital charge, the chemical shift parameters, and electronic properties were also evaluated. This study revealed that CNT and BNNT (8,8) nanotubes can be a suitable carrier for FMS drug delivery. The ultraviolet-visible spectra of the FMS drug, the CNT and BNNT (8,8), and the BNNT/FMS complexes were computed using time-dependent density functional theory (DFT: B3LYP) calculations.

Biomimetic “nano-spears” for CAFs-targeting: splintered three “shields” with enhanced cisplatin anti-TNBC efficiency

The treatment dilemma of triple-negative breast cancer (TNBC) revolves around drug resistance and metastasis. Cancer-associated fibroblasts (CAFs) contribute to cisplatin (Cis) resistance and further metastasis in TNBC, making TNBC a difficult-to-treat disease. The dense stromal barrier which restricts drug delivery, invasive phenotype of tumor cells, and immunosuppressive tumor microenvironment (TME) induced by CAFs serve as three “shields” for TNBC against Cis therapy. Here, we designed a silybin-loaded biomimetic nanoparticle coated with anisamide-modified red blood cell membrane (ARm@SNP) as a “nanospear” for CAFs-targeting, which could shatter the “shields” and significantly exhibit inhibitory effect on 4T1 cells in combination with Cis both in vitro and in vivo. The ARm@SNP/Cis elicited 4T1 tumor growth arrest and destroyed three “shields” as follows: disintegrating the stromal barrier by inhibiting blood vessels growth and the expression of fibronectin; decreasing 4T1 cell invasion and metastasis by affecting the TGF-β/Twist/EMT pathway which impeded EMT activation; reversing the immunosuppressive microenvironment by increasing the activity and infiltration of immunocompetent cells. Based on CAFs-targeting, ARm@SNP reversed the resistance of Cis, remodeled the TME and inhibited invasion and metastasis while significantly improving the therapeutic effect of Cis on 4T1 tumor-bearing mice, providing a promising approach for treating intractable TNBC.

Formulation and Characterisation of Fluconazole Loaded MCM-41 Powder for Topical Drug Delivery

Purpose: The use of common carriers like talc for topical drug delivery leads to diminished efficacy as a result of poor aqueous solubility and low dissolution rate. The objective of this study was to improve the efficiency of fluconazole topical dosage form using MCM-41 as a carrier material. The aim was to load fluconazole in carriers like MCM-41 as well as ß-Cyclodextrin and to compare the prepared powder formulation with the marketed formulations. Methods: Fluconazole complex was formulated with the use of MCM-41 and ß-CD as carriers in different proportions by melt, solvent evaporation and kneading method. The complex was developed into a powder formulation. These formulations were subjected to in vitro anti-fungal activity tests on candida albicans. Results: The inclusion compound was characterised by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and FTIR. The optimised method of preparation determined by in vitro dissolution was the melt method. The optimised formulation was then subjected to anti-fungal activity test. Formulation B containing MCM-41 as the bulk excipient had better performance than the marketed formulation; it showed 92.95 ± 0.33% CDR compared to 74.96 ± 0.47% CDR at the end of 1 hour and increased moisture adsorption. Conclusion: Thus, a fluconazole topical formulation with improved drug dissolution and moisture adsorption was designed. From in vitro tests, it was seen that the prepared formulation had better performance compared to the commercial formulation against skin mycotic infections and could be used for its treatment.

Decoding the mechanism governing the structural stability of wheat germ agglutinin and its isolated domains: A combined calorimetric, NMR, and MD simulation study.

Wheat germ agglutinin (WGA) demonstrates potential as an oral delivery agent owing to its selective binding to carbohydrates and its capacity to traverse biological membranes. In this study, we employed differential scanning calorimetry and molecular dynamics simulations to comprehensively characterize the thermal unfolding process of both the complete lectin and its four isolated domains. Furthermore, we present the nuclear magnetic resonance structures of three domains that were previously lacking experimental structures in their isolated forms. Our results provide a collective understanding of the energetic and structural factors governing the intricate unfolding mechanism of the complete agglutinin, shedding light on the specific role played by each domain in this process. The analysis revealed negligible interdomain cooperativity, highlighting instead significant coupling between dimer dissociation and the unfolding of the more labile domains. By comparing the dominant interactions, we rationalized the stability differences among the domains. Understanding the structural stability of WGA opens avenues for enhanced drug delivery strategies, underscoring its potential as a promising carrier throughout the gastrointestinal environment.

Fabrication of silastic testosterone enanthate implants to achieve virilizing levels of serum testosterone in swine

The aim of this study was to create a continuous drug delivery system that would yield serum testosterone levels in sexually mature, female pigs consistent with serum testosterone levels of human transgender men. Testosterone enanthate was mixed with medical grade silicone at a ratio of 20 % by weight, placed in silastic tubing to cure at room temperature for 24 hours, then removed from the tubing mold and stored at 4 ° C until surgical implantation. Testosterone enanthate oxidizes at high temperatures which is why the implants had to be stored cold. Each implant was 9 cm long and contained 0.56 g of testosterone enanthate. A minimum of one implant (0.56 g testosterone enanthate) and a maximum of four implants (2.24 g testosterone enanthate) were placed in the cervical subcutaneous fat of each pig. After implantation, serum testosterone was assessed over 40 days. Silastic testosterone enanthate implants increase serum testosterone and maintain it in a relatively constant state in a dose-dependent manner for ∼ 21 - 25 days post-implantation.Effective method for subcutaneous delivery of large quantities of testosterone or testosterone metabolites in compact implants to large animal biomedical model species.Maintains increased circulating testosterone levels for up to 3-4 weeks post-implantation in pigs.

Two-dimensional MXene-based nano-prodrug for synergistic chemo-photothermal therapy on cancer treatment

In cancer treatment, although prodrugs have been developed to overcome obstacles such as undesirable pharmacokinetic performance and serious off-target toxicity of most chemotherapeutics, the combination of prodrugs with nanotechnology could be used to overcome the shortcomings of conventional prodrug strategies and facilitate more efficient drug delivery and accumulation of anticancer prodrugs at specific sites/tissues. Phototherapy is a method that uses near-infrared (NIR) light to achieve local and non-invasive tumor therapy. The combination of chemotherapy and phototherapy has shown many therapeutic advantages, including synergistic therapeutic effects and the reduction of toxic and side effects of drugs through dose reduction. In this work, a hydrazone linkage was reported to conjugate Ti3C2Tx MXene nanosheets with doxorubicin hydrochloride (DOX) and methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) through a chemical surface modification to form a two-dimensional (2D) nano-prodrug Ti3C2Tx-DOX/PEG (TDP) for synergistic chemo-photothermal therapy. First, hydrazide functionalized Ti3C2Tx was obtained. Then, the carbonyl group of DOX and the aldehyde group of mPEG-CHO can form a pH-responsive hydrazone bond with hydrazide-functionalized Ti3C2Tx. The high surface area of Ti3C2Tx could overcome the reduced drug loading caused by conjugation. Aqueous stability and biocompatibility were enhanced by the introduction of PEG, making the material capable of prolonged circulation in the body’s bloodstream. By achieving excellent antitumor results with this nano-prodrug, we have added another brick to the edifice of Ti3C2Tx MXene as an anticancer drug carrier, and given new vitality to the study of anticancer prodrugs combined with nanotechnology.