Design and Characterisation of pH-Responsive Photosensitiser-Loaded Nano-Transfersomes for Enhanced Photodynamic Therapy

Photodynamic therapy (PDT) is a non-invasive and tumour-specific therapy. Photosensitizers (PSs) (essential ingredients in PDT) aggregate easily owing to their lipophilic properties. The aim of this study was to synthesise a PS (methyl pheophorbide a, MPa) and design a biocompatible lipid-based nanocarrier to improve its bioavailability and pharmacological effects. MPa-loaded nano-transfersomes were fabricated by sonication. The characteristics of synthesised PS and nano-transfersomes were assessed. The effects of PDT were evaluated by 1,3-diphenylisobenzofuran assay and by measuring photo-cytotoxicity against HeLa and A549 cell lines. The mean particle size and zeta potential for nano-transfersomes ranged from 95.84 to 267.53 nm and −19.53 to −45.08 mV, respectively. Nano-transfersomes exhibited sustained drug release for 48 h in a physiological environment (as against burst release in an acidic environment), which enables its use as a pH-responsive drug release system in PDT with enhanced photodynamic activity and reduced side effects. The formulations showed light cytotoxicity, but no dark toxicity, which meant that light irradiation resulted in anti-cancer effects. Additionally, formulations with the smallest size exhibited photodynamic activity to a larger extent than those with the highest loading capacity or free MPa. These results suggest that our MPa-loaded nano-transfersome system is a promising anti-cancer strategy for PDT.

3D bioprinted scaffolds for diabetic wound-healing applications

The treatment strategy required for the effective healing of diabetic foot ulcer (DFU) is a complex process that is requiring several combined therapeutic approaches. As a result, there is a significant clinical and economic burden associated in treating DFU. Furthermore, these treatments are often unsuccessful, commonly resulting in lower-limb amputation. The use of drug-loaded scaffolds to treat DFU has previously been investigated using electrospinning and fused deposition modelling (FDM) 3D printing techniques; however, the rapidly evolving field of bioprinting is creating new opportunities for innovation within this research area. In this study, 3D-bioprinted scaffolds with different designs have been fabricated for the delivery of an antibiotic (levoflocixin) to DFU. The scaffolds were fully characterised by a variety of techniques (e.g. SEM, DSC/TGA, FTIR, and mechanical characterisation), demonstrating excellent mechanical properties and providing sustained drug release for 4 weeks. This proof of concept study demonstrates the innovative potential of bioprinting technologies in fabrication of antibiotic scaffolds for the treatment of DFU. Graphical abstract

FORMULATION AND EVALUATION OF BESIFLOXACIN NON-ERODIBLE OCULAR INSERTS

Objective: Ocular inserts offer many advantages over conventional dosage forms, like increased ocular residence, the possibility of releasing a drug at a slow and constant rate, accurate dosing, exclusion of preservatives, and increased shelf life. Besifloxacin is a very important drug for the treatment of infectious conjunctivitis. The present study was aimed to formulate and evaluate Besifloxacin Non-Erodible Ocular Insert using Pullulan and polyvinyl pyrrolidone as a drug reservoir, PEG 400 as a plasticizer, and Eudragit RS-100 as a rate-controlling membrane. Methods: Central composite design was employed to study the effect of independent variables, i.e., effects of Pullulan amount (X1) and PVP (X2) on the dependent variables, i.e., % moisture absorption and In vitro diffusion rate. After evaluation of all thirteen batches of ocular insert reservoir formulation, BSF2 and BSF4 were selected as a satisfactory formulation and was sandwiched between rate-controlling membrane, which was made up of Eudragit RS-100 (3 and 5%). Results: The drug content of all formulations was found to be in the range of 95.33 to 99.89 %. In vitro diffusion of Besifloxacin from reservoir formulations (BSF1 to BSF13) was found to be 62.44 to 70.62 %. In vitro diffusion rate of an ocular insert of Besifloxacin can offer benefits such as increasing residence time, prolonging drug release in the eye for 24 h. Eudragit RS-100, as a sustained drug release polymer, showed promising sustained released action. Conclusion: The study concluded that Besifloxacin non-erodible ocular inserts can be successfully developed using Pullulan and polyvinyl pyrrolidone, which will sustain the release of the drug also reduce the frequency of administration, and thereby may help to improve patient compliance.

Application of Nanomaterial in Hydrogels Related to Wound Healing

Traditional dressings used for wound repair, such as gauze, have shortcomings; for example, they cannot provide a suitable microenvironment for wound recovery. Therefore, it is necessary to find a better dressing to overcome shortcomings. Hydrogel provides a suitable wet environment, has good biocompatibility, and has a strong swelling rate to absorb exudate. Nanomaterial in hydrogels has been used to improve their performance and overcome the shortcomings of current hydrogel dressings. Hydrogel dressing can also be loaded with nanodrug particles to exert a better therapeutic effect than conventional drugs and to make the dressing more practical. This article reviews the application of nanotechnology in hydrogels related to wound healing and discusses the application prospects of nanohydrogels. After searching for hydrogel articles related to wound healing, we found that nanomaterial can not only enhance the mechanical strength, antibacterial properties, and adhesion of hydrogels but also achieve sustained drug release. From the perspective of clinical application, these characteristics are significant for wound healing. The combination of nanomaterial and hydrogel is an ideal dressing with broad application prospects for wound healing in the future.

The Effect of Electrospun Dihydroartemisinin-Loaded Polycaprolactone/Collagen Scaffolds On Osteoblastic Differentiation of Human Adipose-Derived Stem Cells

In this study, Dihydroartemisinin (DHART)-loaded polycaprolactone collagen nanofibers (PCL/Col NFs) were constructed as effective biocompatible scaffolds through adjusting the proportions of hydrophobic/ hydrophilic polymers for enhanced osteoblastic differentiation of human adipose-derived stem cells (hADSCs). The designed NFs were characterized through FTIR, XRD, TGA, FE-SEM, and tensile testing. DHART-loaded PCL/Col electrospun NFs provide an ideal solution, with the potential of sustained drug release as well as inhibition of drug re-crystallization. Interestingly, inhibiting DHART re-crystallization can improve its bioavailability, providing a more effective therapeutic efficacy. Besides, the data set found through FE-SEM, MTT, PicoGreen, qPCR, and alkaline phosphatase (ALP) assays revealed the improved adhesion and proliferation rate of hADSCs cultured on PCL/Col/DHART (5%) NFs after 14 and 21 days of incubation. These findings confirmed the potential of the designed NF scaffolds for sustained/controlled release of DHART therapeutic molecules toward bone tissue regeneration and engineering.

Retrovirus Drugs-Loaded PEGylated PAMAM for Prolonging Drug Release and Enhancing Efficiency in HIV Treatment

Polyamidoamine dendrimer (PAMAM) with its unique characteristics emerges as a potential drug delivery system which can prolong releasing time, reduce the side effects but still retaining treatment efficiency. In this study, methoxy polyethylene glycol modified PAMAM generation 3.0 (G3.0@mPEG) is prepared and characterized via 1H-NMR, FT-IR, and TEM. Subsequently, two antiretroviral agents (ARV) including lamivudine (3TC) and zidovudine (AZT) are individually encapsulated into G3.0@mPEG. The drug-loading efficiency, drug release profile, cytotoxicity and anti-HIV activity are then evaluated. The results illustrate that G3.0@mPEG particles are spherical with a size of 34.5 ± 0.2 nm and a drug loading content of about 9%. Both G3.0@mPEG and [email protected]@mPEG show no cytotoxicity on BJ cells, and G3.0@mPEG loading 3TC and AZT performs sustained drug release behavior which is best fitted with the Korsmeyer–Peppas model. Finally, the anti-HIV activity of ARV via Enzymatic Assay of Pepsin is retained after being loaded into the G3.0@mPEG, in which about 36% of pepsin activity was inhibited by AZT at the concentration of 0.226 mM. Overall, PAMAM G3.0@mPEG is a promising nanocarrier system for loading ARV in HIV treatment and prevention.

Camptothecin-Carrying Cuco2s4 Nanoparticles: Sustained Drug Release And Anticancer Activity

Nanocarriers of anticancer drugs are delicately designed with precision addition at every attempt. In this paper, we report CuCo2S4 nanoparticles that show light-absorption in the NIR-II wavelength range and possess magnetic characteristics. The synthesized nanoparticles are characterized employing XRD, SEM, DLS, TGA, and XPS methods. The nanoparticles form a composite with biocompatible polymeric β-cyclodextrin. The nanoparticles possess a band gap energy of 2.25 eV. The magnetic property arises due to the cobalt-incorporation in the nanoparticles. The anticancer drug, camptothecin, is loaded in the nanocarrier with an 89% adsorption efficiency. The in vitro release of the drug occurs in a sustained fashion. Further, the in vitro anticancer potential of the nanocarrier is examined on breast cancer (MDA=MB-231) cell lines and the activities of the free- and the drug-loaded nanocarrier are compared. The cobalt-containing copper sulfide nanoparticle-poly-β-cyclodextrin composite works as a promising nanocarrier of camptothecin.

Nitric Oxide-Releasing Bacterial Cellulose/Chitosan Crosslinked Hydrogels for the Treatment of Polymicrobial Wound Infections

Polymicrobial wound infections are a major cause of infectious disease-related morbidity and mortality worldwide. In this study, we prepared a nitric oxide (NO)-releasing oxidized bacterial cellulose/chitosan (BCTO/CHI) crosslinked hydrogel to effectively treat polymicrobial wound infections. Linear polyethyleneimine diazeniumdiolate (PEI/NO) was used as the NO donor. The aldehyde group of BCTO and the amine of CHI were used as crosslinked hydrogel-based materials; their high NO loading capacity and antibacterial activity on the treatment of polymicrobial-infected wounds were investigated. The blank and NO-loaded crosslinked hydrogels, namely BCTO-CHI and BCTO-CHI-PEI/NO, were characterized according to their morphologies, chemical properties, and drug loading. BCTO-CHI-PEI/NO exhibited sustained drug release over four days. The high NO loading of BCTO-CHI-PEI/NO enhanced the bactericidal efficacy against multiple bacteria compared with BCTO-CHI. Furthermore, compared with blank hydrogels, BCTO-CHI-PEI/NO has a favorable rheological property due to the addition of a polymer-based NO donor. Moreover, BCTO-CHI-PEI/NO significantly accelerated wound healing and re-epithelialization in a mouse model of polymicrobial-infected wounds. We also found that both crosslinked hydrogels were nontoxic to healthy mammalian fibroblast cells. Therefore, our data suggest that the BCTO-CHI-PEI/NO developed in this study improves the efficacy of NO in the treatment of polymicrobial wound infections.

Therapeutic Applications of Halloysite

In recent years, nanomaterials have attracted significant research interest for applications in biomedicine. Many kinds of engineered nanomaterials, such as lipid nanoparticles, polymeric nanoparticles, porous nanomaterials, silica, and clay nanoparticles, have been investigated for use in drug delivery systems, regenerative medicine, and scaffolds for tissue engineering. Some of the most attractive nanoparticles for biomedical applications are nanoclays. According to their mineralogical composition, approximately 30 different nanoclays exist, and the more commonly used clays are bentonite, halloysite, kaolinite, laponite, and montmorillonite. For millennia, clay minerals have been extensively investigated for use in antidiarrhea solutions, anti-inflammatory agents, blood purification, reducing infections, and healing of stomach ulcers. This widespread use is due to their high porosity, surface properties, large surface area, excellent biocompatibility, the potential for sustained drug release, thermal and chemical stability. We begin this review by discussing the major nanoclay types and their application in biomedicine, focusing on current research areas for halloysite in biomedicine. Finally, recent trends and future directions in HNT research for biomedical application are explored.