Injectable hydrogels (IHs) are smart biomaterials and are the most widely investigated and versatile technologies, which can be either implanted or inserted into living bodies with minimal invasion. Their unique features, tunable structure and stimuli-responsive biodegradation properties make these IHs promising in many biomedical applications, including tissue engineering, regenerative medicines, implants, drug/protein/gene delivery, cancer treatment, aesthetic corrections and spinal fusions. In this review, we comprehensively analyze the current development of several important types of IHs, including all those that have received FDA approval, are under clinical trials or are available commercially on the market. We also analyze the structural chemistry, synthesis, bonding, chemical/physical crosslinking and responsive release in association with current prospective research. Finally, we also review IHs’ associated future prospects, hurdles, limitations and challenges in their development, fabrication, synthesis, in situ applications and regulatory affairs.
Cancer remains a significant public health issue worldwide, standing as a primary contributor to global mortality, accounting for approximately 10 million fatalities in 2020
Solid-lipid nanoparticles (SLNs) are an innovative group of nanosystems used to deliver medicine to their respective targets with better efficiency and bioavailability in contrast to classical formulations. SLNs are less noxious, have fewer adverse effects, have more biocompatibility, and have easy biodegradability. Lipophilic, hydrophilic and hydrophobic drugs can be loaded into SLNs, to enhance their physical and chemical stability in critical environments. Certain antifungal agents used in different treatments are poorly soluble medications, biologicals, proteins etc. incorporated in SLNs to enhance their therapeutic outcome, increase their bioavailability and target specificity. SLNs-based antifungal agents are currently helpful against vicious drug-resistant fungal infections. This review covers the importance of SLNs in drug delivery of classical antifungal drugs, historical background, preparation, physicochemical characteristic, structure and sizes of SLNs, composition, drug entrapment efficacy, clinical evaluations and uses, challenges, antifungal drug resistance, strategies to overcome limitations, novel antifungal agents currently in clinical trials with special emphasis on fungal infections.
The purpose of this study was to assess the parameters of doxorubicin (DOX) loaded lipid polymer hybrid nanoparticles (LPHNs) formulation development, and then the bioavailability of DOX were determined in the rabbit model, in order to evaluate the intrinsic outcome of dosage form improvement after the oral administration. LPHNs were prepared by combine approach, using both magnetic stirring and probe sonication followed by its characterization in terms of size-distribution (Zeta Size), entrapment efficiency (EE), loading capacity, and the kinetics of DOX. LPHNPs were further characterized by using scanning electron microscopy (SEM), powder X-Ray diffractometry (P-XRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), in vitro and in vivo studies. The molecular modeling was determined through the density functional theory (DFT) simulations and interactions. DOX loaded and unloaded LPHNs were administered orally to the rabbits for bioavailability and pharmacokinetic parameters determinations. The plasma concentration of DOX was determined through high performance liquid chromatography (HPLC). The average size of DOX-loaded LPHNs was 121.90 ± 3.0 nm. The drug loading of DOX was 0.391% ± 0.01 of aqueous dispersion, where its encapsulation efficiency was 95.5% ± 1.39. After oral administration of the DOX-LPHNs, the area under the plasma drug concentration-time curve (AUC) improved about 2-folds comparatively (p < 0.05). DFT simulations were used to understand the interactions of polymers with different sites of DOX molecule. The larger negative binding energies (−9.33 to −18.53 kcal/mol) of the different complexes evince that the polymers have stronger affinity to bind with the DOX molecule while the negative values shows that the process is spontaneous, and the synthesis of DOX-LPHNs is energetically favorable. It was concluded that DOX-LPHNs provides a promising new formulation that can enhance the oral bioavailability, which have optimized compatibilities and improve the pharmacokinetic of DOX after oral administration.
In this study, gliclazide-loaded cubosomal particles were prepared for improving the oral bioavailability and antidiabetic activity of gliclazide. Four formulations of gliclazide-loaded cubosomal nanoparticles dispersions were prepared by the emulsification method using four different concentrations of glyceryl monooleate (GMO) and poloxamer 407 (P407) as the stabilizer. The prepared formulations were in vitro and in vivo evaluated. In vitro, the prepared gliclazide-loaded cubosomal dispersions exhibited disaggregated regular poly-angular particles with a nanometer-sized particle range from 220.60 ± 1.39 to 234.00 ± 2.90 nm and entrapped 73.84 ± 3.03 to 88.81 ± 0.94 of gliclazide. In vitro gliclazide release from cubosomal nanoparticles revealed an initially higher drug release during the first 2 h in acidic pH medium; subsequently, a comparatively higher drug release in alkaline medium relative to gliclazide suspension was observed. An in vivo absorption study in rats revealed a two-fold increase in the bioavailability of gliclazide cubosomal formulation relative to plain gliclazide suspension. Moreover, the study of in vivo hypoglycemic activity indicated that a higher percentage reduction in glucose level was observed after the administration of gliclazide cubosomal nanoparticles to rats. In conclusion, gliclazide-loaded cubosomal nanoparticles could be a promising delivery system for improving the oral absorption and antidiabetic activity of gliclazide.
Depression is a condition characterized by low mood and an aversion to activity, that causes behavioral problems, poor quality of life and limits daily life activities. It is considered as the fourth leading cause of disability worldwide. Selective Serotonin Reuptake Inhibitors (SSRIs) Monoamine Oxidase (MAO) inhibitors, Tricyclic Antidepressants (TCAs), and atypical antidepressants are some of the conventional medications used to treat depression. However, only about half of patients with major depressive disorder (MDD) respond effectively to first-line antidepressant therapy. Additionally, there are a number of drawbacks to standard antidepressants, such as anti-cholinergic side effects, drug-drug interactions, and food-drug interactions, which prompts researchers to look at alternative approaches to the treatment of depression. Medicinal plants and their metabolites are extensively tested for their efficacy against depression. Electronic databases such as Google scholar, Science Direct, SciFinder and PubMed were used to search relevant literature on the role of polyphenols in depression. Plants-derived Polyphenols represent a major class of compounds extensively distributed in plants. Number of polyphenols have demonstrated antidepressant activity, among which berberine, piperine, curcumin, naringenin, ascorbic acid and ginsenosides are extensively evaluated. The medicinal plants and their derived compounds mediated synthesized green nanoparticles have also exhibited considerable efficacy in the management of depression. The therapeutic effects of these phytochemicals is mediated via differentiation and inhibition of neuronal cell apoptosis, promotion of neuronal cell survival and modulation of key neurotransmitters. The aim of this study is to review compressively the chemical, pharmacological and neurological evidence showing the potential of polyphenols in depression.