Lancasterlester2380

The studied techniques did not produce significant histological alterations after their application, except for an observed increase in Langerhans cells and melanocytes after applying electroporation, and an epidermal thinning after using microneedles, with variable results regarding dermal thickness. Although all the studied barrier disruptors can accomplish transdermal delivery, the best disruptor is dependent on the particular molecule.Co-precipitation is an emerging method to generate amorphous solid dispersions (ASDs), notable for its ability to enable the production of ASDs containing pharmaceuticals with thermal instability and limited solubility. As is true for spray drying and other unit operations to generate amorphous materials, changes in processing conditions during co-precipitation, such as solvent selection, can have a significant impact on the molecular and bulk powder properties of co-precipitated amorphous dispersions (cPAD). Using posaconazole as a model API, this work investigates how solvent selection can be leveraged to mitigate crystallization and maximize bulk density for precipitated amorphous dispersions. A precipitation process is developed to generate high-bulk-density amorphous dispersions. Insights from this system provide a mechanistic rationale to control the solid-state and bulk powder properties of amorphous dispersions.Nucleic acid-based therapeutics have demonstrated their efficacy in the treatment of various diseases and vaccine development. Antisense oligonucleotide (ASO) technology exploits a single-strand short oligonucleotide to either cause target RNA degradation or sterically block the binding of cellular factors or machineries to the target RNA. Chemical modification or bioconjugation of ASOs can enhance both its pharmacokinetic and pharmacodynamic performance, and it enables customization for a specific clinical purpose. ASO-based therapies have been used for treatment of genetic disorders, cancer and viral infections. In particular, ASOs can be rapidly developed for newly emerging virus and their reemerging variants. This review discusses ASO modifications and delivery options as well as the design of antiviral ASOs. A better understanding of the viral life cycle and virus-host interactions as well as advances in oligonucleotide technology will benefit the development of ASO-based antiviral therapies.For the treatment of neurological diseases, achieving sufficient exposure to the brain parenchyma is a critical determinant of drug efficacy. The blood-brain barrier (BBB) functions to tightly control the passage of substances between the bloodstream and the central nervous system, and as such poses a major obstacle that must be overcome for therapeutics to enter the brain. Monoclonal antibodies have emerged as one of the best-selling treatment modalities available in the pharmaceutical market owing to their high target specificity. However, it has been estimated that only 0.1% of peripherally administered antibodies can cross the BBB, contributing to the low success rate of immunotherapy seen in clinical trials for the treatment of neurological diseases. The development of new strategies for antibody delivery across the BBB is thereby crucial to improve immunotherapeutic efficacy. Here, we discuss the current strategies that have been employed to enhance antibody delivery across the BBB. These include (i) focused ultrasound in combination with microbubbles, (ii) engineered bi-specific antibodies, and (iii) nanoparticles. Furthermore, we discuss emerging strategies such as extracellular vesicles with BBB-crossing properties and vectored antibody genes capable of being encapsulated within a BBB delivery vehicle.

Tacrolimus (TAC) is a drug of natural origin used in conventional topical dosage forms to control atopic dermatitis. However, direct application of the drug often causes adverse side effects in some patients. Hence, drug nanoencapsulation could be used as an improved novel therapy to mitigate the adverse effects and enhance bioavailability of the drug.

Physicochemical properties, in vitro drug release experiments, and in vivo anti-inflammatory activity studies were performed.

TAC-loaded nanocapsules were successfully prepared by the interfacial deposition of preformed polymer using poly(ε-caprolactone) (PCL). The nanoparticulate systems presented a spherical shape with a smooth and regular surface, adequate diameter (226 to 250 nm), polydispersity index below 0.3, and suitable electrical stability (-38 to -42 mV). X-ray diffraction confirmed that the encapsulation method provided mainly the drug molecular dispersion in the nanocapsule oily core. Fourier-transform infrared spectra suggested that nanoencapsulation did not result in chemical bonds between drug and polymer. In vitro drug dissolution experiments showed a controlled release with a slight initial burst. The release kinetics showed zero-order kinetics. As per the Korsmeyer-Peppas model, anomalous transport features were observed. TAC-loaded PCL nanocapsules exhibited excellent anti-inflammatory activity when compared to the free drug.

TAC-loaded PCL nanocapsules can be suitably used as a novel nano-based dosage form to control atopic dermatitis.

TAC-loaded PCL nanocapsules can be suitably used as a novel nano-based dosage form to control atopic dermatitis.Many dermatological conditions, such as eczema and psoriasis, are treated with topical therapeutic products. Instead of applying the active drug directly onto the skin, it is combined with a vehicle to aid in its delivery across the stratum corneum (SC) and into deeper regions of the skin, namely the epidermis and dermis. Absorption into the systemic circulation is minimized. Topical vehicles are also used as cosmetic moisturizers (often termed emollient therapy) to ameliorate dry skin, which is a cornerstone of the management of various dermatological conditions, including xerosis, eczema, psoriasis, and aging. The most common topical vehicles include ointments, creams, gels, and lotions, among others. It is crucial that topical vehicles are chosen based upon the size and properties (wet/dry, mucous/non-mucous, healthy/diseased) of the skin to be treated in order to optimize application and contact of the product with the skin, as this can have profound impacts on potency, efficacy, and patient compliance. This review examines common topical vehicles used for drug delivery and cosmetic moisturizers, including their formulation, advantages and disadvantages, and effects on the skin. The unique rules imposed by governing regulatory bodies in Australia and around the world, in terms of topical product claims, are also briefly examined.Fungal keratitis is a serious clinical infection on the cornea caused by fungi and is one of the leading causes of blindness in Asian countries. The treatment options are currently limited to a few antifungal agents. With the increasing incidence of drug-resistant infections, many patients fail to respond to antibiotics. Riboflavin-mediated corneal crosslinking (similar to photodynamic therapy (PDT)) for corneal ectasia was approved in the US in the early 2000s. Current evidence suggests that PDT could have the potential to inhibit fungal biofilm formation and overcome drug resistance by using riboflavin and rose bengal as photosensitizers. However, only a few clinical trials have been initiated in anti-fungal keratitis PDT treatment. Moreover, the removal of the corneal epithelium and repeated application of riboflavin and rose bengal are required to improve drug penetration before and during PDT. Thus, an improvement in trans-corneal drug delivery is mandatory for a successful and efficient treatment. In this article, we review the studies published to date using PDT against fungal keratitis and aim to enhance the understanding and awareness of this research area. The potential of modifying photosensitizers using nanotechnology to improve the efficacy of PDT on fungal keratitis is also briefly reviewed.The purpose of this study was to design, for the first time, a co-loaded liposomal formulation (CLL) for treatment of glaucoma including timolol maleate (TM) in the lipid bilayer and acetazolamide (Acz)-(2-hydroxy)propyl β-cyclodextrin (HPβCD) complexes (AczHP) solubilized in the aqueous core of liposomes. Formulations with TM (TM-L) and AczHP (AczHP-L), separately, were also prepared and characterized. learn more A preliminary study comprising the Acz/HPβCD complexes and their interaction with cholesterol (a component of the lipid bilayer) was realized. Then, a screening study on formulation factors affecting the quality of the product was carried out following the design of the experiment methodology. In addition, in vitro release and permeation studies and in vivo lowering intraocular pressure (IOP) studies were performed. The results of the inclusion complexation behavior, characterization, and binding ability of Acz with HPβCD showed that HPβCD could enhance the water solubility of Acz despite the weak binding ability of the complex. Ch disturbed the stability and solubility parameters of Acz due to the fact of its competence by CD; thus, Chems (steroid derivative) was selected for further liposome formulation studies. The optimization of the lipid bilayer composition (DDAB, 0.0173 mmol and no double loading) and the extrusion as methods to reduce vesicle size were crucial for improving the physico-chemical properties and encapsulation efficiency of both drugs. In vitro release and permeation studies demonstrated that the CLL formulation showed improvement in in vitro drug release and permeation compared to the liposomal formulations with a single drug (TM-L and AczHP-L) and the standard solutions (TM-S and AczHP-S). CLL showed high efficacy in reducing and prolonging IOP, suggesting that the synergistic effect of TM and Acz on aqueous humor retention and the presence of this cyclodextrin and liposomes as permeation enhancers are responsible for the success of this strategy of co-loading for glaucoma therapy.A transcriptome-wide analysis of human liver for demonstrating differences between young and old humans has not yet been performed. However, identifying major age-related alterations in hepatic gene expression may pinpoint ontogenetic shifts with important hepatic and systemic consequences, provide novel pharmacogenetic information, offer clues to efficiently counteract symptoms of old age, and improve the overarching understanding of individual decline. Next-generation sequencing (NGS) data analyzed by the Mann-Whitney nonparametric test and Ensemble Feature Selection (EFS) bioinformatics identified 44 transcripts among 60,617 total and 19,986 protein-encoding transcripts that significantly (p = 0.0003 to 0.0464) and strikingly (EFS score > 0.316 transcripts; EFS score > 0.228 transcripts) differ between young and old livers. Most of these age-related transcripts were assigned to the categories 'regulome', 'inflammaging', 'regeneration', and 'pharmacogenes'. NGS results were confirmed by quantitative real-time polymerase chain reaction. Our results have important implications for the areas of ontogeny/aging and the age-dependent increase in major liver diseases. Finally, we present a broadly substantiated and testable hypothesis on a genetically governed 'aging cascade', wherein PPP1R10 acts as a putative ontogenetic master regulator, prominently flanked by IGFALS and DUSP1. This transcriptome-wide analysis of human liver offers potential clues towards developing safer and improved therapeutic interventions against major liver diseases and increased insights into key mechanisms underlying aging.