Drug Delivery Letters - Online First

The most prevalent type of dementia, Alzheimer's disease (AD), is typified by the presence of intracellular tau protein neurofibrillary tangles and extracellular amyloid plaques. There are currently about 50 million people who have dementia, and by 2030, that number is predicted to rise to 75 million, placing a significant financial strain on the nation's healthcare system. Novel disease-modifying treatments are desperately needed to combat this illness, given the consequences on patients' quality of life and the mounting financial strain. There are currently no disease-modifying medications available; instead, the majority of available therapies are symptomatic ones such as cholinesterase inhibitors and N-methyl-D-aspartate receptor blockers. The primary focus of therapeutic research against AD has shifted to tau-targeting strategies following multiple unsuccessful attempts to create medications against amyloidopathy. This article first provides an introduction to tauopathy in AD before summarizing current research on the creation of tau-oriented multi-target directed ligands and small compounds as therapies that target tau alteration, aggregation, and degradation. The overall goal of this work is to present a thorough and critical review of small compounds that are being investigated as potential treatment candidates for AD tauopathy.

Rectal Drug Delivery System (RDDS) emerges as an alternative administration route due to the rectum's small surface area and limited enzyme activity, which contribute to efficient drug absorption. RDDS offers various advantages, such as reduced first-pass metabolism, rapid absorption of low molecular weight drugs, and the ability to accommodate large retention volumes and facilitate absorption via the lymphatic system. Moreover, RDDS is preferable for drugs with low stability, solubility, and permeability via oral administration, as well as effectively addressing concerns related to gastric irritation or degradation. This review delves into the factors influencing drug absorption in RDDS, including drug properties, formulation types, and physiological and pathology-associated considerations. It further explores conventional RDDS, including enemas, suppositories, tablets, gels, sprays, ointments, and creams, as well as novel approaches involving nanoparticles, liposomes, microspheres, and solid lipid nanoparticles (SLNs) in rectal dosage forms. Furthermore, the challenges and prospects of RDDS in treating rectal diseases are discussed. This review provides valuable insights into the potential of RDDS, highlighting the importance of continuous research and development in enhancing patient outcomes and advancing healthcare practices.

Hydrogels are special materials that can hold a large amount of water and form 3D networks. In the past few years, there have been exciting improvements in hydrogel technology, bringing new ideas to many different areas. By trying out new materials like smart hydrogels that can respond to different conditions, provided new ways to deliver medicine precisely, build tissues, and create wearable gadgets. Among the most significant developments is the creation of smart hydrogels, which can react dynamically to different environmental stimuli. With their ability to release therapeutic chemicals under regulated conditions in response to particular physiological cues, these intelligent materials have enormous potential for the administration of precision medicine. These kinds of customized drug delivery systems have the power to completely change how treatments are administered by reducing adverse effects and increasing therapeutic efficacy. Hydrogels are also useful in tissue engineering, where they are used as scaffolds to create biological tissues that function. Hydrogel-based tissue constructions, which imitate the extracellular matrix, offer a favorable microenvironment for cell proliferation and differentiation, promoting the healing of injured or ill tissues. With its enormous potential in regenerative medicine, this revolutionary strategy offers hope for the treatment of ailments including organ failure. this article gives a thorough look at the recent developments in hydrogels, characterization techniques, and the new application of hydrogels in various fields of science.

In summary, new developments in hydrogel technology have opened up a plethora of opportunities in a variety of scientific fields. The adaptable properties of hydrogels continue to spur innovation in a variety of fields, including wearable technology, tissue engineering, and precision medicine. These applications offer revolutionary answers to urgent social issues.

Raloxifene hydrochloride belongs to the selective estrogen receptor modulator category. Initially, US FDA approved its use for the prevention and treatment of osteoporosis in post- menopausal women. Later, raloxifene hydrochloride was also approved for the prevention of invasive breast carcinoma in post-menopausal women under the high-risk category. Despite its immense and diverse therapeutic potential, the oral bioavailability of raloxifene hydrochloride is only ~ 2%. The factors responsible for the poor bioavailability of raloxifene hydrochloride include its amphiphobic nature, para-glycoprotein pump-mediated efflux in the intestine, and high pre-systemic glucuronidation. In the past two decades, multiple novel delivery systems, viz. lipid-based nanocarriers, polymeric nanoparticles, polymer-lipid hybrid nanoparticles, micelles, and mixed micelles, have been developed to overcome its drawbacks. Moreover, inclusion complex, phospholipid complex, and solid dispersion have also been developed to improve its solubility and dissolution rate. Further, some research groups successfully explored non-peroral routes like nasal and transdermal for augmenting the raloxifene hydrochloride bioavailability and its therapeutic efficacy. Hence, the principal objective of this review paper is to critically analyze all the delivery systems developed for raloxifene hydrochloride with their advantages and limitations. In addition, a detailed discussion of the physicochemical and pharmacokinetic parameters of raloxifene hydrochloride has been included in this paper. An in-depth understanding of these parameters will assist formulation scientists in developing efficient delivery systems in the future. In conclusion, the literature review revealed that the nanoparticulate systems successfully augmented the raloxifene hydrochloride bioavailability and therapeutic efficacy in pre-clinical experiments. However, future clinical trials should be conducted to assess their safety and therapeutic efficacy for rapid pre- clinical to clinical translation.