Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with unmet medical need, and is the leading cause of age-related dementia affecting millions of people worldwide. This work aims at developing small, high-drug loading capacity (DL) and -entrapment efficiency (EE) memantine hydrochloride (MEM)/chitosan nanocrystals (CS-NCs) to treat moderate to severe dementia associated with AD. MEM-loaded chitosan nanocrystals (MEM/CS-NCs, further abbreviated as MEM-NCs) were prepared by the ionic gelation method. Different formulations were prepared by varying the concentrations of CS and sodium tripolyphosphate (STPP). The prepared MEM-NCs formulations (n = 8) were evaluated for their particle size (PS), polydispersibility index (PDI), zeta potential (ZP), DL, EE and characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, in vitro (i.e., release behavior, cytotoxicity) and ex vivo studies (i.e., histopathology) studies were carried out. The results show that the DL was over 92% and the EE was higher than 73%, while the particles were relatively small with nanometric PS (152.63 ± 12.95 to 310.23 ± 10.49 nm), uniform with acceptable PDI (0.336 ± 0.05 to 0.534 ± 0.02), and stable with positive ZP (23.8 ± 0.4 mV to 54.0 ± 0.5 mV). The optimal formulation (MEM-NC3) was selected mainly based on the PS (152.63 ± 12.95 nm), DL (98.44 ± 3.31%), and EE (78.7 ± 3.11%). Interestingly, it does not elicit any cytotoxic and tissue damage when examining at goat nasal mucosa. The selected formulation was subjected to surface morphological studies such as transmission electron microscopy (TEM), which revealed that the NCs were spherical in shape and small (100 nm). Interestingly, the selected formulation was able to sustain the drug release for up to 24 h with an initial burst release (86.51 %). We conclude that the prepared MEM-NCs represent a promising drug formulation for further in vivo studies (in animal models and in a clinical setting) to prevent and treat AD.

This narrative review summarizes recent advances in in situ gel drug delivery systems for periodontal therapy, focusing on formulation strategies, the pharmaceutical agents involved, and their clinical applications. A comprehensive search was conducted on PubMed, Scopus, and Google Scholar for English-language articles published from 2000 to 2024 using relevant keywords. Articles were selected based on their clinical significance, scientific rigor, and relevance to periodontal treatment. In situ gels use physiological stimuli such as pH, temperature, or ions for sol-to-gel transition, enabling sustained and localized drug release into periodontal pockets. These systems aim to improve therapeutic efficacy and reduce systemic side effects. However, limitations like inconsistent gelation, low mechanical strength, and limited long-term clinical data hinder widespread clinical adoption. Future research should focus on formulation optimization and rigorous clinical trials to facilitate the integration of in-situ gels into routine periodontal care.

Headache serves as a prevalent symptom across various diseases and disorders, with migraines notably exerting a substantial impact on an individual's daily well-being and occupational functionality. Immediate management of migraines assumes pivotal significance due to the prolonged and debilitating nature of associated symptoms. Migraines commonly manifest in two forms: migraine with aura and migraine without aura. Afflicted individuals often contend with enduring symptoms such as phonophobia, photophobia, and manifestations akin to vomiting. Traditional medications necessitate a protracted timeframe, often exceeding 1-2 hours, for alleviating pain induced by migraines. The innovative approach of nose-to-brain drug delivery emerges as a promising strategy in addressing neurological conditions, offering the advantage of mitigating undesired side effects compared to conventional pharmaceutical interventions. By specifically targeting the olfactory and trigeminal nerves, this method circumvents the Blood-Brain-Barrier (BBB), thereby yielding more favorable therapeutic outcomes. Although diverse nano formulations have been developed, the concept of nano inhalable dry powder stands out as an optimal modality for migraine treatment. This comprehensive review encapsulates the existing pharmacotherapeutic landscape for migraine treatment, delving into the diverse modalities employed in the development of dry powder formulations, elucidating their inherent advantages, and contemplating the future trajectory of nano-inhalable dry powder applications in migraine therapeutics.

1. From the global cancer statistics, it is estimated that 20 million, out of these new instances were identified in 2022, which led to 9.7 million deaths due to different types of cancers [1]. Bre...