Emerging frontiers in nanomedicine targeted therapy for prostate cancer.

Prostate cancer is a prevalent cancer in men, often treated with chemotherapy. However, it tumor cells are clinically grows slowly and is heterogeneous, leading to treatment resistance and recurrence. Nanomedicines, through targeted delivery using nanocarriers, can enhance drug accumulation at the tumor site, sustain drug release, and counteract drug resistance. In addition, combination therapy using nanomedicines can target multiple cancer pathways, improving effectiveness and addressing tumor heterogeneity. The application of nanomedicine in prostate cancer treatment would be an important strategy in controlling tumor dynamic process as well as improve survival. Thus, this review highlights therapeutic nanoparticles as a solution for prostate cancer chemotherapy, exploring targeting strategies and approaches to combat drug resistance.

Improving the Emergency Department Management of Sickle Cell Vaso-Occlusive Pain Crisis: The Role and Options of Sublingual and Intranasally Administered Analgesia.

Vaso-occlusive crisis (VOC), characterized by periods of excruciating pain is the most common clinical manifestation of sickle cell disease (SCD), often resulting in emergency room presentation. These patients often experience long wait times in the emergency department before receiving their first dose of analgesia. This delay results from the complexities of the emergency care system. Using the intranasal or sublingual approach to administering analgesia to SCD patients with VOC offers a fast, safe, noninvasive, atraumatic, and easily accessible route of administration which could reduce the time to first dose of analgesia. With the evolving advances in the development and delivery of analgesic medications, providers should be conversant with the nuances of intranasal and sublingual analgesia in the management of acute vaso-occlusive pain crisis. This review explores the pharmacokinetic profiles, dosages, and administration of intranasal and sublingual analgesics with relevance to the SCD population.

Approaches to Improve Macromolecule and Nanoparticle Accumulation in the Tumor Microenvironment by the Enhanced Permeability and Retention Effect.

Passive targeting is the foremost mechanism by which nanocarriers and drug-bearing macromolecules deliver their payload selectively to solid tumors. An important driver of passive targeting is the enhanced permeability and retention (EPR) effect, which is the cornerstone of most carrier-based tumor-targeted drug delivery efforts. Despite the huge number of publications showcasing successes in preclinical animal models, translation to the clinic has been poor, with only a few nano-based drugs currently being used for the treatment of cancers. Several barriers and factors have been adduced for the low delivery efficiency to solid tumors and poor clinical translation, including the characteristics of the nanocarriers and macromolecules, vascular and physiological barriers, the heterogeneity of tumor blood supply which affects the homogenous distribution of nanocarriers within tumors, and the transport and penetration depth of macromolecules and nanoparticles in the tumor matrix. To address the challenges associated with poor tumor targeting and therapeutic efficacy in humans, the identified barriers that affect the efficiency of the enhanced permeability and retention (EPR) effect for macromolecular therapeutics and nanoparticle delivery systems need to be overcome. In this review, approaches to facilitate improved EPR delivery outcomes and the clinical translation of novel macromolecular therapeutics and nanoparticle drug delivery systems are discussed.