Proteolysis targeting chimeras (PROTACs), heterobifunctional molecules that hijack the ubiquitin–proteasome system (UPS) to degrade specific proteins, hold great promise in treating diseases driven by traditionally “undruggable” targets. However, their large molecular weight, high hydrophobicity, and other physicochemical hurdles contribute to their limited bioavailability, suboptimal pharmacokinetics, and attenuated therapeutic efficacy. Consequently, diverse formulation innovations have been investigated to optimize PROTAC delivery. This review examines current challenges and advances in specialized drug delivery approaches designed to bolster PROTAC pharmacological performance. We first outline the fundamental limitations of PROTACs—their low aqueous solubility, poor cell permeability, rapid clearance, and concentration-dependent “hook effect”. We then discuss how various enabling formulations address these issues, including polymeric micelles, emulsions, amorphous solid dispersions, lipid-based nanoparticles, liposomes, and exosomes. Collectively, these delivery technologies substantially improve the therapeutic outcomes of PROTACs in preclinical cancer models. Future applications may extend beyond oncology to address other complex diseases using newly emerging heterobifunctional molecules. By integrating advanced formulation science with innovative degrader design, the field stands poised to unlock the clinical potential of PROTACs for protein degradation therapies.

Background/Objectives: Taxanes, including paclitaxel and docetaxel, are widely used in cancer treatment but frequently cause hypersensitivity reactions (HSRs), disrupting treatment continuity. This meta-analysis aimed to identify consistent risk factors for taxane-induced HSRs to support personalized risk assessments and optimize therapeutic outcomes. Methods: This systematic review and meta-analysis followed the PRISMA guidelines and was registered with PROSPERO (CRD42023476738). Comprehensive literature searches were conducted up to 30 June 2024. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Data were synthesized to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs), using fixed or random effects models. Results: A total of 18 studies of moderate or higher quality were included, involving 8333 patients. The incidence of HSRs ranged from 3.0% to 33.1%. Risk factors assessed included history of allergy, obesity, postmenopausal state, ovarian cancer, and H2 receptor antagonist (H2RA) premedication. A history of allergy was identified as a potential risk factor with marginal significance (OR 1.85, 95% CI 0.97–3.54, p = 0.06), while H2RA premedication, ovarian cancer, and female sex were not significantly associated with HSR risk. Substantial heterogeneity was observed for obesity (I² = 57.71%, p = 0.069) and postmenopausal status (I² = 78.98%). Conclusions: This study highlights the complex nature of taxane-induced HSRs and emphasizes the need for personalized risk assessments. While a history of allergy is a potential risk factor, heterogeneity across other factors underscores the importance of individualized approaches. Clinicians should tailor strategies to balance the benefits of taxane therapy with patient-specific risks to improve clinical outcomes.

Hyun Jin Park, Si Yoon Lee. R Clin Pharm 2025;3:28-35. https://doi.org/10.59931/rcp.25.0004

Introduction: The objective of this study was to evaluate the utilization and adherence of onsite clinics and identify the factors influencing them in semiconductor employees at risk of chronic diseases, including hypertension, diabetes, and dyslipidemia. Methods: A cross-sectional study was conducted through a retrospective review of electronic medical records from onsite clinics at a South Korean semiconductor company. The study focused on employees who visited the onsite clinics between 2013 and 2016 due to the risk of chronic diseases including hypertension, diabetes, and dyslipidemia. Descriptive statistics assessed clinic utilization and adherence, while multivariable logistic regression identified influencing factors, adjusted for age, sex, work type, work shift, workplace, specific onsite clinic, diagnosis, and disease duration. Results: Out of the 39,073 employees examined, 8,837 sought care at onsite clinics for managing chronic disease risks. The majority of these participants were male (88.2%) and predominantly aged in their 30s and 40s (84.6%). Among these individuals, 33.0% visited the clinics five or more times, and 28.5% filled prescriptions on two or more occasions. Chronic diseases were the second most common reason for onsite clinic visits. The average adherence to prescription as measured by the Proportion of Days Covered (PDC) was 0.61, with 40% of individuals showing a high adherence. Notably, older age and employment at workplaces located outside metropolitan areas were significant factors positively associated with both the utilization of onsite clinic services and adherence to prescribed treatments. Conclusion: This study found that onsite clinics within a semiconductor company were actively utilized for managing chronic diseases, particularly among older employees and those in workplaces located in areas where medical access is limited compared to metropolitan areas. These findings highlight the potential role of onsite clinics in enhancing chronic disease management. Future research across a broader range of workplaces could further support and expand these insights.