<p>Improvement of Paclitaxel-Associated Adverse Reactions (ADRs) via the Use of Nano-Based Drug Delivery Systems: A Systematic Review and Network Meta-Analysis</p>

Abstract

Background: Paclitaxel is wildly used in chemotherapy, however, the adverse drug reactions (ADRs) occurred frequently. Various novel nano-based paclitaxel delivery systems were developed. The aim performed systemically review and meta-analyses to evaluate the effect adverse drug reactions (ADRs) of paclitaxel and its nano-based delivery systems. Methods: Systematically searched PubMed, Embase, Web of Science, Cochrane, Clinicalkey, Clinicaltrial.com, ASCO and ESMO. Data of adverse effect were analyzed to odds ratio (ORs) with 95% confidence interval (CI). The quality of studies was assessed with CASP Randomised Controlled Trial Checklist. Statistical analysis was used WinBUGS software (version 1.4.3) with the NetMetaXL interface (version 1.6.1). Results: Twenty-one studies, including 7011 patients and 6 paclitaxel formulations fulfilled the inclusion criteria. In all grade hypersensitivity reactions, comparing to SB-P, people with Lip-P had 0.19 times (95% CI= 0.02, 1.3) of chance, with Nab-P had 0.47 times (95% CI= 0.11, 1.40) of chance, with PPX had 0.44 times (95% CI= 0.03, 5.7) of chance for all grade adverse effect. In All grad neutropenia, comparing to Lip-P, people with SB-P had 0.83 times (95% CI= 0.15, 4.81) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.73 times (95% CI= 0.22, 2.42) of chance for all grade adverse effect. In leucopenia, comparing to Nab-P, people with SB-P had 0.66 times (95% CI= 0.50, 0.87) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.64 times (95% CI= 0.32, 1.16) of chance for all grade adverse effect. The rate of incidence in peripheral sensory neuropathy, myalgias and arthralgias tend to no significant differences between different formulations. Conclusion: Nano-based paclitaxel delivery resulted in fewer hypersensitivity reactions than solvent-based delivery. However, the incidence of neutropenia and leucopenia was higher in nano-based than solvent-based paclitaxel delivery. Dose-dependent ADRs were more frequent in paclitaxel anticancer treatment.

Targeted Oral Delivery of Paclitaxel Using Colostrum-Derived Exosomes

“…Clinical translatability of new drugs or nanoformulations are often limited due to toxicity concerns at various stages of drug discovery and development. While efficacious, PAC is generally not well tolerated and its limitations include low solubility, and significant toxicity associated with both the drug and the solvent (Cremophor EL), including hypersensitivity reactions, bronchospasms, hypotension, hematological toxicity, periph-eral sensory neuropathy, myalgia, arthralgia and alopecia [8,45]. We have demonstrated FA-ExoPAC clearly enhanced therapeutic efficacy of PAC diminishing the dose-related toxicity issues.…”

“…As with many other chemo drugs, PAC exhibits poor oral bioavailability; hence, it is administered intravenously. To increase bioavailability, several drug delivery formulations of PAC have been developed, including nanoparticle albumin-bound (Abraxane ® ), liposomal (Lipusu ® ), polymeric micelles (Genexol ® PM), polymeric-drug conjugates (Xyotax™/OPAXIO) and an injection concentrate for nanodispersion (Taclantis™/Bevetex ® ), as reviewed by Chor et al [8]. Clinical translatability of these nanoformulations was impeded due to various factors like toxicity, scalability and cost.…”

“…To overcome these unfavorable physicochemical and pharmacokinetic properties of PAC, several additional delivery approaches have been attempted [8]. Toxicity limitations of solvent-based carriers can be overcome by using nanovesicles derived from natural sources such as milk [9,10].…”

Heptamethine Cyanine Dye MHI-148-Mediated Drug Delivery System to Enhance the Anticancer Efficiency of Paclitaxel

“…The conjugation of MHI-148 and PTX is based on a solution-phase reaction carried out between the 2′-OH group of PTX and the carboxylic group of MHI-148, in the presence of DIC and DMAP as activating agents, forming a stable 33 , 34 ester linkage ( Figure 1A ). The purification and effectual removal of unconjugated MHI-148 and PTX were performed via dialysis using the Mini Dialysis membrane (MWCO cut off 1k) in triple-distilled water for 2 days.…”

Breast cancer: Muscarinic receptors as new targets for tumor therapy

“…Despite the extended use of paclitaxel in anti-tumor treatment, it has been reported that its administration at therapeutic concentrations (10 -6 mol/L approximately) causes adverse effects like hepatotoxicity, leukopenia, neutropenia, anemia, thrombocytopenia, neurotoxicity, vomits, alopecia, fatigue, mucositis and diarrhea[ 155 - 158 ]. In addition to the low-efficiency synthesis of paclitaxel and its side effects, another problem is its insolubility in water, which affects its bioavailability.…”