Drug Delivery最新文献

{"title":"Chitosan-coated bovine serum albumin nanoparticles for topical tetrandrine delivery in glaucoma: <i>in vitro</i> and <i>in vivo</i> assessment.","authors":"Salma El-Sayed Radwan, Riham M El-Moslemany, Radwa A Mehanna, Eman H Thabet, Elsayeda-Zeinab A Abdelfattah, Amal El-Kamel","doi":"10.1080/10717544.2022.2058648","DOIUrl":"10.1080/10717544.2022.2058648","url":null,"abstract":"<p><p>Glaucoma is one of the leading causes of blindness. Therapies available suffer from several drawbacks including low bioavailability, repeated administration and poor patient compliance with adverse effects thereafter. In this study, bovine serum albumin nanoparticles (BSA-NPs) coated with chitosan(CS) were developed for the topical delivery of tetrandrine (TET) for glaucoma management. Optimized nanoparticles were prepared by desolvation. pH, BSA, CS and cross-linking agent concentrations effects on BSA-NPs colloidal properties were investigated. CS-BSA-NPs with particle size 237.9 nm and zeta potential 24 mV was selected for further evaluation. EE% exceeded 95% with sustained release profile. In vitro mucoadhesion was evaluated based on changes in viscosity and zeta potential upon incubation with mucin. <i>Ex vivo</i> transcorneal permeation was significantly enhanced for CS coated formulation. <i>In vitro</i> cell culture studies on corneal stromal fibroblasts revealed NPs biocompatibility with enhanced cellular uptake and improved antioxidant and anti-proliferative properties for the CS-coated formulation. Moreover, BSA-NPs were nonirritant as shown by HET-CAM test. Also, bioavailability in rabbit aqueous humor showed 2-fold increase for CS-TET-BSA-NPs compared to TET with a sustained reduction in intraocular pressure in a rabbit glaucoma model. Overall, results suggest CS-BSA-NPs as a promising platform for topical ocular TET delivery in the management of glaucoma.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"1150-1163"},"PeriodicalIF":6.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004496/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49082440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting interleukin-13 receptor α2 (IL-13Rα2) for glioblastoma therapy with surface functionalized nanocarriers.","authors":"Ruijia Liang,&nbsp;Cheng Wu,&nbsp;Shiming Liu,&nbsp;Wenyan Zhao","doi":"10.1080/10717544.2022.2075986","DOIUrl":"10.1080/10717544.2022.2075986","url":null,"abstract":"Abstract Despite surgical and therapeutic advances, glioblastoma multiforme (GBM) is among the most fatal primary brain tumor that is aggressive in nature. Patients with GBM have a median lifespan of just 15 months when treated with the current standard of therapy, which includes surgical resection and concomitant chemo-radiotherapy. In recent years, nanotechnology has shown considerable promise in treating a variety of illnesses, and certain nanomaterials have been proven to pass the blood–brain barrier (BBB) and stay in glioblastoma tissues. Recent preclinical research suggests that the diagnosis and treatment of brain tumor is significantly explored through the intervention of nanomaterials that has showed enhanced effect. In order to elicit an antitumor response, it is necessary to retain the therapeutic candidates within glioblastoma tissues and this job is effectively carried out by nanocarrier particularly functionalized nanocarriers. In the arena of neoplastic diseases including GBM have achieved great attention in recent decades. Furthermore, interleukin-13 receptor α chain variant 2 (IL13Rα2) is a highly expressed and studied target in GBM that is lacked by the surrounding environment. The absence of IL13Rα2 in surrounding normal tissues has made it a suitable target in glioblastoma therapy. In this review article, we highlighted the role of IL13Rα2 as a potential target in GBM along with design and fabrication of efficient targeting strategies for IL13Rα2 through surface functionalized nanocarriers.","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"1620-1630"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47064451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization of mirtazapine loaded into mesoporous silica nanostructures via Box-Behnken design: <i>in-vitro</i> characterization and <i>in-vivo</i> assessment.","authors":"Abeer A Musallam,&nbsp;M A Mahdy,&nbsp;Hanan M Elnahas,&nbsp;Reem A Aldeeb","doi":"10.1080/10717544.2022.2075985","DOIUrl":"https://doi.org/10.1080/10717544.2022.2075985","url":null,"abstract":"<p><p>Employment of mesoporous silica nanostructures (MSNs) in the drug delivery field has shown a significant potential for improving the oral delivery of active pharmaceutical products with low solubility in water. Mirtazapine (MRT) is a tetracyclic antidepressant with poor water solubility (BCS Class II), which was recently approved as a potent drug used to treat severe depression. The principle of this research is to optimize the incorporation of Mirtazapine into MSNs to improve its aqueous solubility, loading efficiency, release performance, and subsequent bioavailability. The formulation was optimized by using of Box-Behnken Design, which allows simultaneous estimation of the impact of different types of silica (SBA-15, MCM-41, and Aluminate-MCM-41), a different drug to silica ratios (33.33%, 49.99%, and 66.66%), and different drug loading procedures (Incipient wetness, solvent evaporation, and solvent impregnation) on the MRT loading efficiency, aqueous solubility and dissolution rate. The optimized formula was achieved by loading MRT into SBA-15 at 33.33% drug ratio prepared by the incipient wetness method, which displayed a loading efficiency of 104.05%, water solubility of 0.2 mg/ml, and 100% dissolution rate after 30 min. The pharmacokinetic profile of the optimized formula was obtained by conducting the in<i>-vivo</i> study in rabbits which showed a marked improvement (2.14-fold) in oral bioavailability greater than plain MRT. The physicochemical parameters and morphology of the optimized formula were characterized by; gas adsorption manometry, scanning electron microscopy (SEM), polarized light microscopy (PLM), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD).</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"1582-1594"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10394867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced transdermal insulin basal release from silk fibroin (SF) hydrogels via iontophoresis.","authors":"Phimchanok Sakunpongpitiporn, Witthawat Naeowong, Anuvat Sirivat","doi":"10.1080/10717544.2022.2096717","DOIUrl":"10.1080/10717544.2022.2096717","url":null,"abstract":"<p><p>Insulin is the peptide hormone used to treat the diabetes patient. The hormone is normally taken by injection. The transdermal drug delivery system (TDDS) is an alternative route. The silk fibroin (SF) hydrogels were fabricated via solution casting as the insulin matrix. The release and release-permeation experiments of the insulin loaded SF hydrogels were carried out using a modified Franz-diffusion cell at 37 °C for 36 h, under the effects of SF concentrations, pH, and electric field. The release-permeation mechanism through the pig skin was from the Case-II transport with the constant release rate. The diffusion coefficient (D) increased with decreasing SF concentration due to a larger mesh size, and with increasing electric field due to the electroreplusive forces between the insulin and the SF hydrogels against the negatively-charged electrode, and the induced SF hydrogel expansion. The rate and amount of insulin release-permeation became relatively lower as it required a longer time to generate aqueous pathways through the pig skin. The present SF hydrogels are demonstrated here deliver insulin with the required constant release rate, and the suitable amount within a prescribed duration.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"2234-2244"},"PeriodicalIF":6.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/24/89/IDRD_29_2096717.PMC9848418.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9096334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pronounced capping effect of olaminosomes as nanostructured platforms in ocular candidiasis management.","authors":"Sadek Ahmed,&nbsp;Maha M Amin,&nbsp;Sarah Mohamed El-Korany,&nbsp;Sinar Sayed","doi":"10.1080/10717544.2022.2120926","DOIUrl":"https://doi.org/10.1080/10717544.2022.2120926","url":null,"abstract":"<p><p>The aim of this study was to formulate and boost ocular targeting of Fenticonazole Nitrate (FTN)-loaded olaminosomes in order to improve drug corneal permeation and candidiasis treatment. Olaminosomes were formulated by ethanol injection technique applying a central composite design. The independent variables were: span 80 amount (mg) (A), oleylamine concentration (mg%) (B) and oleic acid: drug ratio (C). The dependent responses were: percent entrapment efficiency (EE %), particle size (PS), poly-dispersity index (PDI), zeta potential (ZP) and <i>in vitro</i> drug release after 10 hours (Q10h). Numerical optimization by Design-Expert® software was adopted to select the optimum formula. This formula was chosen based on highest EE %, ZP (as absolute value) and Q10h and lowest PS and PDI. The optimum formula was subjected to further <i>in vitro</i> characterization via Differential scanning calorimetry, Transmission electron microscopy, Fourier transform infrared spectroscopy, pH determination, effect of storage, influence of terminal sterilization, detection of Minimal Inhibitory Concentration and <i>ex vivo</i> corneal penetration analysis. Safety and antifungal activity of the optimum formula were tested through various <i>in vivo</i> studies like ocular irritancy, corneal tolerance, corneal uptake and susceptibility test. The optimum formula with the maximum desirability value (0.972) revealed EE% (84.24%), PS (117.55 nm), ZP (-74.85 mV) and Q10h (91.26%) respectively. The optimum formula demonstrated ocular tolerance with enhanced corneal penetration behavior (428.66 µg/cm²) and boosted antifungal activity (56.13%) compared to FTN suspension (174.66 µg/cm² and 30.83%). The previous results ensured the ability of olaminosomes to enhance the corneal penetration and antifungal efficacy of Fenticonazole Nitrate.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"2945-2958"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9111534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in anti-multidrug resistance for nano-drug delivery system.","authors":"Changduo Wang, Fashun Li, Tianao Zhang, Min Yu, Yong Sun","doi":"10.1080/10717544.2022.2079771","DOIUrl":"10.1080/10717544.2022.2079771","url":null,"abstract":"<p><p>Chemotherapy for tumors occasionally results in drug resistance, which is the major reason for the treatment failure. Higher drug doses could improve the therapeutic effect, but higher toxicity limits the further treatment. For overcoming drug resistance, functional nano-drug delivery system (NDDS) has been explored to sensitize the anticancer drugs and decrease its side effects, which are applied in combating multidrug resistance (MDR) via a variety of mechanisms including bypassing drug efflux, controlling drug release, and disturbing metabolism. This review starts with a brief report on the major MDR causes. Furthermore, we searched the papers from NDDS and introduced the recent advances in sensitizing the chemotherapeutic drugs against MDR tumors. Finally, we concluded that the NDDS was based on several mechanisms, and we looked forward to the future in this field.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"1684-1697"},"PeriodicalIF":6.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9154776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43054633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifunctional icariin and tanshinone IIA co-delivery liposomes with potential application for Alzheimer's disease.","authors":"Jiao Wang,&nbsp;Liang Kong,&nbsp;Rui-Bo Guo,&nbsp;Si-Yu He,&nbsp;Xin-Ze Liu,&nbsp;Lu Zhang,&nbsp;Yang Liu,&nbsp;Yang Yu,&nbsp;Xue-Tao Li,&nbsp;Lan Cheng","doi":"10.1080/10717544.2022.2072543","DOIUrl":"https://doi.org/10.1080/10717544.2022.2072543","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) is a protective barrier for brain safety, but it is also a major obstacle to the delivery of drugs to the cerebral parenchyma such as the hippocampus, hindering the treatment of central nervous system diseases such as Alzheimer's disease (AD). In this work, an anti-AD brain-targeted nanodrug delivery system by co-loading icariin (ICA) and tanshinone IIA (TSIIA) into Aniopep-2-modified long-circulating (Ang2-ICA/TSIIA) liposomes was developed. Low-density lipoprotein receptor-related protein-1 (LRP1) was a receptor overexpressed on the BBB. Angiopep-2, a specific ligand of LRP1, exhibited a high binding efficiency with LRP1. Additionally, ICA and TSIIA, drugs with neuroprotective effects are loaded into the liposomes, so that the liposomes not only have an effective BBB penetration effect, but also have a potential anti-AD effect. The prepared Ang2-ICA/TSIIA liposomes appeared narrow dispersity and good stability with a diameter of 110 nm, and a round morphology. Cell uptake observations, BBB models <i>in vitro</i>, and imaging analysis <i>in vivo</i> showed that Ang2-ICA/TSIIA liposomes not only penetrate the BBB through endocytosis, but also accumulate in N2a cells or brain tissue. The pharmacodynamic analysis <i>in vivo</i> demonstrated that Ang2-ICA/TSIIA liposomes could improve AD-like pathological features in APP/PS1 mice, including inhibiting neuroinflammation and oxidative stress, reducing apoptosis, protecting neurons, and improving cognitive function. Therefore, Ang2-ICA/TSIIA liposomes are considered a potentially effective therapeutic strategy for AD.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"1648-1662"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/93/IDRD_29_2072543.PMC9154764.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10399111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microneedle mediated transdermal delivery of β-sitosterol loaded nanostructured lipid nanoparticles for androgenic alopecia.","authors":"Kousalya Prabahar,&nbsp;Ubaidulla Udhumansha,&nbsp;Nehal Elsherbiny,&nbsp;Mona Qushawy","doi":"10.1080/10717544.2022.2120927","DOIUrl":"https://doi.org/10.1080/10717544.2022.2120927","url":null,"abstract":"<p><p>Plant-derived 5 α-reductase inhibitors, such as β-sitosterol and phytosterol glycosides, have been used to treat androgenic alopecia, but their oral absolute bioavailability is poor. This study aimed to develop a transdermal drug delivery system of β-sitosterol (BS) using a nanostructured lipid carrier (NLC) incorporated into polymeric microneedles (MN). Using a high-speed homogenization method, NLC was formulated variables were optimized by Box-Behnken statistical design. The optimized formulation of BS-loaded NLCs was incorporated into the chitosan-based MNs to prepare NLC-loaded polymeric MNs (NLC-MNs) and evaluated using testosterone induced alopecia rats. The cumulative amount of β-sitosterol associated with NLC- MN which penetrated the rat skin in-vitro was 3612.27 ± 120.81 μg/cm², while from the NLC preparation was 2402.35 ± 162.5 μg/cm². The steady state flux (J_ss) of NLC-MN was significantly higher than that of the optimized NLC formulation (<i>P</i> < 0.05). Anagen/telogen ratio was significantly affected by NLC and NLC-MN, which was 2.22 ± 0.34, 1.24 ± 0.18 respectively compared to 0.26 ± 0.08 for animal group treated with testosterone. The reversal of androgen-induced hair loss in animals treated with β-sitosterol was a sign of hair follicle dominance in the anagenic growth phase. However, NLC-MN delivery system has shown significant enhancement of hair growth in rats. From these experimental data, it can be concluded that NLC incorporated MN transdermal system have potential in effective treatment of androgenic alopecia.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"3022-3034"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10003132/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9095149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and optimization of amphiphilic self-assembly into nanostructured liquid crystals for transdermal delivery of an antidiabetic SGLT2 inhibitor.","authors":"Nancy M Lotfy,&nbsp;Mohammed Abdallah Ahmed,&nbsp;Nada M El Hoffy,&nbsp;Ehab R Bendas,&nbsp;Nadia M Morsi","doi":"10.1080/10717544.2022.2144546","DOIUrl":"https://doi.org/10.1080/10717544.2022.2144546","url":null,"abstract":"<p><p>The anti-hyperglycemic sodium glucose co-transporter 2 inhibitor Canagliflozin (CFZ) represents a recent antihyperglycemic modality, yet it suffers from low oral bioavailability. The current work aims to formulate CFZ-loaded transdermal nanostructured liquid crystal gel matrix (NLCG) to improve its therapeutic efficiency. Pre-formulation study included the construction of pseudoternary phase diagrams to explore the effect of two conventional amphiphiles against amphiphilic tri-block copolymer in the formulation of NLCG. The influence of different co-solvents was also investigated with the use of monooleine as the oil. Physical characterization, morphological examination and skin permeation were performed for the optimized formulations. The formula of choice was further investigated for skin irritation and chemical stability. Pharmacodynamic evaluation of the successful formula was conducted on hyperglycemic as well as normoglycemic mice. In addition, oral glucose tolerance test was conducted. Results revealed the supremacy of Poloxamer for stabilizing and maximizing liquid crystal gel (LCG) area percentage that reached up to 12.6%. CFZ-NLCG2 isotropic formula showed the highest permeation parameters; maximum flux value of 7460 μg/cm² h and <i>Q</i>₂₄ of 5327 μg/cm². Pharmacodynamic evaluation revealed the superiority of the antihyperglycemic activity of CFZ-NLCG2 in fasting mice and its equivalence in the oral glucose tolerance test (OGTT) compared to the oral one. The obtained results confirmed the success of CFZ-NLCG2 in the transdermal delivery of CFZ in therapeutically effective concentration compared to the oral route, bypassing first pass effect; in addition, eliminates the possible gastrointestinal side effects related to the inhibition of intestinal sodium glucose co-transporter (SGLT) and maximizes its selectivity to the desired inhibition of renal SGLT.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"3340-3357"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9848419/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9097778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Docetaxel prodrug and hematoporphyrin co-assembled nanoparticles for anti-tumor combination of chemotherapy and photodynamic therapy.","authors":"Guolian Ren,&nbsp;Yujie Li,&nbsp;Canqi Ping,&nbsp;Danyu Duan,&nbsp;Ning Li,&nbsp;Jiaqi Tang,&nbsp;Rongrong Wang,&nbsp;Wenju Guo,&nbsp;Xiaomin Niu,&nbsp;Qiuyue Ji,&nbsp;Guoshun Zhang,&nbsp;Ruili Wang,&nbsp;Shuqiu Zhang","doi":"10.1080/10717544.2022.2147280","DOIUrl":"https://doi.org/10.1080/10717544.2022.2147280","url":null,"abstract":"<p><p>To realize the synergistic anti-tumor effect of chemotherapy and photodynamic therapy, the mono sulfide-modified docetaxel (DTX) prodrugs (DSD) provided by our laboratory and hematoporphyrin (HP) were used to physically prepare co-assembled nanoparticles (DSD/HP NPs) by nano-precipitation. For the first time, this study showed its characteristics, <i>in vitro</i> anti-tumor activity, pharmacokinetic behavior in rats, <i>in vivo</i> distribution, and pharmacodynamic effects on 4T1 tumor-bearing Bal b/c mice. DSD/HP NPs optimized by single-factor and response surface optimization had several distinct characteristics. First, it had dark purple appearance with particle size of 105.16 ± 1.24 nm, PDI of 0.168 ± 0.15, entrapment efficiency and drug loading of DSD and HP in DSD/HP NPs of 96.27 ± 1.03% and 97.70 ± 0.20%, 69.22 ± 1.03% and 20.03 ± 3.12%, respectively. Second, it had good stability and could release DTX and HP slowly in the media of pH 7.4 PBS with 10 mM DTT (H₂O₂). Moreover, DSD/HP NPs along with NiR treatment significantly inhibited 4T1 cells proliferation, and induced more reactive oxygen species and cells apoptosis. <i>In vivo</i> pharmacokinetic and pharmacodynamic studies showed that DSD/HP NPs could prolong the drug circulation time in rats, increase drug distribution in tumor site, obviously inhibit tumor growth, and decrease the exposure of drug to normal tissues. Therefore, DSD/HP NPs as a promising co-assembled nano-drug delivery system could potentially improve the therapeutic efficiency of chemotherapeutic drug and achieve better anti-tumor effects due to the combination of chemotherapy and photodynamic therapy.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"29 1","pages":"3358-3369"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cb/79/IDRD_29_2147280.PMC9848415.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9097781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}