POxylated Dendrimer‐Based Nano‐in‐Micro Dry Powder Formulations for Inhalation Chemotherapy

Restani, Rita B.; Pires, Rita F.; Tolmatcheva, Anna; Cabral, Rita; Baptista, Pedro V.; Fernandes, Alexandra R.; Casimiro, Teresa; Bonifácio, Vasco D. B.; Aguiar‐Ricardo, Ana

doi:10.1002/open.201800093

Cited by 15 publications

(4 citation statements)

References 29 publications

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“…The power law model has been reported for paclitaxel and doxorubicin OIDPs [ 91 ]. In this research work, the dissolution of nano-in-micro formulations for DPI was investigated by suspending the formulation particles in 10 mL of buffer solution.…”

Section: Application Of Statistics To Dissolution Datamentioning

confidence: 99%

In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances

2023

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In vitro dissolution and permeability testing aid the simulation of the in vivo behavior of inhalation drug products. Although the regulatory bodies have specific guidelines for the dissolution of orally administered dosage forms (e.g., tablets and capsules), this is not the case for orally inhaled formulations, as there is no commonly accepted test for assessing their dissolution pattern. Up until a few years ago, there was no consensus that assessing the dissolution of orally inhaled drugs is a key factor in the assessment of orally inhaled products. With the advancement of research in the field of dissolution methods for orally inhaled products and a focus on systemic delivery of new, poorly water-soluble drugs at higher therapeutic doses, an evaluation of dissolution kinetics is proving crucial. Dissolution and permeability testing can determine the differences between the developed formulations and the innovator’s formulations and serve as a useful tool in correlating in vitro and in vivo studies. The current review highlights recent advances in the dissolution and permeability testing of inhalation products and their limitations, including recent cell-based technology. Although a few new dissolution and permeability testing methods have been established that have varying degrees of complexity, none have emerged as the standard method of choice. The review discusses the challenges of establishing methods that can closely simulate the in vivo absorption of drugs. It provides practical insights into method development for various dissolution testing scenarios and challenges with dose collection and particle deposition from inhalation devices for dissolution tests. Furthermore, dissolution kinetic models and statistical tests to compare the dissolution profiles of test and reference products are discussed.

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Section: Application Of Statistics To Dissolution Datamentioning

confidence: 99%

In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances

2023

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“…Free PTX had a IC 50 of 0.094 µM after 48 h of incubation against the hepatocellular carcinoma cell line HepG2, a value that was dramatically reduced to 1.23 nM and 1.90 nM after encapsulation into PURE G4 -OEtOx 48 and PURE G4 -OMeOx 48 , respectively [ 84 ]. The encapsulation of other anticancer agents into PURE dendrimers was also successfully achieved, as in the case of the nano-in-microparticles developed for inhalation chemotherapy [ 85 ].…”

Section: Dendrimers General Role In Cancermentioning

confidence: 99%

A Glimpse into Dendrimers Integration in Cancer Imaging and Theranostics

Cruz

Barbosa

Antunes

et al. 2023

IJMS

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Cancer is a result of abnormal cell proliferation. This pathology is a serious health problem since it is a leading cause of death worldwide. Current anti-cancer therapies rely on surgery, radiation, and chemotherapy. However, these treatments still present major associated problems, namely the absence of specificity. Thus, it is urgent to develop novel therapeutic strategies. Nanoparticles, particularly dendrimers, have been paving their way to the front line of cancer treatment, mostly for drug and gene delivery, diagnosis, and disease monitoring. This is mainly derived from their high versatility, which results from their ability to undergo distinct surface functionalization, leading to improved performance. In recent years, the anticancer and antimetastatic capacities of dendrimers have been discovered, opening new frontiers to dendrimer-based chemotherapeutics. In the present review, we summarize the intrinsic anticancer activity of different dendrimers as well as their use as nanocarriers in cancer diagnostics and treatment.

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“…In this sense, dendrimers are an outstanding drug delivery platform, and many efforts have been made in the last few years to circumvent their cytotoxicity [21], encouraging the fast translation into clinic applications in a near future. In this study, we developed polyurea (PURE) dendrimers, which are a special case of non-toxic [22] and non-hemolytic dendrimers up to very high concentrations (circa 50 µM, unpublished data), and that have already been explored in different nanotherapeutic strategies [23][24][25][26]. The use of folate-targeted dendrimers is an emergent approach in cancer-targeted chemotherapy [27].…”

Section: Introductionmentioning

confidence: 99%

Polyurea Dendrimer Folate-Targeted Nanodelivery of l-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance

et al. 2020

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Ovarian cancer is a highly lethal disease, mainly due to chemoresistance. Our previous studies on metabolic remodeling in ovarian cancer have supported that the reliance on glutathione (GSH) bioavailability is a main adaptive metabolic mechanism, also accounting for chemoresistance to conventional therapy based on platinum salts. In this study, we tested the effects of the in vitro inhibition of GSH synthesis on the restoration of ovarian cancer cells sensitivity to carboplatin. GSH synthesis was inhibited by exposing cells to l-buthionine sulfoximine (l-BSO), an inhibitor of γ-glutamylcysteine ligase (GCL). Given the systemic toxicity of l-BSO, we developed a new formulation using polyurea (PURE) dendrimers nanoparticles (l-BSO@PUREG4-FA2), targeting l-BSO delivery in a folate functionalized nanoparticle.

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POxylated Dendrimer‐Based Nano‐in‐Micro Dry Powder Formulations for Inhalation Chemotherapy

Cited by 15 publications

References 29 publications

In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances

In Vitro Dissolution and Permeability Testing of Inhalation Products: Challenges and Advances

A Glimpse into Dendrimers Integration in Cancer Imaging and Theranostics

Polyurea Dendrimer Folate-Targeted Nanodelivery of l-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance

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