Recent progress in drying technologies for improving the stability and delivery efficiency of biopharmaceuticals

Emami Fakhrossadat,Keihan Shokooh Mahsa,Mostafavi Yazdi Seyed Jamaleddin 한국약제학회 2023 Journal of Pharmaceutical Investigation Vol.53 No.1

Background Most biopharmaceuticals are developed in liquid dosage forms that are less stable than solid forms. To ensure the stability of biopharmaceuticals, it is critical to use an effective drying technique in the presence of an appropriate stabilizing excipient. Various drying techniques are available for this purpose, such as freeze drying or lyophilization, spray drying, spray freeze-drying, supercritical fluid drying, particle replication in nonwetting templates, and fluidized bed drying. Area covered In this review, we discuss drying technologies and their applications in the production of stable solid-state biopharmaceuticals, providing examples of commercially available products or clinical trial formulations. Alongside this, we also review how different analytical methods may be utilized in the evaluation of aerosol performance and powder characteristics of dried protein powders. Finally, we assess the protein integrity in terms of conformational and physicochemical stability and biological activity. Expert opinion With the aim of treating either infectious respiratory diseases or systemic disorders, inhaled biopharmaceuticals reduce both therapeutic dose and cost of therapy. Drying methods in the presence of optimized protein/stabilizer combinations, produce solid dosage forms of proteins with greater stability. A suitable drying method was chosen, and the process parameters were optimized based on the route of protein administration. With the ongoing trend of addressing deficiencies in biopharmaceutical production, developing new methods to replace conventional drying methods, and investigating novel excipients for more efficient stabilizing effects, these products have the potential to dominate the pharmaceutical industry in the future.

Cetuximab-anchored gold nanorod mediated photothermal ablation of breast cancer cell in spheroid model embedded with tumor associated macrophage

Fakhrossadat Emami,Asmita Banstola,Jee-Heon Jeong,Yook, Simmyung 한국공업화학회 2022 Journal of Industrial and Engineering Chemistry Vol.106 No.-

Triple-negative breast cancer constitutes 15 – 20% of all breast cancer and is considered one of the mostaggressive forms of breast cancer. Clinical studies have suggested that the high numbers of infiltratingtumor-associated macrophage (TAM) act as a critical contributor behind the aggression of TNBC. Therefore, this study was focused on the preparation of a TNBC spheroid model with M2-like macrophages(M2-M) since it closely simulated the tumor microenvironment observed in clinical TNBC tumors. High EGFR expression in TNBC highlights the importance of cetuximab (Cmab)-assisted cellular internalizationinto the EGFR overexpressing TNBC cell line. The Cmab-anchored gold nanorod (GNR)-mediatedphotothermal approach was successfully developed to treat the TAM-infiltrated TNBC spheroid model. MDA-MB-231 spheroids with a diameter of 260 ± 10 lm were successfully prepared. An increase inthe IC50 of doxorubicin in MDA-MB-231 spheroids with M2-M compared to the without M2-M group suggestedthat TAM-mediated development of resistance. The in vitro cytotoxicity assay demonstrated thatthere was elevated apoptosis expression (PARP and caspase-9), cell cycle arrest (G2/M phase), and cytotoxiceffects following treatment with Cmab-GNR plus NIR irradiation. Moreover, there was no significantdifference between the cytotoxic effect of Cmab-GNR plus NIR with M2-M and without M2-M group. Thus, our study highlighted that Cmab-GNR with NIR were able to overcome TAM-acquired resistancein the tumor model, which might be due to the polarization of the protumoral phenotype to the antitumoralphenotype.

Polymeric and lipid-based drug delivery systems for treatment of glioblastoma multiforme

Ramesh Duwa,Fakhrossadat Emami,이수연,정지헌,육심명 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.79 No.-

Glioblastoma multiforme (GBM) is the most aggressive, malignant brain tumor found in adults, and has ashort median survival time (MST). GBM is a heterogeneous group of brain tumors, is highly prone todevelop resistance and likely to recur. In the context of GBM, the delivery of anti-cancer drugs ischallenging because the blood brain barrier (BBB) restricts the passage of small molecules. Currently,nanomedicines based on liposomes, micelles, polymeric nanoparticles, and microparticles have attractedmuch attention, because they can cross the BBB and deliver anti-cancer drugs specifically to brain tumors. In this context, hydrogel-based systems incorporating nanoparticles, implantable carmustine wafers,microspheres, and lipid-based nanoparticles now appear to offer more effective, safer treatmentstrategies than conventional chemotherapeutic regimens. This review describes different polymerichydrogel, chitosan, dendrimers, wafers, microspheres, and lipid-based nanoparticles like liposomes andsolid-lipid nanoparticles that offers prominent strategies for the treatment and diagnosis of GBM.

Current Applications of Gold Nanoparticles for Medical Imaging and as Treatment Agents for Managing Pancreatic Cancer

Asmita Banstola,Fakhrossadat Emami,정지헌,육심명 한국고분자학회 2018 Macromolecular Research Vol.26 No.11

Pancreatic cancer is an extremely heterogeneous, malignant disease with a complicated tumor microenvironment and a dismal prognosis. Extensive stroma surrounding the cancer and the sequestering of chemotherapeutic agents play dominant roles in tumor growth and metastasis and in suppressing the delivery of cytotoxic drugs to tumor cells. Currently, nanoscience is in the forefront of developments aimed at devising novel techniques to treat tumors. Gold nanoparticles (GNPs) are often used as potential imaging and therapeutic agents for cancers, since they offer: (1) Passive targeting because of better permeation and retention effects, (2) photothermal effects caused by efficient light-to-heat conversion, and (3) the potential to use simple gold-thiol bioconjugation chemistry to conjugate desired molecules for targeted drug delivery. Together, these benefits can increase the therapeutic success of GNPs when used in combination with conventional treatment strategies, such as surgery, chemotherapy, or radiotherapy. In this review, we discuss current trends in GNP research in the field of pancreatic cancer theranostics.

Polymeric and lipid-based drug delivery systems for treatment of glioblastoma multiforme

Duwa, Ramesh,Emami, Fakhrossadat,Lee, Sooyeun,Jeong, Jee-Heon,Yook, Simmyung Elsevier 2019 Journal of industrial and engineering chemistry Vol.79 No.-

<P><B>Abstract</B></P> <P>Glioblastoma multiforme (GBM) is the most aggressive, malignant brain tumor found in adults, and has a short median survival time (MST). GBM is a heterogeneous group of brain tumors, is highly prone to develop resistance and likely to recur. In the context of GBM, the delivery of anti-cancer drugs is challenging because the blood brain barrier (BBB) restricts the passage of small molecules. Currently, nanomedicines based on liposomes, micelles, polymeric nanoparticles, and microparticles have attracted much attention, because they can cross the BBB and deliver anti-cancer drugs specifically to brain tumors. In this context, hydrogel-based systems incorporating nanoparticles, implantable carmustine wafers, microspheres, and lipid-based nanoparticles now appear to offer more effective, safer treatment strategies than conventional chemotherapeutic regimens. This review describes different polymeric hydrogel, chitosan, dendrimers, wafers, microspheres, and lipid-based nanoparticles like liposomes and solid-lipid nanoparticles that offers prominent strategies for the treatment and diagnosis of GBM.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Poly(lactic acid)/poly(lactic‑co‑glycolic acid) particulate carriers for pulmonary drug delivery

Dong Hee Na,Fakhrossadat Emami,Seyed Jamaleddin Mostafavi Yazdi 한국약제학회 2019 Journal of Pharmaceutical Investigation Vol.49 No.4

Background Pulmonary route is an attractive target for both systemic and local drug delivery, with the advantages of a large surface area, rich blood supply, and absence of first-pass metabolism. Numerous polymeric micro/nanoparticles have been designed and studied for controlled and targeted drug delivery to the lung. Area covered Among the natural and synthetic polymers for polymeric particles, poly(lactic acid) (PLA) and poly(lacticco- glycolic acid) (PLGA) have been widely used for the delivery of anti-cancer agents, anti-inflammatory drugs, vaccines, peptides, and proteins because of their highly biocompatible and biodegradable properties. This review focuses on the characteristics of PLA/PLGA particles as carriers of drugs for efficient delivery to the lung. Furthermore, the manufacturing techniques of the polymeric particles, and their applications for inhalation therapy were discussed. Expert opinion Compared to other carriers including liposomes, PLA/PLGA particles present a high structural integrity providing enhanced stability, higher drug loading, and prolonged drug release. Adequately designed and engineered polymeric particles can contribute to a desirable pulmonary drug delivery characterized by a sustained drug release, prolonged drug action, reduction in the therapeutic dose, and improved patient compliance.