Solid dosage forms of biopharmaceuticals such as therapeutic proteins could provide enhanced bioavailability, improved storage stability, as well as expanded alternatives to parenteral administration. Although numerous drying methods have been used for preparing dried protein powders, choosing a suitable drying technique remains a challenge. In this review, the most frequent drying methods, such as freeze drying, spray drying, spray freeze drying, and supercritical fluid drying, for improving the stability and bioavailability of therapeutic proteins, are discussed. These technologies can prepare protein formulations for different applications as they produce particles with different sizes and morphologies. Proper drying methods are chosen, and the critical process parameters are optimized based on the proposed route of drug administration and the required pharmacokinetics. In an optimized drying procedure, the screening of formulations according to their protein properties is performed to prepare a stable protein formulation for various delivery systems, including pulmonary, nasal, and sustained-release applications.

Colorectal cancer (CRC) is the third leading cause of cancer-related death worldwide. The prognosis and overall survival of CRC are known to be significantly correlated with the overexpression of PD-L1. Since combination therapies can significantly improve therapeutic efficacy, we constructed doxorubicin (DOX) conjugated and anti-PD-L1 targeting gold nanoparticles (PD-L1-AuNP-DOX) for the targeted chemo-photothermal therapy of CRC. DOX and anti-PD-L1 antibody were conjugated to the α-terminal end group of lipoic acid polyethylene glycol N-hydroxysuccinimide (LA-PEG-NHS) using an amide linkage, and PD-L1-AuNP-DOX was constructed by linking LA-PEG-DOX, LA-PEG-PD-L1, and a short PEG chain on the surface of AuNP using thiol-Au covalent bonds. Physicochemical characterizations and biological studies of PD-L1-AuNP-DOX were performed in the presence of near-infrared (NIR) irradiation (biologic studies were conducted using cellular uptake, apoptosis, and cell cycle assays in CT-26 cells). PD-L1-AuNP-DOX (40.0 ± 3.1 nm) was successfully constructed and facilitated the efficient intracellular uptake of DOX as evidenced by pronounced apoptotic effects (66.0%) in CT-26 cells. PD-L1-AuNP-DOX treatment plus NIR irradiation significantly and synergistically suppressed the in vitro proliferation of CT-26 cells by increasing apoptosis and cell cycle arrest. The study demonstrates that PD-L1-AuNP-DOX in combination with synergistic targeted chemo-photothermal therapy has a considerable potential for the treatment of localized CRC.

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.

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Triple negative breast cancer (TNBC) with poor prognosis and aggressive nature accounts for 10–20% of all invasive breast cancer (BC) cases and is detected in as much as 15% of individuals diagnosed with BC. Currently, due to the absence of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) receptor, there is no hormone-based therapy for TNBC. In addition, there are still no FDA-approved targeted therapies for patients with TNBC. TNBC treatment is challenging owing to poor prognosis, tumor heterogeneity, chemotherapeutic side effects, the chance of metastasis, and multiple drug-resistance. Therefore, various bio-inspired tumor-homing nano systems responding to intra- and extra- cellular stimuli are an urgent need to treat TNBC patients who do not respond to current chemotherapy. In this review, intensive efforts have been made for exploring cell-membrane coated nanoparticles and immune cell-targeted nanoparticles (immunotherapy) to modulate the tumor microenvironment and deliver accurate amounts of therapeutic agents to TNBC without stimulating the immune system.

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