Vol 25, No 6 (2024)

Biotechnology

The Natural Product Oridonin as an Anticancer Agent: Current Achievements and Problems

Ye S., Jiang J., Hu X., Huang S.

Abstract

Oridonin, an active diterpenoid isolated from traditional Chinese herbal medicine, has received a rising attention for its remarkable roles in cancer therapy. In recent years, increasing evidences have revealed that oridonin inhibits the occurrence and development of tumor cells through multiple mechanisms, including induction of apoptosis and autophagy, cell cycle arrest, and inhibition of angiogenesis as well as migration and invasion. In addition, several molecular signal targets have been identified, including ROS, EGFR, NF-κB, PI3K/Akt, and MAPK. In this paper, we review considerable knowledge about the molecular mechanisms and signal targets of oridonin, which has been studied in recent years. It is expected that oridonin may be developed as a novel anti-tumor herbal medicine in human cancer treatment.

Current Pharmaceutical Biotechnology. 2024;25(6):655-664
pages 655-664 views

Effect of Host Cell Protein on Chinese Hamster Ovary Recombinant Protein Production and its Removal Strategies: A Mini Review

Zhao Y., Li H., Fan Z., Wang T.

Abstract

Chinese hamster ovary cells are the main expression system for recombinant therapeutic proteins. During the production of these proteins, certain host cell proteins are secreted, broken down, and released by host cells in the culture along with the proteins of interest. These host cell proteins are often difficult to remove during the downstream purification process, and thus affect the quality, safety, and effectiveness of recombinant protein biopharmaceutical products and increase the production cost of recombinant therapeutic proteins. Therefore, host cell protein production must be reduced as much as possible during the production process and eliminated during purification. This article reviews the harm caused by host cell proteins in the production of recombinant protein drugs using Chinese hamster ovary cell, factors affecting host cell proteins, the monitoring and identification of these proteins, and methods to reduce their type and quantity in the final product.

Current Pharmaceutical Biotechnology. 2024;25(6):665-675
pages 665-675 views

Use of Albumin for Drug Delivery as a Diagnostic and Therapeutic Tool

Karami E., Mesbahi Moghaddam M., Kazemi-Lomedasht F.

Abstract

Drug delivery is an important topic that has attracted the attention of researchers in recent years. Albumin nanoparticles play a significant role in drug delivery as a carrier due to their unique characteristics. Albumin is non-toxic, biocompatible, and biodegradable. Its structure is such that it can interact with different drugs, which makes the treatment of the disease faster and also reduces the side effects of the drug. Albumin nanoparticles can be used in the diagnosis and treatment of many diseases, including cancer, diabetes, Alzheimer's, etc. These nanoparticles can connect to some compounds, such as metal nanoparticles, antibodies, folate, etc. and create a powerful nanostructure for drug delivery. In this paper, we aim to investigate albumin nanoparticles in carrier format for drug delivery application. In the beginning, different types of albumin and their preparation methods were discussed, and then albumin nanoparticles were discussed in detail in diagnosing and treating various diseases.

Current Pharmaceutical Biotechnology. 2024;25(6):676-693
pages 676-693 views

Natural Polyphenols in Cancer Management: Promising Role, Mechanisms, and Chemistry

Upadhyay P., Singh S., Vishwakarma V.

Abstract

Background:Although cancers emerge rapidly and cancer cells divide aggressively, which affects our vital organ systems. Recently, cancer treatments are targeted immune systems mediating intrinsic cellular mechanisms. Natural efficacious polyphenols have been exhibited to help prevent most cancers and reverse the progression of cancers.

Methods:Many resources have been used to know the promising role of polyphenols in preventing and treating cancers. The electronic databases include Science Direct, Google, Google Scholar, PubMed, and Scopus. The search was limited to the English language only.

Results:Polyphenols have been reported as anti-metastatic agents that explore the promising role of these compounds in cancer prevention. Such agents act through many signaling pathways, including PI3K/Akt and TNF-induced signaling pathways. The chemical modifications of polyphenols and the structure-activity relationships (SARs) between polyphenols and anticancer activities have also been discussed.

Conclusion:Many research papers were reported to explain the anti-cancer potential of Polyphenols, The SARs between polyphenols and anti-cancer activities, which correlate structures of polyphenols with significant chemotherapeutic action. The mechanism of anti-cancer potential is to be added for searching for new anti-cancer natural products.

Current Pharmaceutical Biotechnology. 2024;25(6):694-712
pages 694-712 views

Nanostructured Lipid Carriers Mediated Drug Delivery to Posterior Segment of Eye and their In-vivo Successes

Singh A., Kumar M., Upadhyay P.

Abstract

Background:The disease of the posterior segment of the eye is a major concern worldwide, and it affects more than 300 million people and leads to serious visual deterioration. The current treatment available is invasive and leads to serious eye complications. These shortcomings and patient discomfort lead to poor patient compliance. In the last decade, Nanostructured lipid carriers (NLC) have established a remarkable milestone in the delivery of drug substances to the posterior segment of the eye. Additionally, NLC can reduce the clearance due to adhesive properties which are imparted due to nano-metric size. This attribute might reduce the adverse effects associated with intravitreal therapy and thus enhance therapeutic efficacy, eventually raising patient adherence to therapy. The current review provides an inclusive account of NLC as a carrier to target diseases of the posterior segment of the eye.

Objective:The review focuses on the various barrier encountered in the delivery of drugs to the posterior segment of the eye and the detail about the physicochemical property of drug substances that are considered to be suitable candidates for encapsulation to lipid carriers. Therefore, a plethora of literature has been included in this review. The review is an attempt to describe methods adopted for assessing the in-vivo behavior that strengthens the potential of NLC to treat the disease of the posterior segment of the eye.

Conclusion:These NLC-based systems have proven to be a promising alternative in place of invasive intravitreal injections with improved patient compliance.

Current Pharmaceutical Biotechnology. 2024;25(6):713-723
pages 713-723 views

How do Mutations of Mycobacterium Genes Cause Drug Resistance in Tuberculosis?

Hou K., Jabeen R., Sun L., Wei J.

Abstract

A steady increase in the prevalence of drug-resistant tuberculosis (DR-TB) has already been reported in Pakistan. In addition, DR-TB is gradually changing from one-drug resistance to multi-drug resistance, which is a serious challenge for tuberculosis treatment. This review provides an overview of the anti-tuberculosis drugs and focuses on the molecular mechanisms of drug resistance in Mycobacterium tuberculosis, with the hope that it will contribute to the study of drug resistance in response to the emergence of multidrug-resistant tuberculosis.

Current Pharmaceutical Biotechnology. 2024;25(6):724-736
pages 724-736 views

Comprehensive Review on Phytoconstituents-based Nanomedicine for the Treatment of Atopic Dermatitis

Varshney M., Bahadur S.

Abstract

Atopic dermatitis (AD) is known as a chronic disease characterized by eczematous and pruritus skin lesions. The pathology behind atopic dermatitis etiology is loss of epidermal barrier, which prevents the production of protein filaggrin that can induce T-cell infiltration and inflammation. Treatment of AD is majorly based on limiting skin repair as well as reducing inflammation and itching. There are several remedies available for the treatment of AD, such as Janus kinase and calcineurin inhibitors, topical corticosteroids, and phosphodiesterase-4 inhibitors. The conventional formulations in the market have limited safety and efficacy. Hence, effective treatment of atopic dermatitis requires the development of novel, efficacious, reliable, and specific therapies. Recent research data have revealed that some naturally occurring medicinal plants have potential applications in the management of AD through different mechanisms. The nanotechnology-based therapeutics have gained a lot of attention in the last decade for the improvement in the activity of drugs having low absorption due to poor solubility, thus leading to lesser bioavailability. Therapies based on nanotechnology can be an effective way to overcome these obstacles. Due to their effective propensity to provide better drug diffusion and bioavailability as well as drug targeting potential at the desired site of action, these approaches may have decreased adverse drug effects, better penetration, and enhanced therapeutic efficacy. Hence, this review highlights the potential of phytoconstituents-based novel formulations for the treatment of atopic dermatitis. Furthermore, recent patents on therapeutic approaches to atopic dermatitis have also been briefly described.

Current Pharmaceutical Biotechnology. 2024;25(6):737-756
pages 737-756 views

Cubosomes: An Emerging and Promising Drug Delivery System for Enhancing Cancer Therapy

Singh S., Sachan K., Verma S., Singh N., Singh P.

Abstract

Cancer and other diseases can be treated with cubosomes, which are lyotropic nonlamellar liquid crystalline nanoparticles (LCNs). These cubosomes can potentially be a highly versatile carrier with theranostic efficacy, as they can be ingested, applied topically, or injected intravenously. Recent years have seen substantial progress in the synthesis, characterization, regulation of drug release patterns, and target selectivity of loaded anticancer bioactive compounds. However, its use in clinical settings has been slow and necessitates additional proof. Recent progress and roadblocks in using cubosomes as a nanotechnological intervention against various cancers are highlighted. In the last few decades, advances in biomedical nanotechnology have allowed for the development of \"smart\" drug delivery devices that can adapt to external stimuli. By improving therapeutic targeting efficacy and lowering the negative effects of payloads, these well-defined nanoplatforms can potentially promote patient compliance in response to specific stimuli. Liposomes and niosomes, two other well-known vesicular systems, share a lipid basis with cubosomes. Possible applications include a novel medication delivery system for hydrophilic, lipophilic, and amphiphilic drugs. We evaluate the literature on cubosomes, emphasizing their potential use in tumor-targeted drug delivery applications and critiquing existing explanations for cubosome self-assembly, composition, and production. As cubosome dispersion has bioadhesive and compatible features, numerous drug delivery applications, including oral, ocular, and transdermal, are also discussed in this review.

Current Pharmaceutical Biotechnology. 2024;25(6):757-771
pages 757-771 views

BAO-Ag-NPs as Promising Suppressor of ET-1/ICAM-1/VCAM-1 Signaling Pathway in ISO-induced AMI in Rats

Mosaad Y., Ateyya H., Hussein M., Moro A., Abdel-Wahab E., El-Ella A., Nassar Z.

Abstract

Objectives:Acute myocardial infarction (AMI) is the most prevalent cause of myocardial fibrosis and the leading cause of mortality from cardiovascular disease. The goal of this work was to synthesize Balanites aegyptiaca oil-silver nanoparticles (BAO-Ag-NPs) and evaluate their cardioprotective effect against ISO-induced myocardial infarction in rats, as well as their mechanism.

Materials and Methods:BAO was isolated, and the unsaturated fatty acids were estimated. BAO-Ag-NPs was prepared, LD50 was calculated to evaluate its cardioprotective activity against ISO (85 mg/kg)-induced AMI. Different doses of BAO-Ag-NPs (1/50 LD50; 46.6 mg/kg.b.w and 1/20 LD50; 116.5 mg) were received to the rats.

Results:The total fatty acids and unsaturated fatty acids generated by BAO were 909.63 and 653.47 mg/100 g oil, respectively. Oleic acid methyl ester, 9-octadecenoic acid methyl ester, and 9, 12-Octadecadienoic acid methyl ester were the predominant ingredients, with concentrations of 107.6, 243.42, and 256.77 mg/100 g oil, respectively. According to TEM and DLS examinations, BAO-Ag-NPs have a size of 38.20 ± 2.5 nm and a negative zeta potential of -19.82 ± 0.30 mV, respectively. The LD50 of synthesized BAO-Ag-NPs is 2330 mg. On the other hand, BAOAg- NPs reduce myocardial necrosis by lowering increased BNP, cTnI, CK-MB, TC, TG, MDA, MMP2, TGF-β1, PGE2, and IL-6 levels. Furthermore, BAO-Ag-NPs inhibit the expression of ET-1, ICAM-1, and VCAM-1 genes as well as enhance HDL-C, CAT, and GSH levels when compared to the ISO-treated group of rats. Histopathological findings suggested that BAO-Ag- NPs enhance cardiac function by increasing posterior wall thickness in heart tissues.

Conclusion:BAO-Ag-NPs protect against AMI in vivo by regulating inflammation, excessive autophagy, and oxidative stress, as well as lowering apoptosis via suppression of the ET-1, ICAM-1, and VCAM-1 signaling pathways.

Current Pharmaceutical Biotechnology. 2024;25(6):772-786
pages 772-786 views

Delivery of Agarose-aided Sprays to the Posterior Nose for Mucosa Immunization and Short-term Protection against Infectious Respiratory Diseases

Seifelnasr A., Talaat M., Si X., Xi J.

Abstract

Aim:The study aimed to deliver sprays to the posterior nose for mucosa immunization or short-term protection.

Background:Respiratory infectious diseases often enter the human body through the nose. Sars- Cov-2 virus preferentially binds to the ACE2-rich tissue cells in the Nasopharynx (NP). Delivering medications to the nose, especially to the NP region, provides either a short-term protective/ therapeutic layer or long-term mucosa immunization. Hydrogel-aided medications can assist film formation, prolong film life, and control drug release. However, conventional nasal sprays have failed to dispense mediations to the posterior nose, with most sprays lost in the nasal valve and front turbinate.

Objective:The objective of the study was to develop a practical delivery system targeting the posterior nose and quantify the dosimetry distribution of agarose-saline solutions in the nasal cavity.

Methods:The solution viscosities with various hydrogel concentrations (0.1-1%) were measured at different temperatures. Dripping tests on a vertical plate were conducted to understand the hydrogel concentration effects on the liquid film stability and mobility. Transparent nasal airway models were used to visualize the nasal spray deposition and liquid film translocation.

Result:Spray dosimetry with different hydrogel concentrations and inhalation flow rates was quantified on a total and regional basis. The solution viscosity increased with decreasing temperature, particularly in the range of 60-40oC. The liquid viscosity, nasal spray atomization, and liquid film mobility were highly sensitive to the hydrogel concentration. Liquid film translocations significantly enhanced delivered doses to the caudal turbinate and nasopharynx when the sprays were administered at 60oC under an inhalation flow rate of 11 L/min with hydrogel concentrations no more than 0.5%. On the other hand, sprays with 1% hydrogel or administered at 40oC would significantly compromise the delivered doses to the posterior nose.

Conclusion:Delivering sufficient doses of hydrogel sprays to the posterior nose is feasible by leveraging the post-administration liquid film translocation.

Current Pharmaceutical Biotechnology. 2024;25(6):787-798
pages 787-798 views