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Nanostructured Lipid Carriers for the Delivery of Natural Bioactive Compounds

Shamsuddin NAM, Zulfakar MH

Curr Drug Deliv, 2023;20(2):127-143.
PMID: 35331113 DOI: 10.2174/1567201819666220324094234

Natural products contain bioactive compounds that are produced naturally via synthetic or semisynthetic processes. These bioactive compounds play significant biological roles, especially for growth as well as in defense mechanisms against pathogens. Bioactive compounds in natural products have been extensively studied in recent decades for their pharmacological activities, such as anticancer, wound healing, anti-microbial, anti-inflammatory, and anti-oxidative properties. However, their pharmaceutical significance has always been hindered by their low bioavailability and instability with variations in pH, temperature, and exposure to light. Nanotechnology paves the way for the development of drug delivery systems by enhancing therapeutic efficacy. Nanostructured lipid carriers, a lipidbased drug delivery system, are recently being studied to improve the biocompatibility, biodegradability, bioavailability, solubility, permeability, and shelf life of bioactive compounds in the pharmaceutical industry. The ideal component and preparation method for bioactive compounds in nanostructured lipid carrier development is necessary for their physicochemical properties and therapeutic efficiency. Therefore, this review seeks to highlight recent developments, preparation, and application of nanostructured lipid carriers as carriers for natural bioactive compounds in improving their therapeutic potential in drug delivery systems.
Promises of Molecular Pharmaceutics in the Development of Novel Drug Delivery Formulations

Kumar P, Chaudhary B, Jain V, Baboota S, Shivanandy P, Alharbi KS, et al.

Curr Drug Deliv, 2023;20(9):1262-1274.
PMID: 36380413 DOI: 10.2174/1567201820666221114113637

Molecular pharmaceutics play a critical role in the drug delivery system, representing the direct interconnection of drug bioavailability with its molecular form. There is a diversity in the molecular structures by which it affects its properties, such as amorphous form, crystalline form, partialamorphous molecular dispersion, and disordered state. The active pharmaceutical ingredient (API) and the excipients utilized in the formulation process contain various divergent modes used in the formulation process. They include better formulations of any type to obtain good quality pharmaceutical products. This review reveals how the molecular states affect the API and are important in maintaining the quality of dosage forms. Furthermore, the physio-chemical properties of the components and various pharmaceutical approaches employed in the formulation of dosage forms are studied from the point of view of molecular pharmaceutics.
Circumventing the Gastrointestinal Barrier for Oral Delivery of Therapeutic Proteins and Peptides (PPTS): Current Trends and Future Trajectories

Hashim LE, Sabri AH, Mohamad MA, Anjani QK, Mustaffa MF, Abdul Hamid K

Curr Drug Deliv, 2024;21(2):211-235.
PMID: 37076462 DOI: 10.2174/1567201820666230418091506

Therapeutic proteins and peptides (PPTs) have become one of the most important biological molecules for the management of many common and complex diseases due to their high specificity and high bioactivity. However, these biomolecules are mainly given by the hypodermic injection, which often leads to poor patient compliance due to the invasive nature of this route of administration. The oral route has been considered the most convenient and patient-friendly route for drug delivery relative to hypodermic injections. Despite the ease and simplicity conferred by oral administration, this drug delivery route suffers rapid peptide degradation in gastric fluid and low intestinal uptake. In order to circumvent these issues, several strategies, such as enzyme inhibitors, permeation enhancers, chemical modification, mucoadhesive and stimuli-responsive polymers, and specialised particulate formulation have been developed. Such strategies are designed with the aim of protecting PPTs from the harsh gastrointestinal environment as well as providing a strategy to enhance the uptake of the therapeutic across the gastrointestinal tract. This review aims to provide an overview of the current development in enteral drug delivery strategies for PPTs. The design of these drug delivery systems in overcoming physical and chemical barriers along the gastrointestinal tract while improving oral bioavailability will be highlighted and discussed.
Lopinavir-Loaded Self-Nanoemulsifying Drug Delivery System for Enhanced Solubility: Development, Characterisation and Caco-2 Cell Uptake

Khan AA, Akhtar S, Yadav Y, Atiya A, Alelwani W, Bannunah AM, et al.

Curr Drug Deliv, 2023;20(10):1474-1486.
PMID: 35980056 DOI: 10.2174/1567201819666220817111054

BACKGROUND: The antiretroviral protease inhibitor drug, lopinavir (LPV), is used to treat HIV-1 infection. LPV is known to have limited oral bioavailability, which may be attributed to its poor aqueous solubility, low efficacy and high first-pass metabolism. Self-nanoemulsifying drug delivery systems (SNEDDS) for LPV have been developed and optimised to counter the current issues.
METHODS: The titration method was used to prepare LPV-loaded SNEDDS (LPV-SNEDDS). Six different pseudo-ternary phase diagrams were constructed to identify the nanoemulsifying region. The developed formulations were chosen in terms of globule size < 100 nm, dispersity ≤ 0.5, dispersibility (Grade A) and% transmittance > 85. Heating-cooling cycle, freeze-thaw cycle, and centrifugation studies were performed to confirm the stability of the developed SNEDDS.
RESULTS: The final LPV-SNEDDS (L-14) droplet size was 58.18 ± 0.62 nm, with polydispersity index, zeta potential, and entrapment efficiency (EE%) values of 0.326 ± 0.005, -22.08 ± 1.2 mV, and 98.93 ± 1.18%, respectively. According to high-resolution transmission electron microscopy (HRTEM) analysis, the droplets in the optimised formulation were < 60 nm in size. The selected SNEDDS released nearly 99% of the LPV within 30 min, which was significantly (p < 0.05) higher than the LPV-suspension in methylcellulose (0.5% w/v). It indicates the potential use of SNEDDS to enhance the solubility of LPV, which eventually could help improve the oral bioavailability of LPV. The Caco-2 cellular uptake study showed a significantly (p < 0.05) higher LPV uptake from the SNEEDS (LPV-SNEDDS-L-14) than the free LPV (LPV-suspension).
CONCLUSION: The LPV-SNEDDS could be a potential carrier for LPV oral delivery.
Role of Artificial Intelligence in Drug Discovery and Target Identification in Cancer

Sharma V, Singh A, Chauhan S, Sharma PK, Chaudhary S, Sharma A, et al.

Curr Drug Deliv, 2023 Sep 05.
PMID: 37670704 DOI: 10.2174/1567201821666230905090621

Drug discovery and development (DDD) is a highly complex process that necessitates precise monitoring and extensive data analysis at each stage. Furthermore, the DDD process is both time-consuming and costly. To tackle these concerns, artificial intelligence (AI) technology can be used, which facilitates rapid and precise analysis of extensive datasets within a limited timeframe. The pathophysiology of cancer disease is complicated and requires extensive research for novel drug discovery and development. The first stage in the process of drug discovery and development involves identifying targets. Cell structure and molecular functioning are complex due to the vast number of molecules that function constantly, performing various roles. Furthermore, scientists are continually discovering novel cellular mechanisms and molecules, expanding the range of potential targets. Accurately identifying the correct target is a crucial step in the preparation of a treatment strategy. Various forms of AI, such as machine learning, neural-based learning, deep learning, and network-based learning, are currently being utilised in applications, online services, and databases. These technologies facilitate the identification and validation of targets, ultimately contributing to the success of projects. This review focuses on the different types and subcategories of AI databases utilised in the field of drug discovery and target identification for cancer.
A Comprehensive Review on the Role of Polymers in Ocular Drug Delivery

Paramjot, Wadhwa S, Sharma A, Singh SK, Vishwas S, Kumar R, et al.

Curr Drug Deliv, 2024;21(1):16-37.
PMID: 36627785 DOI: 10.2174/1567201820666230110140312

Amongst different routes of drug delivery systems, ophthalmic drug delivery still requires a careful investigation and strict parameter measurements because the eyes are one of the most sensitive parts of the body and require special attention. The conventional systems for eyes lead to rapid elimination of formulation and hence very small contact time on the ocular epithelium. The current review article covers various types of polymers used in ocular drug delivery along with their applications/ limitations. Polymers are widely used by researchers in prodrug techniques and as a penetration enhancer in ocular delivery. This article covers the role and use of different polymeric systems which makes the final formulation a promising candidate for ophthalmic drug delivery. The researchers are still facing multiple challenges in order to maintain the therapeutic concentration of the drug in the eyes because of its complex structure. There are several barriers that further restrict the intraocular entry of the drug. In order to remove/reduce such challenges, these days various types of polymers are used for ocular delivery in order to develop different drug carrier systems for better efficacy and stability. The polymers used are highly helpful in increasing residence time by increasing the viscosity at the ocular epithelium layer. Such preparations also get easily permeated in ocular cells. The combination of different polymeric properties makes the final formulation stable with prolonged retention, high viscosity, high permeability, and better bioavailability, making the final formulation a promising candidate for ocular drug delivery.
Synergistic Antibacterial Effect of ZnO Nanoparticles and Antibiotics against Multidrug-Resistant Biofilm Bacteria

Masadeh MM, Bany-Ali NM, Khanfar MS, Alzoubi KH, Massadeh MM, Almomani EM

Curr Drug Deliv, 2024 Jan 12.
PMID: 38231065 DOI: 10.2174/0115672018279213240110045557

BACKGROUND: The misuse of antibiotics leads to a global increase in antibiotic resistance. Therefore, it is imperative to search for alternative compounds to conventional antibiotics. ZnO nanoparticles (Zn NP) are one of these alternatives because they are an effective option to overcome biofilm bacterial cells and a novel way to overcome multidrug resistance in bacteria. The current research study aims to characterize the efficacy of ZnO nanoparticles alone and in combination with other antibacterial drugs against bacterial biofilms.
METHODS: ZnO NPs were prepared by co-precipitation method, and their anti-biofilm and antibacterial activities alone or combined with four types of broad-spectrum antibacterial (Norfloxacin, Colistin, Doxycycline, and Ampicillin) were evaluated against E. coli and S. aureus bacterial strains. Finally, the cytotoxicity and the hemolytic activity were evaluated.
RESULTS: ZnO NPs were prepared, and results showed that their size was around 10 nm with a spherical shape and a zeta potential of -21.9. In addition, ZnO NPs were found to have a strong antibacterial effect against Gram-positive and Gram-negative microorganisms, with a minimum inhibitory concentration (MIC) of 62.5 and 125 μg/mL, respectively. Additionally, they could eradicate biofilmforming microorganisms at a concentration of 125 μg/m. ZnO NPs were found to be non-toxic to erythrocyte cells. Still, some toxicity was observed for Vero cells at effective concentration ranges needed to inhibit bacterial growth and eradicate biofilm-forming organisms. When combined with different antibacterial, ZnO NP demonstrated synergistic and additive effects with colistin, and the MIC and MBEC of the combination decreased significantly to 0.976 μg/mL against planktonic and biofilm strains of MDR Gram-positive bacteria, resulting in significantly reduced toxicity.
CONCLUSION: The findings of this study encourage the development of alternative therapies with high efficacy and low toxicity. ZnO nanoparticles have demonstrated promising results in overcoming multi-drug resistant bacteria and biofilms, and their combination with colistin has shown a significant reduction in toxicity. Further studies are needed to investigate the potential of ZnO nanoparticles as a viable alternative to conventional antibiotics.
Recent Trends and Applications of Nanostructure-based Drug Delivery in Alleviating Chronic Obstructive Pulmonary Disease (COPD)

Lokesh, Gulati N, Saini A, Singh S, Gupta G, MacLoughlin R, et al.

Curr Drug Deliv, 2024 Mar 05.
PMID: 38445696 DOI: 10.2174/0115672018289883240226113353

Chronic Obstructive Pulmonary Disease (COPD), a chronic lung disease that causes breathing difficulties and obstructs airflow from the lungs, has a significant global health burden and affects millions of people worldwide. The use of pharmaceuticals in COPD treatment is aimed to alleviate symptoms, improve lung function, prevent exacerbations, and enhance the overall quality of life for patients. Nanotechnology holds great promise to alleviate the burden of COPD. The main goal of this review is to present the full spectrum of therapeutics based on nanostructures for the treatment and management of COPD, including nanoparticles, polymeric nanoparticles, polymeric micelles, solid-lipid nanoparticles, liposomes, exosomes, nanoemulsions, nanosuspensions, and niosomes. Nanotechnology is just one of the many areas of research that may contribute to the development of more effective and personalized treatment modalities for COPD patients in the future. Future studies may be focused on enhancing the therapeutic effectiveness of nanocarriers by conducting extensive mechanistic investigations to translate current scientific knowledge for the effective management of COPD with little or no adverse effects.