Organic and Biogenic Nanocarriers as Bio-Friendly Systems for Bioactive Compounds’ Delivery: State-of-the Art and Challenges

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TL;DR

This comprehensive review examines organic and biogenic nanocarriers (OBNs) for delivering bioactive compounds, highlighting their potential to improve stability, bioavailability, and targeted delivery. The paper emphasizes green strategies, including valorization of bio-wastes and use of living systems, to develop biocompatible and biodegradable nanocarriers. Key challenges include scaling up production, controlling physicochemical properties, and ensuring safety, with future directions focusing on multifunctional, biomimetic, and sustainable nanocarrier designs.

Full summary

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**Background:** Nanotechnology has revolutionized drug delivery through nanocarriers (NCs) that encapsulate bioactive compounds (BCs), protecting them from degradation and improving their bioavailability and therapeutic efficacy. Organic and biogenic nanocarriers (OBNs) are particularly attractive due to their biocompatibility, biodegradability, and potential for green synthesis. This review provides a comprehensive overview of OBNs for BC delivery, covering the past two decades of research, with a focus on green strategies, including the valorization of bio-wastes and the use of living systems.

**Methods:** The paper is a narrative review that synthesizes information from the scientific literature, primarily from the Web of Science database, on OBNs. It categorizes OBNs into polymeric, carbon-based, biological (lipid-based, biopolymer-based, cell-derived), and hybrid nanocarriers. The review discusses various classes of BCs (e.g., phytochemicals, vitamins, proteins), their therapeutic roles, and the challenges associated with their delivery. It also covers characterization techniques (e.g., DLS, TEM, FTIR, antioxidant assays) and the fate of OBNs in the body, including opsonization and ADME profiles.

**Key Results:** The review identifies several key findings: - **Polymeric nanocarriers** (e.g., PLGA, dendrimers) offer high stability and can encapsulate both hydrophilic and hydrophobic drugs. For example, curcumin nanomicelles using polyvinyl caprolactam–polyvinyl acetate–polyethylene glycol showed improved in vivo corneal permeation compared to free curcumin. - **Carbon-based nanomaterials** (e.g., carbon nanotubes, fullerenes, carbon quantum dots) have unique properties but require functionalization to reduce toxicity. For instance, single-walled carbon nanotubes loaded with resveratrol (CNT-RSV) showed reduced cytotoxicity and enhanced antioxidant activity compared to RSV or CNT alone. - **Lipid-based nanocarriers** (e.g., liposomes, niosomes, solid lipid nanoparticles) are the most widely used due to their biocompatibility and ability to carry both hydrophilic and hydrophobic compounds. Liposomes encapsulating vitamin C retained 50% activity after 50 days at 4°C, versus 19 days for free vitamin C. - **Biopolymer-based nanocarriers** (e.g., albumin, chitosan, zein) are biodegradable and can be functionalized for targeted delivery. For example, human serum albumin nanoparticles encapsulating paclitaxel-pentadecanoic acid conjugate (HPTX NPs) showed reduced systemic toxicity compared to Taxol and good antitumor activity against four human cancer cell lines. - **Cell-derived nanocarriers** (e.g., red blood cell membrane-coated nanoparticles, yeast cells) offer stealth properties and low immunogenicity. Ursolic acid-loaded nanoparticles wrapped with red blood cell membrane (UrANPs-RBCM) showed high stability and anticancer effects against non-small-cell lung cancer cells. - **Green strategies** include biomimetics, self-assembly, and valorization of bio-wastes (e.g., fruit peels, shellfish waste, hair). For example, carbon nanostructures were synthesized from onion peels and tannin polyphenols from Mimosa. - **Challenges** include scaling up production, controlling size and shape uniformity, ensuring stability during storage, and addressing toxicity concerns. For instance, nanoparticles around 40–70 nm can damage the liver and heart muscle in vivo.

**Clinical Implications:** OBNs have significant potential for clinical applications in drug delivery, cancer therapy, and regenerative medicine. They can improve the bioavailability and stability of BCs, enable targeted delivery, and reduce systemic toxicity. For example, curcumin-loaded mesoporous polydopamine nanoparticles (CUR-mPDA NPs) were used for prevention and treatment of radiation pneumonitis. However, clinical translation faces hurdles such as regulatory challenges, lack of standardization, and need for comprehensive safety assessments. Future directions include developing multifunctional nanocarriers for combination therapy, biomimetic designs for improved targeting, and sustainable production methods using bio-wastes.