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Biomaterial-Based Nanoencapsulation Systems for Drug Protection and Controlled Release

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 7902

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Dr. Oscar E. Pérez

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Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), UBA-CONICET, Buenos Aires 1428, Argentina
Interests: nanotechnology; biomaterial; nanoencapsulation; controlled release; bioavailability

Special Issue Information

Dear Colleagues,

The concept of nanoencapsulation falls within the area of nanotechnology, which is defined as any technology related to materials, systems, and processes that operate at a scale of ≤100 nm, although, in practice, a maximum limit of 500 nm is accepted. Nanoencapsulation encompasses processes that have the advantage of providing protection to the component of interest, drugs, and bioactive compounds. Nanoencapsulation techniques and processes have emerged as promising tools in the pharmaceutical and nutraceutical sectors. An encapsulated bioactive would be trapped by a system that can preserve it from degradation, increasing its solubility and its bioavailability with the possibility of exerting a controlled release.

Biopolymers, i.e., polysaccharides, lipids, and proteins, are promising materials for constructing encapsulation matrices due to their characteristics such as abundance, biocompatibility, and non-toxicity. Furthermore, nanostructures could act as a versatile tool to enhance the therapeutic index of drugs, the bioavailability of which depends on the stability of the drug or bioactive in the oral, gastric, and intestinal environment, its solubility and mode of absorption, and, subsequently, its reach to the target organ.

Dr. Oscar E. Pérez
Guest Editor

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Keywords

nanostructures
nanoencapsulation
drugs/bioactive compounds
biopolymer materials
controlled release
bioavailability
nanoproducts

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Published Papers (7 papers)

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Research

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24 pages, 11841 KB

Open AccessArticle

Harnessing Folate-Mediated PSMA Targeting for Precision Therapy: An Intelligent Liposomal Nanoplatform Against Prostate Cancer

by Youlong Hai, Jiayi Ma, Xuehao Yu, Kun Zheng, Yu Huang, Kai Ni and Xiaoyong Hu

Pharmaceutics 2026, 18(2), 244; https://doi.org/10.3390/pharmaceutics18020244 - 15 Feb 2026

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Abstract

Background: Prostate cancer is a leading malignancy among males, and conventional chemotherapy is often limited by insufficient tumor selectivity and systemic toxicity. Prostate-specific membrane antigen (PSMA), which is highly expressed on prostate cancer cells, represents a promising target for precision drug delivery. In this study, we developed a folate-modified, PSMA-targeting nanoliposome loaded with docetaxel (DFL) to enhance tumor specificity and therapeutic efficacy. Methods: DFL was prepared using a thin-film hydration–sonication method and characterized through physicochemical analyses. Cellular uptake and cytotoxicity were evaluated in PSMA-high LNCaP cells, with PSMA knockdown used to assess target-dependent internalization. Antitumor efficacy was examined with a microfluidic system and LNCaP xenograft nude mice, and safety was evaluated by measuring hepatic and renal biomarkers and performing histopathological analysis of major organs. Results: DFL demonstrated favorable physicochemical properties and significantly enhanced cellular uptake and cytotoxicity in LNCaP cells relative to control formulations. PSMA knockdown markedly attenuated cellular sensitivity to DFL, confirming PSMA-dependent internalization. A 3D microfluidic perfusion platform further corroborated robust and selective DFL uptake under dynamic flow conditions, thereby strengthening the translational relevance of the targeting effect beyond static cultures. In vivo, DFL substantially inhibited tumor progression in LNCaP xenograft models, reducing both tumor volume and weight by more than 50%. TUNEL assays showed increased apoptosis, and immunohistochemistry revealed reduced Ki-67 expression with concomitant upregulation of Caspase-3. No significant alterations in hepatic or renal biomarkers were observed, and histopathological evaluation demonstrated no treatment-associated lesions in major organs. Conclusions: A folate-modified, PSMA-targeting docetaxel nanoliposome was successfully developed, demonstrating enhanced tumor-specific drug delivery and improved antitumor activity with favorable biocompatibility in preclinical models. DFL represents a promising nanomedicine strategy for the precision chemotherapy of prostate cancer. Full article

(This article belongs to the Special Issue Biomaterial-Based Nanoencapsulation Systems for Drug Protection and Controlled Release)

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27 pages, 5396 KB

Open AccessArticle

Development and Evaluation of Scaffolds Based on Perch Collagen–Hydroxyapatite for Advanced Synthetic Bone Substitutes

by Alina Elena Coman, Ana Maria Rosca, Maria Minodora Marin, Madalina Georgiana Albu Kaya, Raluca Gabor, Catalina Usurelu, Mihaela Violeta Ghica, Laurentiu Dinca and Irina Titorencu

Pharmaceutics 2026, 18(1), 33; https://doi.org/10.3390/pharmaceutics18010033 - 26 Dec 2025

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Abstract

Background/Objectives: Bone defects remain widespread. Type I collagen–hydroxyapatite composites suit bone engineering by mimicking matrix structure, making them pertinent materials for bone tissue engineering across a range of defect types. Their application is well aligned with non-load-bearing conditions, while use in load-bearing sites requires mechanical properties that meet the demands of those environments. Marine collagen offers a low-cost source from processing by-products. This work aimed to develop perch collagen–hydroxyapatite scaffolds for bone tissue engineering. Methods: Composites with COLL:HAp ratios of 100:0, 50:50, 40:60, and 30:70 were prepared. After crosslinking and freeze-drying, porosity and water absorption were examined. SEM and X-EDS assessed morphology and elemental distribution. FT-IR confirmed the chemical composition. Compression tests evaluated mechanical behavior. Cell viability and colonization assessed the biological performance. Biodegradability, thermal stability, and antimicrobial activity were also determined. Results: FT-IR confirmed the characteristic absorption bands of both components. SEM and swelling behavior showed porous, interconnected structures with uniform hydroxyapatite dispersion. X-EDS indicated Ca/P ratios consistent with hydroxyapatite. Thermal analysis demonstrated scaffold stability. Compression tests showed mechanical resistance for all the scaffolds, with stiffness increasing with the inorganic content. Perch collagen enhanced biological functionality, supporting osteoblast viability and colonization. Biodegradation gradually proceeded. Antibacterial activity against the tested pathogens was detectable, though moderate. Conclusions: The developed scaffolds combined structural stability, controlled degradation, and favorable cell response, constituting a viable and promising candidate for applications in bone tissue engineering. Full article

(This article belongs to the Special Issue Biomaterial-Based Nanoencapsulation Systems for Drug Protection and Controlled Release)

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17 pages, 1741 KB

Open AccessArticle

Fabrication and Characterization of Curcumin-Complexed Nanoparticles Using Coconut Protein Nanoparticles

by Leila Ziaeifar, Maryam Salami, Gholamreza Askari, Zahra Emam-Djomeh, Raimar Loebenberg, Michael J Serpe and Neal M. Davies

Pharmaceutics 2025, 17(10), 1247; https://doi.org/10.3390/pharmaceutics17101247 - 24 Sep 2025

Cited by 1 | Viewed by 986

Abstract

Background/Objectives: Curcumin (Cur) has various biological properties, including anti-microbial, antioxidant, anticancer, anti-diabetic, anticarcinogenic, antitumor, and anti-inflammatory activities. However, using Cur in functional food products is challenging because of its low solubility in an aqueous environment, rapid degradation, and low bioavailability. Nanostructure delivery systems provide a high surface area to volume ratio and sustainable release properties. Methods: Coconut protein nanoparticles (CPNPs) have been fabricated through heat treatment at 85 °C and pH 2 for 5 h. The formation of CPNP-Cur was used to improve Cur solubility, followed by antioxidant activity at neutral pH in an aqueous solution. Results: The maximum efficiency and loading capacity of Cur in CPNP were 96.6% and 19.32 µg/mg protein, respectively. Scanning electron microscopy indicated the spherical and organized shape of CPNP with a small size of 80 nm. The fluorescence quenching of CPNP-Cur confirmed the potential of Cur to bind to the tryptophane and tyrosine residues in CPNP. The structural properties of CPNP and CPNP-Cur were investigated using FTIR and X-ray diffraction. The antioxidant activity of samples, measured with the ABTS radical scavenging method, demonstrated that the antioxidant capacity of the aqueous solution of Cur was significantly enhanced through the encapsulation into CPNP. The steady release of Cur was observed in the simulated gastrointestinal tract, and the percentage of the cumulative release increased up to 29.2% after 4 h. Conclusions: Our findings suggest that CPNP was a suitable nanocarrier for Cur due to improved antioxidant activity and controlled release behavior. These results are valuable for the development of coconut protein nanoparticles to use as a novel nano-delivery system of bioactive components. Full article

(This article belongs to the Special Issue Biomaterial-Based Nanoencapsulation Systems for Drug Protection and Controlled Release)

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17 pages, 2295 KB

Open AccessArticle

Solid Tranilast Nanocrystal-Loaded Cationic Contact Lenses for Sustained Ocular Drug Delivery

by Shinichiro Kobayakawa, Toru Matsunaga, Hiroko Otake, Shiori Hino, Fumihiko Ogata, Manju Misra, Kazutaka Kanai, Naohito Kawasaki and Noriaki Nagai

Pharmaceutics 2025, 17(10), 1240; https://doi.org/10.3390/pharmaceutics17101240 - 23 Sep 2025

Cited by 1 | Viewed by 961

Abstract

Background/Objectives Conventional eye drops are the primary therapeutic option for ocular diseases; however, their clinical utility is hindered by several drawbacks, including limited bioavailability and suboptimal patient compliance. To overcome these challenges, we designed a sustained-release contact lens (CL) device loaded with tranilast (TRA) and determined whether the TRA-laden CL could provide sustained drug delivery to the lacrimal fluid and aqueous humor. Methods TRA nanocrystals were prepared using the bead-milling approach. Using three types of CLs (nonionic, anionic, and cationic), we prepared TRA-laden CLs by employing a combination of solid TRA nanocrystals and soaking methods under high-temperature and high-pressure conditions in an autoclave (the hThP method). Male Japanese albino rabbits (2–3 kg) were used to evaluate the CLs. Results Bead milling reduced the size of the solid TRA nanoparticles (STNs) to approximately 35–180 nm. The TRA-laden cationic CLs prepared using STNs and the hThP method contained a higher amount of TRA than those prepared using the corresponding conventional soaking method. The CLs prepared using the hThP method remained transparent after drug loading. Compared with nonionic and anionic CLs, cationic CLs had the highest drug-loading capacity and allowed for sustained drug release. Moreover, STNs were observed in the released TRA, with no corneal damage or light scattering detected in the rabbits’ eyes. TRA-laden cationic CLs prepared using the hThP method achieved sustained and higher drug delivery into the lacrimal fluid and aqueous humor than those prepared using the conventional soaking method. Conclusions Our findings suggest that TRA-laden cationic CLs prepared using STNs and the hThP method can overcome the challenges associated with the conventional soaking method, including low drug uptake and high burst release. Full article

(This article belongs to the Special Issue Biomaterial-Based Nanoencapsulation Systems for Drug Protection and Controlled Release)

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19 pages, 4026 KB

Open AccessArticle

Synthesis of Terminal-Alkylated PEGs with Imine Spacer to Form Iminium Mono-Ion Complexes for pDNA Delivery into Skeletal Muscle

by Riku Oba, Yoko Endo-Takahashi, Yoichi Negishi and Shoichiro Asayama

Pharmaceutics 2025, 17(8), 1054; https://doi.org/10.3390/pharmaceutics17081054 - 13 Aug 2025

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Abstract

Background/Objectives: To design the pDNA delivery carrier for delivery into skeletal muscle, a total of twelve terminal-alkylated PEGs (Cx-I-PEGy) with four alkyl groups of different carbon numbers (Cx: x = 4, 8, 12, 16) modified via an imine spacer at the ends of three methoxy PEGs of different molecular weights (PEGy: y = 500, 2k, 5k) have been synthesized. Methods: Among them, four Cx-I-PEG5k formed an imine-mediated complex formation with pDNA, as assessed by agarose gel electrophoresis, defined as an iminium mono-ion complex (I-MIC) without multivalent electrostatic interaction by minimizing potential toxic cations. Results: Most resulting I-MICs maintained the flexible structure of pDNA and promoted the binding to pDNA. The expression of pDNA by intramuscular injection with the resulting I-MICs was the highest by using I-MICs with C4-I-PEG5k and was observed extensively by the in vivo imaging system (IVIS). Conclusions: These results suggest that the I-MICs with C4-I-PEG5k are promising for pDNA transfection into skeletal muscle, offering the alkyl iminium for the pDNA binding group to demonstrate the factor of pDNA’s flexible structure as one of the key parameters for in vivo local pDNA transfection. Full article

(This article belongs to the Special Issue Biomaterial-Based Nanoencapsulation Systems for Drug Protection and Controlled Release)

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26 pages, 11210 KB

Open AccessArticle

Perspectives on the pH-Influenced Design of Chitosan–Genipin Nanogels for Cell-Targeted Delivery

by Julieta D. Glasman, Agustina Alaimo, Cecilia Samaniego López, María Edith Farías, Romina B. Currá, Diego G. Lamas and Oscar E. Pérez

Pharmaceutics 2025, 17(7), 876; https://doi.org/10.3390/pharmaceutics17070876 - 3 Jul 2025

Cited by 1 | Viewed by 1536

Abstract

Background: Chitosan (CS) crosslinked with genipin (GNP) provides a mild, non-toxic route to generate nanogels (NGs) with enhanced integrity and colloidal stability. Objectives: To develop and characterise CS-GNP NG as a novel platform for targeted cellular delivery, optimising design through physicochemical characterisation and biocompatibility evaluation. Methods: NGs were synthesised under optimised conditions by adjusting the pH of the CS solution, followed by high-intensity ultrasound (HIUS) to achieve disaggregation. Physicochemical characterisation was carried out using UV-Vis spectroscopy, FTIR, dynamic light scattering (DLS), and scanning electron microscopy (SEM). Rheological studies and SAXS analysis assessed structural properties. Biocompatibility was evaluated via MTT assay, and internalisation was monitored by fluorescence microscopy on mammalian cell lines. Results: NG formation was highly pH-dependent, with optimal configuration at pH 4.5, yielding stable, uniformly sized particles (~200 nm, ζ-potential +29 mV). Kinetic modelling showed a sigmoidal formation pattern, suggesting nucleation, growth, and stabilisation. FTIR confirmed covalent bonding between CS and GNP via primary amide bonds and Schiff bases. Rheology indicated pseudoplastic behaviour, and SAXS revealed a compact network formation. Biocompatibility assays confirmed non-cytotoxicity below 100 µg/mL and efficient cellular uptake. Conclusions: This study presents a rapid, reproducible protocol for generating colloidally stable, biocompatible NGs suitable for drug delivery. Full article

(This article belongs to the Special Issue Biomaterial-Based Nanoencapsulation Systems for Drug Protection and Controlled Release)

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Review

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27 pages, 890 KB

Open AccessReview

Nanotechnology-Enabled Precision Therapy for Lung Cancer in Never-Smokers

by Cristian Cojocaru, Adina Magdalena Țurcanu, Ruxandra Cojocaru and Elena Cojocaru

Pharmaceutics 2026, 18(2), 161; https://doi.org/10.3390/pharmaceutics18020161 - 26 Jan 2026

Viewed by 650

Abstract

Lung cancer in never-smokers (LCINS) represents a distinct clinical entity driven by dominant oncogenic alterations and characterized by a low tumor mutational burden. Although tyrosine kinase inhibitors (TKIs) achieve high initial response rates, their long-term efficacy is limited by suboptimal pharmacokinetics, restricted central nervous system (CNS) penetration, tumor microenvironment barriers, and acquired resistance. In this review, we critically assess the current state of nanotechnology-assisted drug delivery systems for LCINS, with a primary focus on how rationally designed nanocarriers can overcome biological barriers, enable molecular subtype-specific therapeutic strategies, and address mechanisms that limit clinical efficacy and durability of response. We conducted a structured literature search using PubMed and Web of Science (January 2022 to November 2025), focusing on primary studies reporting the preparation, physicochemical properties, and therapeutic performance of nanocarriers in in vitro and in vivo models, as well as available pharmacokinetic and clinical data. LCINS is characterized by inefficient vasculature, high extracellular matrix density, active efflux transporters, and immunosuppressive niches, and is frequently complicated by brain metastases. Nanocarrier-based platforms can enhance aqueous solubility, prolong systemic circulation, and improve tumor or CNS targeting. Co-delivery systems combining TKIs with nucleic acid-based therapeutics, together with stimuli-responsive platforms, offer the potential for simultaneous modulation of multiple oncogenic pathways and partial mitigation of resistance mechanisms. In summary, nanotechnology provides a promising strategy to improve both the efficacy and specificity of targeted therapies in LCINS. Successful clinical translation will depend on biologically aligned carrier–payload combinations, scalable and reproducible manufacturing processes, and biomarker-guided patient selection. Full article

(This article belongs to the Special Issue Biomaterial-Based Nanoencapsulation Systems for Drug Protection and Controlled Release)

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