Drug Delivery and Translational Research最新文献

{"title":"Polyelectrolyte complexes based on a novel and sustainable hemicellulose-rich lignosulphonate for drug delivery applications.","authors":"Ioannis Dogaris, Ievgen Pylypchuk, Gunnar Henriksson, Anna Abbadessa","doi":"10.1007/s13346-024-01573-2","DOIUrl":"10.1007/s13346-024-01573-2","url":null,"abstract":"<p><p>Polyelectrolyte complexes (PECs) are polymeric structures formed by the self-assembly of oppositely charged polymers. Novel biomaterials based on PECs are currently under investigation as drug delivery systems, among other applications. This strategy leverages the ability of PECs to entrap drugs under mild conditions and control their release. In this study, we combined a novel and sustainably produced hemicellulose-rich lignosulphonate polymer (EH, negatively charged) with polyethyleneimine (PEI) or chitosan (CH, positively charged) and agar for the development of drug-releasing PECs. A preliminary screening demonstrated the effect of several parameters (polyelectrolyte ratio, temperature, and type of polycation) on PECs formation. From this, selected formulations were further characterized in terms of thermal properties, surface morphology at the microscale, stability, and ability to load and release methylene blue (MB) as a model drug. EH/PEI complexes had a more pronounced gel-like behaviour compared to the EH/CH complexes. Differential scanning calorimetry (DSC) results supported the establishment of polymeric interactions during complexation. Overall, PECs' stability was positively affected by low pH, ratios close to 1:1, and the addition of agar. PECs with higher EH content showed a higher MB loading, likely promoted by stronger electrostatic interactions. The EH/CH formulation enriched with agar showed the best sustained release profile of MB during the first 30 h in a pH-dependent environment simulating the gastrointestinal tract. Overall, we defined the conditions to formulate novel PECs based on a sustainable hemicellulose-rich lignosulphonate for potential applications in drug delivery, which promotes the valuable synergy between sustainability and the biomedical field.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3452-3466"},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory potential of rapamycin-loaded mesoporous silica nanoparticles: pore size-dependent drug loading, release, and in vitro cellular responses.","authors":"Ana M Pérez-Moreno, Carlos J Aranda, María José Torres, Cristobalina Mayorga, Juan L Paris","doi":"10.1007/s13346-024-01575-0","DOIUrl":"10.1007/s13346-024-01575-0","url":null,"abstract":"<p><p>Rapamycin is a potent immunosuppressive drug that has been recently proposed for a wide range of applications beyond its current clinical use. For some of these proposed applications, encapsulation in nanoparticles is key to ensure therapeutic efficacy and safety. In this work, we evaluate the effect of pore size on mesoporous silica nanoparticles (MSN) as rapamycin nanocarriers. The successful preparation of MSN with 4 different pore sizes was confirmed by dynamic light scattering, zeta potential, transmission electron microscopy and N₂ adsorption. In these materials, rapamycin loading was pore size-dependent, with smaller pore MSN exhibiting greater loading capacity. Release studies showed sustained drug release from all MSN types, with larger pore MSN presenting faster release kinetics. In vitro experiments using the murine dendritic cell (DC) line model DC2.4 showed that pore size influenced the biological performance of MSN. MSN with smaller pore sizes presented larger nanoparticle uptake by DC2.4 cells, but were also associated with slightly larger cytotoxicity. Further evaluation of DC2.4 cells incubated with rapamycin-loaded MSN also demonstrated a significant effect of MSN pore size on their immunological response. Notably, the combination of rapamycin-loaded MSN with an inflammatory stimulus (lipopolysaccharide, LPS) led to changes in the expression of DC activation markers (CD40 and CD83) and in the production of the proinflammatory cytokine TNF-α compared to LPS-treated DC without nanoparticles. Smaller-pored MSN induced more substantial reductions in CD40 expression while eliciting increased CD83 expression, indicating potential immunomodulatory effects. These findings highlight the critical role of MSN pore size in modulating rapamycin loading, release kinetics, cellular uptake, and subsequent immunomodulatory responses.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3467-3476"},"PeriodicalIF":8.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porous silicon and silica carriers for delivery of peptide therapeutics.","authors":"Jiachen Yan, Prakriti Siwakoti, Siuli Shaw, Sudeep Bose, Ganesh Kokil, Tushar Kumeria","doi":"10.1007/s13346-024-01609-7","DOIUrl":"10.1007/s13346-024-01609-7","url":null,"abstract":"<p><p>Peptides have gained tremendous popularity as biological therapeutic agents in recent years due to their favourable specificity, diversity of targets, well-established screening methods, ease of production, and lower cost. However, their poor physiological and storage stability, pharmacokinetics, and fast clearance have limited their clinical translation. Novel nanocarrier-based strategies have shown promise in overcoming these issues. In this direction, porous silicon (pSi) and mesoporous silica nanoparticles (MSNs) have been widely explored as potential carriers for the delivery of peptide therapeutics. These materials possess several advantages, including large surface areas, tunable pore sizes, and adjustable pore architectures, which make them attractive carriers for peptide delivery systems. In this review, we cover pSi and MSNs as drug carriers focusing on their use in peptide delivery. The review provides a brief overview of their fabrication, surface modification, and interesting properties that make them ideal peptide drug carriers. The review provides a systematic account of various studies that have utilised these unique porous carriers for peptide delivery describing significant in vitro and in vivo results. We have also provided a critical comparison of the two carriers in terms of their physicochemical properties and short-term and long-term biocompatibility. Lastly, we have concluded the review with our opinion of this field and identified key areas for future research for clinical translation of pSi and MSN-based peptide therapeutic formulations.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3549-3567"},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141179238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cyclosporin A-loaded dissolving microneedles for dermatitis therapy: Development, characterisation and efficacy in a delayed-type hypersensitivity in vivo model.","authors":"Miquel Martínez-Navarrete, Antonio José Guillot, Maria C Lobita, María Carmen Recio, Rosa Giner, Juan Aparicio-Blanco, María Carmen Montesinos, Hélder A Santos, Ana Melero","doi":"10.1007/s13346-024-01542-9","DOIUrl":"10.1007/s13346-024-01542-9","url":null,"abstract":"<p><p>Several drugs can be used for treating inflammatory skin pathologies like dermatitis and psoriasis. However, for the management of chronic and long-term cases, topical administration is preferred over oral delivery since it prevents certain issues due to systemic side effects from occurring. Cyclosporin A (CsA) has been used for this purpose; however, its high molecular weight (1202 Da) restricts the diffusion through the skin structure. Here, we developed a nano-in-micro device combining lipid vesicles (LVs) and dissolving microneedle array patches (DMAPs) for targeted skin delivery. CsA-LVs allowed the effective incorporation of CsA in the hydrophilic DMAP matrix despite the hydrophobicity of the drug. Polymeric matrix composed of poly (vinyl alcohol) (5% w/v), poly (vinyl pyrrolidine) (15% w/v) and CsA-LV dispersion (10% v/v) led to the formation of CsA-LVs@DMAPs with adequate mechanical properties to penetrate the stratum corneum barrier. The safety and biocompatibility were ensured in an in vitro viability test using HaCaT keratinocytes and L929 fibroblast cell lines. Ex vivo permeability studies in a Franz-diffusion cell setup showed effective drug retention in the skin structure. Finally, CsA-LVs@DMAPs were challenged in an in vivo murine model of delayed-type hypersensitivity to corroborate their potential to ameliorate skin inflammatory conditions. Different findings like photon emission reduction in bioluminescence study, normalisation of histological damage and decrease of inflammatory cytokines point out the effectivity of CsA-LVs@DMAPs to treat these conditions. Overall, our study demonstrates that CsA-LVs@DMAPs can downregulate the skin inflammatory environment which paves the way for their clinical translation and their use as an alternative to corticosteroid-based therapies.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3404-3421"},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499354/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discerning computational, in vitro and in vivo investigations of self-assembling empagliflozin polymeric micelles in type-2 diabetes.","authors":"Priti Wagh, Shivani Savaliya, Bhrugesh Joshi, Bhavin Vyas, Ketan Kuperkar, Manisha Lalan, Pranav Shah","doi":"10.1007/s13346-024-01658-y","DOIUrl":"10.1007/s13346-024-01658-y","url":null,"abstract":"<p><strong>Background: </strong>Empagliflozin (EMPA) is an SGLT2 inhibitor, a new class of anti-diabetic medication, indicated for treating type-2 diabetes. Its low permeability, poor solubility and bioavailability limits its use in management of diabetes. The study was aimed to formulate EMPA loaded polymeric micelles (PMs) to overcome these obstacles in oral absorption.</p><p><strong>Methodology: </strong>In silico studies-molecular docking, molecular dynamic simulation (MDS), and quantum chemical calculation were employed to study the interaction of EMPA with different polymers. EMPA loaded TPGS polymeric micelles (EMPA-TPGS-PMs) were formulated by direct dissolution method and characterized in terms of surface morphology, entrapment, particle size, in vitro drug release, and in vitro cytotoxicity (HEK293 cells). In vivo pharmacokinetic and pharmacodynamic studies were also performed.</p><p><strong>Results: </strong>The results suggested a good interaction between TPGS and EMPA with lowest binding energy compared to other polymers. Further MDS results and DFT calculations validated the stable binding of the complex hence TPGS was selected for further wet lab experiments. The EMPA-TPGS complex displayed lower value of Total energy (T.E.) than its individual components, indicating the overall stability of the complex while, the energy band gap (∆E) value lied between the two individual molecules, signifying the better electron transfer between HOMO and LUMO of the complex. Based on the solubility, entrapment and cytotoxicity studies, 5% TPGS was selected for formulating drug loaded micelles. EMPA-TPGS5-PMs presented a size of 9.008 ± 1.25 nm, Polydispersity index (PDI) of 0.254 ± 0.100, a controlled release behaviour upto 24 h. SEM and AFM images of the nanoformulation suggested spherical particles whereas, DSC, and PXRD studies confirmed the loss of crystallinity of EMPA. A 3.12-folds higher AUC and a greater reduction in blood glucose levels was exhibited by EMPA-TPGS5-PMs in comparison to EMPA-SUSP in mice model.</p><p><strong>Conclusion: </strong>EMPA-TPGS-PMs has exhibited better bio absorption and therapeutic effectiveness in diabetes treatment. This improved performance would open the possibility of dose reduction, reduced dosing frequency & dose-related side effects, improving pharmaco-economics and thereby improved overall compliance to the patient. However, this translation from bench to bedside would necessitate studies in higher animals and human volunteers.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3568-3584"},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D-printed Laponite/Alginate hydrogel-based suppositories for versatile drug loading and release.","authors":"Elena Munoz-Perez, J Rubio-Retama, Lorena Cussó, Manoli Igartua, Rosa Maria Hernandez, Edorta Santos-Vizcaino","doi":"10.1007/s13346-023-01506-5","DOIUrl":"10.1007/s13346-023-01506-5","url":null,"abstract":"<p><p>Traditional approaches to solid rectal therapies have halted progress, leading to a continual decline in the use of conventional suppositories. Additive manufacturing techniques have been recently explored as a suitable innovative tool for suppository fabrication. However, little advancement has been made in composition materials for 3D-printed suppository (3DPS) manufacturing and still, conventional vehicles are often used for construct fabrication, hindering the growth in the field. As a novelty, this study unveils a ground-breaking Laponite-alginate hydrogel-based 3DPS. Interestingly, this study proposes a novel approach for loading drugs into the 3DPS employing for the first time the post-printing loading. Thus, a passive loading strategy of molecular models is developed, demonstrating the versatility and capacity to load molecules of different charges and molecular sizes within the matrix systems. This novel strategy allows adapting the load of a wide range of drugs into a single ink, which simplifies and speeds up the 3DPS technological development process for drugs with different physico-chemical properties. Additionally, in this research, a displacement strategy of the three-dimensional Laponite matrices is developed in order to enhance the drug release capacity through the 3DPS and their disintegration capacity, resulting in a significant improvement of the drug diffusion through the hydrogel matrix and a rapid disintegration of the 3DPS. Finally, our study demonstrates that the obtained 3DPS have a suitable in vivo behavior, being non-obstructive and allowing the normal motility of the rats intestine.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3385-3403"},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biodynamers: applications of dynamic covalent chemistry in single-chain polymer nanoparticles.","authors":"Lena Zeroug-Metz, Sangeun Lee","doi":"10.1007/s13346-024-01665-z","DOIUrl":"10.1007/s13346-024-01665-z","url":null,"abstract":"<p><p>Dynamic Covalent Chemistry (DCC) enables the development of responsive molecular systems through the integration of reversible bonds at the molecular level. These systems are thermodynamically stable and capable of undergoing various molecular assemblies and transformations, allowing them to adapt to changes in environmental conditions like temperature and pH. Introducing DCC into the field of polymer science has led to the design of Single-Chain Nanoparticles (SCNPs), which are formed by self-folding via intramolecular crosslinking mechanisms. Defined by their adaptability, SCNPs mimic biopolymers in size and functionality. Biodynamers, a subclass of SCNPs, are specifically designed for their stimuli-responsive and tunable, dynamic properties. Mimicking complex biological structures, their scope of application includes target-specific and pH-responsive drug delivery, enhanced cellular uptake and endosomal escape. In this manuscript, we discuss the integration of DCC for the design of SCNPs, focusing particularly on the characteristics of biodynamers and their biomedical and pharmaceutical applications. By underlining their potential, we highlight the factors driving the growing interest in SCNPs, providing an overview of recent developments and future perspectives in this research field.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3599-3607"},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on ultrasound-enhanced molecular transport in articular cartilage.","authors":"Xiaoyu Wang, Yansong Tan, Lilan Gao, Hong Gao","doi":"10.1007/s13346-024-01695-7","DOIUrl":"10.1007/s13346-024-01695-7","url":null,"abstract":"<p><p>Local intra-articular administration with minimal side effects and rapid efficacy is a promising strategy for treating osteoarthritis(OA). Most drugs are rapidly cleared from the joint space by capillaries and lymphatic vessels before free diffusion into cartilage. Ultrasound, as a non-invasive therapy, enhances molecular transport within cartilage through the mechanisms of microbubble cavitation and thermal effects. This study investigated the mass transfer behavior of solute molecules with different molecular weights (479 Da, 40 kDa, 150 kDa) within porcine articular cartilage under low-frequency ultrasound conditions of 40 kHz and ultrasound intensities of 0.189 W/cm² and 0.359 W/cm². The results revealed that under the conditions of 0.189 W/cm² ultrasound intensity, the mass transfer concentration of solute molecules were higher compared to passive diffusion, and with an increase in ultrasound intensity to 0.359 W/cm², the mass transfer effect within the cartilage was further enhanced. Ultrasound promotes molecular transport in different layers of cartilage. Under static conditions, after 2 h of mass transfer, the concentration of small molecules in the superficial layer is lower than that in the middle layer. After applying ultrasound at 0.189 W/cm², the molecular concentration in the superficial layer significantly increases. Under conditions of 0.359 W/cm², after 12 h of mass transfer, the concentration of medium and large molecules in the deep layer region increased by more than two times. In addition, this study conducted an assessment of damage to porcine articular cartilage under ultrasound exposure, revealing the significant potential of low-frequency, low-intensity ultrasound in drug delivery and treatment of OA.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3621-3639"},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141981964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleic acid-loaded poly(beta-aminoester) nanoparticles for cancer nano-immuno therapeutics: the good, the bad, and the future.","authors":"J Rodrigo Magaña Rodriguez, Marta Guerra-Rebollo, Salvador Borrós, Cristina Fornaguera","doi":"10.1007/s13346-024-01585-y","DOIUrl":"10.1007/s13346-024-01585-y","url":null,"abstract":"<p><p>Immunotherapy has emerged as a promising approach to cancer treatment, offering improved survival rates and enhanced patients' quality of life. However, realizing the full potential of immunotherapy in clinical practice remains a challenge, as there is still plenty of room for modulating the complexity of the human immune system in favor of an antitumor immunogenicity. Nanotechnology, with its unique properties, holds promise in augmenting the efficacy of cancer immunotherapies in biotherapeutic protection and site- and time-controlled delivery of the immune modulator biologicals. Polymeric nanoparticles are promising biomaterials among different nanocarriers thanks to their robustness, versatility, and cost-efficient design and production. This perspective paper overviews critical concepts in nanometric advanced delivery systems applied to cancer immunotherapy. We focus on a detailed exploration of the current state of the art and trends in using poly(beta-aminoester) (pBAE) polymers for nucleic acid-based antitumor immunotherapies. Through different examples of the use of pBAE polymers reported in the literature, we revise the main advantages these polymers offer and some challenges to overcome. Finally, the paper provides insights and predictions on the path toward the clinical implementation of cancer nano-immunotherapies, highlighting the potential of pBAE polymers for advancements in this field.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3477-3493"},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11499432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Formulation of protein-loaded nanoparticles via freeze-drying.","authors":"Matilde Durán-Lobato, Sulay Tovar, Tadeu de Oliveira Diz, Miguel Chenlo, Clara V Álvarez, María José Alonso","doi":"10.1007/s13346-024-01712-9","DOIUrl":"10.1007/s13346-024-01712-9","url":null,"abstract":"<p><p>Several nanotechnology-based formulation strategies have been reported for the oral administration of biological drugs. However, a prerequisite often overlooked in developing these formulations is their adaptation to a solid dosage form. This study aimed to incorporate a freeze-drying step, using either mannitol or sucrose laurate (SLAE), into the formulation of new insulin-zinc nanocomplexes to render them resistant to intestinal fluids while maintaining a high protein loading. The resulting freeze-dried insulin-zinc nanocomplexes exhibited physicochemical properties consistent with the target product profile, including a particle size of ∼ 100 nm, a zeta potential close to neutrality (∼ -15 mV) and a high association efficiency (> 90%). Importantly, integrating the freeze-drying step in the formulation significantly improved the colloidal stability of the system and preserved the stability of the insulin molecules. Results from in vitro and in vivo studies indicated that the insulin activity remained fully retained throughout the entire formulation and freeze-drying processes. In brief, we present a novel protein formulation strategy that incorporates a critical freeze-drying step, resulting in a dry powder enabling efficient protein complexation with zinc and optimized for oral administration.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3640-3653"},"PeriodicalIF":5.7,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}