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Drug Carriers Production Processes for Innovative Human Applications

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A special issue of Processes (ISSN 2227-9717). This special issue belongs to the section "Pharmaceutical Processes".

Deadline for manuscript submissions: 31 December 2024 | Viewed by 26378

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Dr. Paolo Trucillo

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Department of Chemical, Material and Industrial Production Engineering, University of Naples Federico II, Piazzale V. Tecchio, 80-80125 Napoli, Italy
Interests: liposomes; microparticles; targeted delivery; pharmaceuticals; stimuli induced delivery; process scale-up; process economic analysis
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Dear Colleagues,

Drug carriers are special tools used for the transportation and preservation of molecules for several pharmaceutical, cosmetic and nutraceutical applications. The main advantage of carriers is their capability of incorporating drugs, enhancing their bioavailability and selectivity; thus, reducing side effects to humans.

Drug carriers can be classified according to their nature, shape and materials of production. Nanoparticles are spherical objects, generally employed in pharmaceutical applications, such as gene therapy, the delivery of proteins, dietary supplements, vitamin, antibiotics and vaccines. Nanotubes are hollow cylinders of carbon, used to treat carcinogenic cells or tissues. Dendrimers are more complex arrays of carriers, with a branched shape used for the simultaneous and efficient transportation of drugs. Liposomes are spherical vesicles composed of an inner aqueous core surrounded by a double layer of phospholipids, particularly useful since they are biocompatible with human cells. Polymersomes are spherical vesicles obtained with a polymer coating, which guarantees a controlled and delayed drug release. Instead, niosomes are spherical vesicles composed of nonionic surfactant active agents. These are only some examples of carriers used in pharmaceutical, cosmetic and nutraceutical applications; all of them require great contemplation by the scientific community.

Drug delivery can be performed through several types of administration routes: active or passive. In this Special Issue, all of the following kinds of drug delivery routes are acceptable as topics for innovative research papers or reviews: ocular, oral, transdermal, nasal, pulmonary, vaginal and urinary, subcutaneous, delivery by patches and microelectromechanical systems (MEMS).

Several processes have been proposed for the production of drug carriers in order to improve their properties, such as nanometric dimensions, encapsulation efficiency, the reduction in solvent residue, sterility and stability over time. Therefore, carriers’ main properties and characteristics may vary significantly, depending on the production processes used. In this Special Issue, we welcome the presentation of novel methodologies for the production of drug carriers, as well as new potential findings regarding the physics of the problem. Moreover, the innovation of products provided by conventional methods as well as innovative processes and on products are also going to be taken under great consideration. Finally, the economic analysis of the process of productive plants is also an aim of this Special Issue, as well as the processes’ environmental impact.

Dr. Paolo Trucillo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Processes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2400 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

nanoparticles
nanocapsules
nanospheres
liposomes
foams
carbon nanotubes
dendrimers
cubosomes
niosomes
hydrogels
conventional processes
drug delivery systems
modeling of drug delivery
high-pressure systems
supercritical processes
economic analysis
environmental impact of processes

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Published Papers (10 papers)

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Research

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19 pages, 20212 KiB

Open AccessArticle

Carboxymethyl-Cellulose-Based Hydrogels Incorporated with Cellulose Nanocrystals Loaded with Vitamin D for Controlled Drug Delivery

by Nathália da Cunha Silva, Carla Jeany Teixeira Silva, Max Pereira Gonçalves and Fernanda G. L. Medeiros Borsagli

Processes 2024, 12(7), 1437; https://doi.org/10.3390/pr12071437 - 9 Jul 2024

Viewed by 839

Abstract

Currently, the development of innovative materials for the treatment of various diseases is highly interesting and effective. Additionally, in recent years, environmental changes, including the search for a sustainable world, have become the main goal behind developing sustainable and suitable materials. In this context, this research produced innovative hydrogels that incorporate cellulose nanocrystals and nanofibres from underutilised fibres from a semiarid region of Brazil; the hydrogels were loaded with vitamin D to evaluate controlled drug release for the treatment of diverse diseases. Spectroscopic (FTIR, Raman, UV–VIS), X-ray diffraction, zeta potential and morphology (SEM, TEM) analyses were used to characterise these hydrogels. In addition, biocompatibility was assessed using a resazurin assay, and the in vitro kinetic accumulative release of vitamin D was measured. The results showed that nanocrystals and nanofibres changed the structure and crystallinity of the hydrogels. In addition, the chemical groups of the hydrogels were red- and blueshifted in the FTIR spectra when the nanocrystals, nanofibres and vitamin D were incorporated. Moreover, the nanocrystals and nanofibres were homogeneously spread into the hydrogel when vitamin D was loaded into the hydrogel matrix. Furthermore, the cytotoxicity was greater than 90%. Additionally, the in vitro accumulative kinetic data of vitamin D release were robust (close to 40 ng·mL⁻¹), with equilibrium being reached in the first 30 min. These results confirm the potential of using these hydrogels as therapeutic biomaterials for diverse diseases and problems in humans, mainly in women, who are the most harmed by vitamin D deficiency. Full article

(This article belongs to the Special Issue Drug Carriers Production Processes for Innovative Human Applications)

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14 pages, 2782 KiB

Open AccessArticle

The Improved Cytotoxic Capacity of Functionalized Nanodiamonds with Metformin in Breast and Ovarian Cancer Cell Lines

by Lucero Evelia Acuña-Aguilar, Alain Salvador Conejo-Dávila, Mario Miki-Yoshida, Olga N. Hernández-de la Cruz, Gricelda Sánchez-Sánchez, César López-Camarillo, Joan Sebastian Salas-Leiva, Erasto Armando Zaragoza-Contreras, Reyna Reyes-Martínez and Erasmo Orrantia-Borunda

Processes 2023, 11(9), 2616; https://doi.org/10.3390/pr11092616 - 2 Sep 2023

Cited by 2 | Viewed by 1630

Abstract

Nanodiamonds (ND-COOH) are used as drug delivery systems because of their attractive properties, as they allow for optimized transport of therapeutic agents in cellular models. Metformin (MET) is a drug used in diabetes mellitus therapy and exhibits anti-cancer properties. In this study, dispersed nanodiamonds were functionalized with metformin by directly binding them to 1,6-hexanediol (ND-MET), and their effects on the cytotoxicity of breast and ovarian cancer cells were evaluated in vitro. A simple synthesis of ND-MET was performed and characterized using FT-IR, XPS, Boehm titration, RAMAN, XDR, TEM, and dynamic light scattering (DLS). Data showed an increased intensity of the C-N bond band, indicating the presence of metformin in ND-MET. We detected signals at 1427 cm⁻¹ and 1288 cm⁻¹ corresponding to the C-N and C-H bonds, and adsorptions at 1061 cm⁻¹ and 3208 cm⁻¹ corresponding to the N-O and N-H bonds, respectively. The deconvolution of the C1s binding energy was also found at 286.24 eV. The biological effects of ND-MET were tested in both SKOV3 ovarian cancer and Hs-578T and MDA-MB-231 triple-negative breast cancer cell lines. In SKOV3 cells, the IC₅₀ for the ND-MET complex was 35 ± 14 µg/mL, while for Hs-578T and MDA-MB-231 breast cancer cells, the IC₅₀ for ND-MET was 759 ± 44 µg/mL and 454 ± 49 µg/mL, respectively. Our data showed that ND-MET could be used as an intracellular delivery system for metformin in cancer cells. Cell viability assays evidenced a reduced viability of all cell lines in a time and dose-dependent manner, with a significant sensitivity observed in SKOV3 ovarian cancer cells treated with ND-MET. Full article

(This article belongs to the Special Issue Drug Carriers Production Processes for Innovative Human Applications)

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13 pages, 2672 KiB

Open AccessArticle

Development of Tea Tree Oil Based Nanoemulgel Loaded with Azithromycin for Enhancing the Antibacterial Activity

by Nasrin E. Khalifa, Marwa H. Abdallah, Hanaa A. Elghamry, Weam M. A. Khojali, El-Sayed Khafagy, Hemat El-Sayed El-Horany and Seham Shawky

Processes 2023, 11(6), 1836; https://doi.org/10.3390/pr11061836 - 17 Jun 2023

Cited by 3 | Viewed by 1827

Abstract

Azithromycin (AZ) is an azalide macrolide antibiotic that is frequently employed for treating bacterial skin infections. It suffers from limited oral bioavailability, which results from incomplete absorption or extensive first-pass metabolism. Therefore, preparing azithromycin formulations for topical administration is highly recommended to avoid first-pass metabolism and to boost the concentration of the drug on the skin. The objective of our investigation was to formulate and evaluate the efficacy of AZ-loaded nanoemulgel as an antimicrobial drug. The physical appearance, spreadability, viscosity, particle size, in vitro drug release, ex vivo permeation investigations, and antimicrobial efficiency of the prepared formulations were evaluated. The prepared formulation loaded with AZ exhibited good physical quality. AZ-loaded nanoemulgel had a greater ex vivo drug permeation across rabbit skin than other formulations (AZ-loaded gel and AZ-loaded emulgel), revealing improved drug permeation and greater transdermal flux in addition to enhanced antibacterial efficacy (p < 0.05). Overall, our findings imply that tea-tree-oil-based nanoemulgel would be a promising delivery system for enhancing the antimicrobial efficiency of azithromycin. Full article

(This article belongs to the Special Issue Drug Carriers Production Processes for Innovative Human Applications)

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21 pages, 6914 KiB

Open AccessArticle

Quinine: Redesigned and Rerouted

by Chinazom Precious Agbo, Timothy Chukwuebuka Ugwuanyi, Osita Christopher Eze, Adaeze Linda Onugwu, Adaeze Chidiebere Echezona, Chinekwu Sherridan Nwagwu, Samuel Wisdom Uzondu, John Dike Ogbonna, Lydia Onyinyechi Ugorji, Petra Obioma Nnamani, Paul Achile Akpa, Joy Nneji Reginald-Opara, John Onyebuchi Ogbodo, Christopher McConville, Anthony Amaechi Attama, Mumuni Audu Momoh and Kenneth Chibuzor Ofokansi

Processes 2023, 11(6), 1811; https://doi.org/10.3390/pr11061811 - 14 Jun 2023

Cited by 3 | Viewed by 2248

Abstract

Quinine hydrochloride (QHCl) has remained a very relevant antimalarial drug 400 years after its effectiveness was discovered. Unlike other antimalarials, the development of resistance to quinine has been slow. Hence, this drug is to date still used for the treatment of severe and cerebral malaria, for malaria treatment in all trimesters of pregnancy, and in combination with doxycycline against multidrug-resistant malaria parasites. The decline in its administration over the years is mainly associated with poor tolerability due to its gastrointestinal (GIT) side effects such as cinchonism, complex dosing regimen and bitter taste, all of which result in poor compliance. Hence, our research was aimed at redesigning quinine using nanotechnology and investigating an alternative route for its administration for the treatment of malaria. QHCl nanosuspension (QHCl-NS) for intranasal administration was prepared using lipid matrices made up of solidified reverse micellar solutions (SRMS) comprising Phospholipon^® 90H and lipids (Softisan^® 154 or Compritol^®) in a 1:2 ratio, while Poloxamer^® 188 (P188) and Tween^® 80 (T80) were used as a stabilizer and a surfactant, respectively. The QHCl-NS formulated were in the nanosize range (68.60 ± 0.86 to 300.80 ± 10.11 nm), and highly stable during storage, though zeta potential was low (≤6.95 ± 0.416). QHCl-NS achieved above 80% in vitro drug release in 6 h. Ex vivo permeation studies revealed that formulating QHCl as NS resulted in a 5-fold and 56-fold increase in the flux and permeation coefficient, respectively, thereby enhancing permeation through pig nasal mucosa better than plain drug solutions. This implies that the rate of absorption as well as ease of drug permeation through porcine nasal mucosa was impressively enhanced by formulating QHCl as NS. Most importantly, reduction in parasitaemia in mice infected with Plasmodium berghei ANKA by QHCl-NS administered through the intranasal route (51.16%) was comparable to oral administration (52.12%). Therefore, redesigning QHCl as NS for intranasal administration has great potential to serve as a more tolerable option for the treatment of malaria in endemic areas. Full article

(This article belongs to the Special Issue Drug Carriers Production Processes for Innovative Human Applications)

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25 pages, 3942 KiB

Open AccessArticle

Formulation and Characterization of a Novel Palm-Oil-Based α-Mangostin Nano-Emulsion (PO-AMNE) as an Antimicrobial Endodontic Irrigant: An In Vitro Study

by Omer Sheriff Sultan, Haresh Kumar AL Kantilal, Khoo Suan Phaik, Hira Choudhury and Fabian Davamani

Processes 2023, 11(3), 798; https://doi.org/10.3390/pr11030798 - 7 Mar 2023

Cited by 2 | Viewed by 1889

Abstract

Aim: To formulate and characterize a palm-oil-in-water-based α-Mangostin nano-emulsion (PO-AMNE) endodontic irrigant, in order to evaluate its antibacterial efficacy against Enterococcus faecalis, Staphylococcus epidermidis, and Candida albicans biofilms, as well as its capacity to remove smear layer. Methods: The solubility of α-Mangostin in various oils was determined and selected, surfactants and co-surfactants were used for the nano-emulsion trial. PO-AMNE was prepared and optimized. The MIC was performed, and the antimicrobial efficacy was estimated against biofilms. The optimized 0.2% PO-AMNE irrigant antimicrobial efficacy in a tooth model was done using colony-forming units. The treated teeth were processed by scanning electron microscopic examination for debris and smear layer removal. An Alamar Blue assay was used to evaluate cell viability. The optimization of the PO-AMNE irrigant was performed using Box–Behnken statistical design. Results: The optimized 0.2% PO-AMNE irrigant was found to have a particle size of 340.9 nm with 0.246 PDI of the dispersed droplets, and a zeta potential (mV) of −27.2 ± 0.7 mV. The MIC values showed that 0.2% PO-AMNE (1.22 ± 0.02) were comparable to 2% CHX (1.33 ± 0.01), and 3.25% NaOCl (2.2 ± 0.09) had the least inhibition for E. faecalis. NaOCl (3.25%) showed the maximum inhibition of S. epidermidis (0.26 ± 0.05), whereas 0.2% PO-AMNE (1.25 ± 0.0) was comparable to 2% CHX (1.86 ± 0.07). For C. albicans, 2% CHX (8.12 ± 0.12) showed the least inhibition as compared to 0.2% PO-AMNE (1.23 ± 0.02) and 3.25% NaOCl (0.59 ± 0.02). The 0.2% PO-AMNE irrigant was then evaluated for its antimicrobial efficacy against the three biofilms, using colony-forming units. The 0.2% PO-AMNE was comparable to both 3.25% NaOCl and 2% CHX in inhibiting the growth of biofilms. The 0.2% PO-AMNE and 17% EDTA eliminated the smear layer with the lowest mean scores (p < 0.001). Finally, 0.2% PO-AMNE was shown to be biocompatible when compared to 17% EDTA, 3.25% NaOCl, and 2% CHX in immortalized oral keratinocyte cells. Conclusion: Overall, the formulated 0.2% PO-AMNE irrigant was an effective antimicrobial and biocompatible which could combat endodontic-infection-related polymicrobial biofilms. Full article

(This article belongs to the Special Issue Drug Carriers Production Processes for Innovative Human Applications)

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10 pages, 1376 KiB

Open AccessFeature PaperArticle

Discrete and Continuous Glucose Monitoring Systems: The Point of View of a Patient Affected by Type-1 Diabetes

by Paolo Trucillo

Processes 2022, 10(12), 2706; https://doi.org/10.3390/pr10122706 - 15 Dec 2022

Cited by 1 | Viewed by 1555

Abstract

This work represents the point of view of a diabetic patient with an indirect experience in this specific field of research. As a chemical engineer and researcher in drug carrier production, he has always approached type-1 diabetes (T1D) in a scientific manner. Therefore, this work represents a description of almost 20 years of this illness treatment using a multi-injection insulin system, compared with the experience acquired with a newly adopted micro-infusion system, allowing automatized insulin administration. The use of the continuous system reduced significantly the Hb1Ac average values, from 8.8% to 6.6%, in less than 2 years. Moreover, a full 24 h control guaranteed the almost total elimination of the hypoglycemia risk, thanks to the automated control system, that can stop insulin administration in order to prevent critical situations. It is also important to note that the point of view underlined in this work does not presume to be that of a doctor or of a researcher who works closely in the field of medicine or diabetology. However, the author wants to highlight that doctors could try to educate patients to a scientific approach to treat illnesses correctly. The author experienced the very common difficulties related to the use of insulin with multi-injection administration for many years; then, he was proposed to start treatment with the automated pump mechanism. In this work, the author provides comments on the physical and psychological advantages and disadvantages of both insulin release systems, in order to define their impact on a patient’s daily life. This work may also represent a vademecum for patients during the beginning of diabetes treatment, helped by the constant support and advice of a medical doctor. Full article

(This article belongs to the Special Issue Drug Carriers Production Processes for Innovative Human Applications)

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Review

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39 pages, 6200 KiB

Open AccessReview

Innovative and Patented Liposome-Based Drug Carriers

by Snežana Ilić-Stojanović, Suzana Cakić, Nada Nikolić and Slobodan Petrović

Processes 2024, 12(9), 1970; https://doi.org/10.3390/pr12091970 - 13 Sep 2024

Viewed by 988

Abstract

Liposome-based drug carriers are multipurpose colloidal drug delivery systems developed mainly for targeted therapy. Researchers have expanded their research on liposomes due to their unique characteristics (e.g., non-toxicity, biodegradability, biocompatibility, and non-immunogenicity). This review summarizes historical advances, from the first scientific papers and patents to the latest inventive solutions, in the field of liposome-based drug carriers and their production processes. Various bibliometric studies on the use of liposomes as drug carriers have been published; nevertheless, they focus on published scientific works rather than patent documents. Patent information is important for the pharmaceutical, nutraceutical, and cosmetic industries because technical knowledge in patent documentation is often not published in any other document. The research in this review was conducted using the Espacenet—European Patent Office database, with keywords and classification codes defined by the International Patent Classification. Innovative formulations, including the usage and administration route, are broadly researched to produce effective and safe drug delivery systems with negligible side effects. Global patenting trends in liposome drug carriers’ production process were also discussed, and this evaluation unifies up-to-date development in this field. Patent database reviews and analyses could help as inspiration for future investigations as well as for problem-solving resources. Full article

(This article belongs to the Special Issue Drug Carriers Production Processes for Innovative Human Applications)

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12 pages, 1520 KiB

Open AccessReview

Transdermal Patches Containing Opioids in the Treatment of Patients with Chronic Pain

by Iolanda De Marco

Processes 2023, 11(9), 2673; https://doi.org/10.3390/pr11092673 - 6 Sep 2023

Cited by 1 | Viewed by 3391

Abstract

Transdermal delivery is a non-invasive route, used as an alternative to the oral route, to administer drugs through the skin surface. One of the fields in which they are particularly used is that of pain therapy. In this treatment, transdermal patches, particularly those containing opioids, are used to complement or replace orally administered drugs. First-generation patches are constituted by reservoir systems, where the drug is dissolved in a solvent and gelled with a polymer. In contrast, the active principle is incorporated into the polymer adhesive in more recent matrix patches. In this review, the main papers related to the production and employment of transdermal patches containing the two most used opioids, i.e., fentanyl and buprenorphine, have been critically analyzed. From the analysis of the literature, it is possible to deduce that the type of drug and the amount of drug present in the patch must be chosen not according to the origin of the pain but to the age of the patient, the area where the patch is applied, and the frequency at which the patch is replaced. Full article

(This article belongs to the Special Issue Drug Carriers Production Processes for Innovative Human Applications)

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14 pages, 25414 KiB

Open AccessReview

Progress of Research on Antioxidants and Carriers for Skin Wound Repair

by Xiaoxuan Zhu, Wenlu Yuan, Zhuozheng Li, Yin Lin, Wenfang Li, Lei Ji, Dan Wang, Huafang Zhang and Yingshuai Wang

Processes 2023, 11(7), 2069; https://doi.org/10.3390/pr11072069 - 11 Jul 2023

Cited by 2 | Viewed by 2045

Abstract

The skin is the first protective barrier of the human body, and oxidative damage is one of the main mechanisms of skin injury. Effective antioxidant therapy plays an important role in skin healing. Therefore, exploring antioxidants and suitable drug delivery methods that can be used for skin injury repair is of great value in regulating skin repair and regeneration and promoting wound healing. Based on this, this paper presents a review of the progress of research on (1) antioxidants and (2) antioxidant carriers for skin repair in order to summarize the research results and provide reference for the subsequent development of new drug-carrier structures and new skin repair strategies. Full article

(This article belongs to the Special Issue Drug Carriers Production Processes for Innovative Human Applications)

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24 pages, 3950 KiB

Open AccessEditor’s ChoiceReview

Drug Carriers: A Review on the Most Used Mathematical Models for Drug Release

by Paolo Trucillo

Processes 2022, 10(6), 1094; https://doi.org/10.3390/pr10061094 - 31 May 2022

Cited by 62 | Viewed by 8224

Abstract

Carriers are protective transporters of drugs to target cells, facilitating therapy under each points of view, such as fast healing, reducing infective phenomena, and curing illnesses while avoiding side effects. Over the last 60 years, several scientists have studied drug carrier properties, trying to adapt them to the release environment. Drug/Carrier interaction phenomena have been deeply studied, and the release kinetics have been modeled according to the occurring phenomena involved in the system. It is not easy to define models’ advantages and disadvantages, since each of them may fit in a specific situation, considering material interactions, diffusion and erosion phenomena, and, no less important, the behavior of receiving medium. This work represents a critical review on main mathematical models concerning their dependency on physical, chemical, empirical, or semi-empirical variables. A quantitative representation of release profiles has been shown for the most representative models. A final critical comment on the applicability of these models has been presented at the end. A mathematical approach to this topic may help students and researchers approach the wide panorama of models that exist in literature and have been optimized over time. This models list could be of practical inspiration for the development of researchers’ own new models or for the application of proper modifications, with the introduction of new variable dependency. Full article

(This article belongs to the Special Issue Drug Carriers Production Processes for Innovative Human Applications)

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