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Polymers Aug 2023Micro- and nanotechnologies have been intensively studied in recent years as novel platforms for targeting and controlling the delivery of various pharmaceutical... (Review)
Review
Micro- and nanotechnologies have been intensively studied in recent years as novel platforms for targeting and controlling the delivery of various pharmaceutical substances. Microparticulate drug delivery systems for oral, parenteral, or topical administration are multiple unit formulations, considered as powerful therapeutic tools for the treatment of various diseases, providing sustained drug release, enhanced drug stability, and precise dosing and directing the active substance to specific sites in the organism. The properties of these pharmaceutical formulations are highly dependent on the characteristics of the polymers used as drug carriers for their preparation. Starch and cellulose are among the most preferred biomaterials for biomedical applications due to their biocompatibility, biodegradability, and lack of toxicity. These polysaccharides and their derivatives, like dextrins (maltodextrin, cyclodextrins), ethylcellulose, methylcellulose, hydroxypropyl methylcellulose, carboxy methylcellulose, etc., have been widely used in pharmaceutical technology as excipients for the preparation of solid, semi-solid, and liquid dosage forms. Due to their accessibility and relatively easy particle-forming properties, starch and cellulose are promising materials for designing drug-loaded microparticles for various therapeutic applications. This study aims to summarize some of the basic characteristics of starch and cellulose derivatives related to their potential utilization as microparticulate drug carriers in the pharmaceutical field.
PubMed: 37688241
DOI: 10.3390/polym15173615 -
Journal of Investigational Allergology... Dec 2023Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are... (Review)
Review
Ocular allergy covers a series of immune-allergic inflammatory diseases of the ocular surface, with different degrees of involvement and severity. These pathologies are caused by a variety of IgE- and non-IgE-mediated immune mechanisms and may involve all parts of the external eye, including the conjunctiva, cornea, eyelids, tear film, and commensal flora. The most frequent is allergic conjunctivitis, a condition with different clinical forms that are classified according to the degree of involvement and the presence or absence of proliferative changes in the palpebral conjunctiva, associated atopic dermatitis, and mechanical stimuli by foreign bodies, including contact lenses. Treatment guidelines for allergic conjunctivitis propose a stepwise approach that includes medications for both ophthalmic and oral administration depending on symptom severity, allergic comorbidities, and degree of control. In the case of antihistamines, eye drops are the most prescribed ophthalmic formulations. To avoid disrupting the delicate balance of the ocular surface, topical ophthalmic medications must be well tolerated. The primary aim of this article is to review the physicochemical characteristics and other features of excipients (preservative agents, buffers, pH adjusters, viscosity enhancers, wetting agents or cosolvents, antioxidants, tonicity adjusters, and osmo-protectants) and active compounds (ocular antihistamines) that must be considered when developing formulations for ophthalmic administration of antihistamines. We also provide a brief overview of antihistamine eye drops that could be of interest to professionals treating ocular allergy and encourage the use of preservative-free formulations when possible.
Topics: Humans; Conjunctivitis, Allergic; Histamine Antagonists; Histamine H1 Antagonists; Ophthalmic Solutions
PubMed: 38095492
DOI: 10.18176/jiaci.0963 -
Pharmaceutics Jul 2023Risk control for nitrosamine impurities in drug products is currently a major challenge in the industry. Nitrosamines can form during drug product manufacturing and...
Risk control for nitrosamine impurities in drug products is currently a major challenge in the industry. Nitrosamines can form during drug product manufacturing and storage through the reaction of nitrites with amine-containing APIs or impurities. The level of nitrites in excipients and the rate of reaction often control the build-up of nitrosamine. Although the variability in nitrite levels across excipient types and suppliers is well recognized, the impact of excipient selection on the level of nitrosamine formed has not been systematically studied. This gap of knowledge is addressed in the current work. We present theoretical case studies of formulations where microcrystalline cellulose (MCC), or lactose supplier, or superdisintegrant type are changed in pursuit of lower levels of nitrite. The impact of the average, maximum, and minimum levels of nitrites in each excipient on nitrosamine formation in the dosage form is calculated. The input data for this calculation are the formulation composition, nitrosamine molecular weight (MW), percentage of conversion, and nitrite levels per excipient. The percentage of conversion (based on the formulation and manufacturing variables) and nitrite levels were taken from the recent literature. We show that changing the supplier of a single excipient, or of the three most critical excipients, can reduce nitrosamine formation by up to -59% and -89%, respectively. We also show that high-risk formulations, e.g., high MW nitrosamines, high dosage weights, and high percentages of conversion (e.g., wet granulation), can often be de-risked below regulatory acceptable daily intake via careful excipient selection. Finally, we provide an open-access tool that enables users to calculate the theoretical formation of nitrosamines in their specific formulations. This calculation template can be used for (i) the preliminary screening of the risk of nitrosamine formation in drug products and (ii) the preliminary assessment of the impact of excipient selection for risk mitigation.
PubMed: 37631229
DOI: 10.3390/pharmaceutics15082015 -
Molecules (Basel, Switzerland) Nov 2023Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but...
Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but also facilitates the absorption of multiple drugs. Our previous study found that the long-term application of PEG400 as an adjuvant in traditional Chinese medicine preparations resulted in wasting and weight loss in animals, which aroused our concern. In this study, 16S rRNA high-throughput sequencing technology was used to analyze the diversity of gut microbiota, and LC-MS/MS Q-Exactive Orbtriap metabolomics technology was used to analyze the effect of PEG400 on the metabolome of healthy mice, combined with intestinal pathological analysis, aiming to investigate the effects of PEG400 on healthy mice. These results showed that PEG400 significantly altered the structure of gut microbiota, reduced the richness and diversity of intestinal flora, greatly increased the abundance of (), increased the proportion of Bacteroidetes to Firmicutes, and reduced the abundance of many beneficial bacteria. Moreover, PEG400 changed the characteristics of fecal metabolome in mice and induced disorders in lipid and energy metabolism, thus leading to diarrhea, weight loss, and intestinal inflammation in mice. Collectively, these findings provide new evidence for the potential effect of PEG400 ingestion on a healthy host.
Topics: Mice; Animals; Gastrointestinal Microbiome; Excipients; RNA, Ribosomal, 16S; Chromatography, Liquid; Tandem Mass Spectrometry; Metabolome; Weight Loss
PubMed: 38005284
DOI: 10.3390/molecules28227562 -
Pharmaceutics Oct 2023Bacteriophages (phages) are nano-sized viruses characterized by their inherent ability to live off bacteria. They utilize diverse mechanisms to absorb and gain entry... (Review)
Review
Bacteriophages (phages) are nano-sized viruses characterized by their inherent ability to live off bacteria. They utilize diverse mechanisms to absorb and gain entry into the bacterial cell wall via the release of viral genetic material, which uses the replication mechanisms of the host bacteria to produce and release daughter progeny virions that attack the surrounding host cells. They possess specific characteristics, including specificity for particular or closely related bacterial species. They have many applications, including as potential alternatives to antibiotics against multi-resistant bacterial pathogens and as control agents in bacteria-contaminated environments. They are ubiquitously abundant in nature and have diverse biota, including in the gut. Gut microbiota describes the community and interactions of microorganisms within the intestine. As with bacteria, parasitic bacteriophages constantly interact with the host bacterial cells within the gut system and have obvious implications for human health. However, it is imperative to understand these interactions as they open up possible applicable techniques to control gut-implicated bacterial diseases. Thus, this review aims to explore the interactions of bacteriophages with bacterial communities in the gut and their current and potential impacts on human health.
PubMed: 37896176
DOI: 10.3390/pharmaceutics15102416 -
Scientific Reports Sep 2023Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ...
Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic-ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 10 cells/body) or Hank's balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel.
Topics: Humans; Animals; Rats; Animals, Newborn; Alprostadil; Hypoxia-Ischemia, Brain; Hypoxia; Excipients; Brain Injuries
PubMed: 37696826
DOI: 10.1038/s41598-023-41026-3 -
European Journal of Pharmaceutical... Nov 2023The oral delivery of biologics such as therapeutic proteins, peptides and oligonucleotides for the treatment of colon related diseases has been the focus of increasing... (Review)
Review
The oral delivery of biologics such as therapeutic proteins, peptides and oligonucleotides for the treatment of colon related diseases has been the focus of increasing attention over the last years. However, the major disadvantage of these macromolecules is their degradation propensity in liquid state which can lead to the undesirable and complete loss of function. Therefore, to increase the stability of the biologic and reduce their degradation propensity, formulation techniques such as solidification can be performed to obtain a stable solid dosage form for oral administration. Due to their fragility, stress exerted on the biologic during solidification has to be reduced with the incorporation of stabilizing excipients into the formulation. This review focuses on the state-of-the-art solidification techniques required to obtain a solid dosage form for the oral delivery of biologics to the colon and the use of suitable excipients for adequate stabilization upon solidification. The solidifying processes discussed within this review are spray drying, freeze drying, bead coating and also other techniques such as spray freeze drying, electro spraying, vacuum- and supercritical fluid drying. Further, the colon as site of absorption in both healthy and diseased state is critically reviewed and possible oral delivery systems for biologics are discussed.
Topics: Excipients; Desiccation; Freeze Drying; Biological Products; Colon
PubMed: 37429482
DOI: 10.1016/j.ejps.2023.106523 -
International Journal of Nanomedicine 2023Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results in the treatment of hematological tumors....
INTRODUCTION
Chimeric antigen receptor (CAR) cell therapy represents a hallmark in cancer immunotherapy, with significant clinical results in the treatment of hematological tumors. However, current approved methods to engineer T cells to express CAR use viral vectors, which are integrative and have been associated with severe adverse effects due to constitutive expression of CAR. In this context, non-viral vectors such as ionizable lipid nanoparticles (LNPs) arise as an alternative to engineer CAR T cells with transient expression of CAR.
METHODS
Here, we formulated a mini-library of LNPs to deliver pDNA to T cells by varying the molar ratios of excipient lipids in each formulation. LNPs were characterized and screened in vitro using a T cell line (Jurkat). The optimized formulation was used ex vivo to engineer T cells derived from human peripheral blood mononuclear cells (PBMCs) for the expression of an anti-CD19 CAR (CAR-CD19BBz). The effectiveness of these CAR T cells was assessed in vitro against Raji (CD19) cells.
RESULTS
LNPs formulated with different molar ratios of excipient lipids efficiently delivered pDNA to Jurkat cells with low cytotoxicity compared to conventional transfection methods, such as electroporation and lipofectamine. We show that CAR-CD19BBz expression in T cells was transient after transfection with LNPs. Jurkat cells transfected with our top-performing LNPs underwent activation when exposed to CD19 target cells. Using our top-performing LNP-9-CAR, we were able to engineer human primary T cells to express CAR-CD19BBz, which elicited significant specific killing of CD19 target cells in vitro.
CONCLUSION
Collectively, our results show that LNP-mediated delivery of pDNA is a suitable method to engineer human T cells to express CAR, which holds promise for improving the production methods and broader application of this therapy in the future.
Topics: Humans; Excipients; Leukocytes, Mononuclear; Plasmids; Nanoparticles; DNA; Lipids
PubMed: 37873551
DOI: 10.2147/IJN.S424723 -
ACS Omega Dec 2023Pectin is a structural polysaccharide present in plants that primarily consists of galacturonic acid units. This Review discusses the chemistry of pectin, including its... (Review)
Review
Pectin is a structural polysaccharide present in plants that primarily consists of galacturonic acid units. This Review discusses the chemistry of pectin, including its composition and molecular weight. Pectin is conventionally extracted from agricultural waste (fruit and vegetable peels) using an acidic or basic aqueous medium at high temperatures. These processes are time- and energy-consuming and also result in severe environmental problems due to the production of acidic effluents and equipment corrosion. As pectin usage is increasing in food industries for developing different products and it is also used as an excipient in pharmaceutical products, better extraction procedures are required to maximize the yield and purity. The Review encompasses various alternate green approaches for the extraction of pectin, including traditional acid extraction and various emerging technologies such as deep eutectic solvent-based extraction, enzyme-assisted extraction, subcritical fluid extraction, ultrasound-assisted extraction, and microwave-based extraction, and evaluates the yield and physicochemical characteristics of the extracted pectin. This work aims to provide a platform for attracting more thorough research focused on the engineering of novel and more efficient green methods for the extraction of pectin and its utilization for various biotechnological purposes.
PubMed: 38107881
DOI: 10.1021/acsomega.3c04010 -
ACS Omega Oct 2023Active pharmaceutical ingredients (APIs) and excipients are main drug constituents that ought to be identified qualitatively and quantitatively. Raman spectroscopy is...
Active pharmaceutical ingredients (APIs) and excipients are main drug constituents that ought to be identified qualitatively and quantitatively. Raman spectroscopy is aimed to be an efficient technique for pharmaceutical analysis in solid dosage forms. This technique can successfully be used in terms of qualitative and quantitative analysis of pharmaceutical drugs, their APIs, and excipients. In the proposed research, Raman spectroscopy has been employed to quantify Azithromycin based on its distinctive Raman spectral features by using commercially prepared formulations with altered API concentrations and excipients as well. Along with Raman spectroscopy, principal component analysis and partial least squares regression (PLSR), two multivariate data analysis techniques have been used for the identification and quantification of the API. For PLSR, goodness of fit of the model () was found to be 0.99, whereas root mean square error of calibration was 0.46 and root mean square error of prediction was 2.42, which represent the performance of the model. This study highlights the efficiency of Raman spectroscopy in the field of pharmaceutics by preparing pharmaceutical formulations of any drug to quantify their API and excipients to compensate for the commercially prepared concentrations.
PubMed: 37810726
DOI: 10.1021/acsomega.3c05245