Uncovering caregiver concerns: 5 key issues that still remain unresolved in administration of oral medicines for children in India

INTRODUCTION: Administration devices play a very crucial role in achieving a drug’s therapeutic effect. Children are often dosed with oral liquids, but dosing devices don’t have the accuracy needed, putting them at risk of inaccurate and suboptimal dosing. The availability and use of administration devices may vary throughout the world. Multiple surveys in UK, Europe and Japan have shown diverging practices by parents/caregivers. The aim of the present investigation was to conduct a larger Pan-India study through a series of workshops to understand the use and challenges of traditional devices and assess the need of innovative administration devices for liquid orals in India. METHODS: Administration devices play a very crucial role in achieving a drug’s therapeutic effect. Children are often dosed with oral liquids, but dosing devices don’t have the accuracy needed, putting them at risk of inaccurate and suboptimal dosing. The availability and use of administration devices may vary throughout the world. Multiple surveys in UK, Europe and Japan have shown diverging practices by parents/caregivers. The aim of the present investigation was to conduct a larger Pan-India study through a series of workshops to understand the use and challenges of traditional devices and assess the need of innovative administration devices for liquid orals in India. RESULTS: Across the four regions (4 metro cities) involved in the study, 271 caregivers agreed to participate in the workshops. 17.7 % administered solid dosage forms, 81.2 % administered liquid dosage form and the remaining 1.1 % opted for others. TRADITIONAL DEVICES: Caregivers reported the use of measuring cups (41.4 %) followed by household spoons (25.8 %), droppers (15.3 %), measuring spoons (2.6 %), and other dosing devices (5.5 %) for measuring oral liquids. 8.0 % did not use any of the dosing devices as they were administrating tablets and/or capsules. The ease-of-use score was the highest for the dropper (2.67 ± 0.68) and the lowest for the measuring spoon (2.00 ± 1.00). The reported challenges were categorised into five categories which also influences the preference of using administration devices. This includes device design, user experience and usability, sociocultural factors, such as beliefs, knowledge and education, regulatory, and market/distribution. INNOVATIVE DEVICES: The majority of the caregivers (86.7 %) were not aware of any of the innovative devices shown to them. 58.7 % were willing to use it if was recommended by the doctor, 1.5 % of caregivers would use it on pharmacists’ recommendation and 37.6 % parents would use it if came along with the medicine. The criteria considered by the parents for use of the innovative devices in the descending order were Doctor’s recommendation > Quality > Cost > Packed in medicine > Ease of use > Availability/accessibility. There were no differences observed among the low and high socioeconomic status of caregviers regarding the use of traditional devices, challenges faced and awareness about innovative devices. Overall, the study revealed heterogeneity in the SES for the use of administration devices in the four zones. The association of SES and opinion on the use of administration devices was demonstrated with no statistically significant interaction between caregiver SES and the use of administration devices. CONCLUSION: The workshop revealed the prevalence of traditional dosing devices like measuring cups, household spoons among the caregivers. It highlighted key issues with the use of appropriate administration devices for correct and accurate dosing in children that remain unresolved and prevalent in India. This study reflects on the needs of the target community; thus hope will help facilitate the development of locally sustainable solutions to improve the administration of medicines in children in India

The Role of Human MSC Derived Exosomes in the Treatment of Periodontal Diseases

Periodontal disease affects 47% of Americans over 30. Characterized by microbial dysbiosis and unregulated inflammation, severe periodontitis causes degradation of bone and soft tissue around teeth. Current treatments have limited regenerative outcomes and frequent reinfection by harmful bacteria. Human mesenchymal stem cells (hMSCs) have been shown to promote wound healing and tissue regeneration. Many therapeutic benefits of hMSCs are due to their secretome products, like exosomes. Our long-term goal is to develop periodontal therapies with hMSC exosomes. The objectives of this study were to determine the effect of hMSC-derived exosomes on cellular activity of hMSCs and investigate whether hMSC exosome treatment reduces pro-inflammatory cytokine production in LPS-activated RAW264.7 cells. The specific aims of this study were: 1) Determine the characteristics of hMSC-derived exosomes, 2) Determine the biological effect of exosomes on cellular activity of hMSCs, 3) Determine whether exosomes treatment can inhibit cytokine production in activated RAW264.7 cells, and 4) Determine the role of exosomal miRNA in pro-inflammatory cytokine production of RAW264.7 cells. To investigate, exosomes were first harvested from hMSCs culture media through ultracentrifugation. Exosomes were then observed under a transmission electron microscope (TEM) and assessed for surface markers using Western Blot. A transwell migration assay was used to evaluate the chemotactic effect of exosomes. To study the effect of exosomes on stem cell proliferation, exosomes were administered to hMSCs. The immunogenicity of MSC exosome was also evaluated. After 72 hours, cells were lysed and DNA was measured. To study anti-inflammatory effects of exosomes, LPS stimulated RAW264.7 cells were treated with exosomes. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) levels of supernatant were measured by ELISA. To study exosomal miRNA, exosomal miRNAs were overexpressed in RAW264.7 cells and these cells were stimulated with LPS. IL-6 and TNFα were measured by ELISA. TEM images showed that exosomes are nano-sized vesicles (~100 nm). Western blot images showed that CD63 and CD81 are enriched in exosomes compared to total cell lysates. Exosome treatment increased cell proliferation and migration in hMSCs. At the doses that are chemotactic and mitogenic, MSC exosomes had minimal effect on the inflammatory cytokine IL-6 production. Treatment with exosomes significantly decreased IL-6 and TNFα production in RAW264.7 cells activated by LPS. Transfecting RAW264.7 cells with exosomal miR-760 significantly decreased IL-6 production, but had minimal effect on TNFα. Our results indicate that exosomes have a pleiotropic activity, which includes stimulating stem cell migration and proliferation, and mitigating the inflammatory response. Therefore, hMSC exosome delivery is promising for the treatment of periodontal diseases

Intranasal delivery: An approach to bypass the blood brain barrier

The blood brain barrier (BBB) represents one of the strictest barriers of in vivo therapeutic drug delivery. The barrier is defined by restricted exchange of hydrophilic compounds, small proteins and charged molecules between the plasma and central nervous system (CNS). For decades, the BBB has prevented the use of many therapeutic agents for treating Alzheimer's disease, stroke, brain tumor, head injury, spinal cord injury, depression, anxiety and other CNS disorders. Different attempts were made to deliver the drug across the BBB such as modification of therapeutic agents, altering the barrier integrity, carrier-mediated transport, invasive techniques, etc. However, opening the barrier by such means allows entry of toxins and undesirable molecules to the CNS, resulting in potentially significant damage. An attempt to overcome the barrier in vivo has focused on bypassing the BBB by using a novel, practical, simple and non-invasive approach i.e. intranasal delivery. This method works because of the unique connection which the olfactory and trigeminal nerves (involved in sensing odors and chemicals) provide between the brain and external environments. The olfactory epithelium acting as a gateway for substances entering the CNS and peripheral circulation is well known. Also, it is common knowledge that viral infections such as common cold, smallpox, measles, and chicken pox take place through the nasopharynx. The neural connections between the nasal mucosa and the brain provide a unique pathway for the non-invasive delivery of therapeutic agents to the CNS. This pathway also allows drugs which do not cross the BBB to enter the CNS and it eliminates the need for systemic delivery and thereby reducing unwanted systemic side effects. Intranasal delivery does not require any modification of therapeutic agents and does not require that drugs be coupled with any carrier. A wide variety of therapeutic agents, including both small molecules and macromolecules can be rapidly delivered to the CNS using this method. The present review discusses the various applications, advantages and limitations of this novel approach

Cellulose nanofiber aerogel as a promising biomaterial for customized oral drug delivery

Jyoti Bhandari,1 Harshita Mishra,1 Pawan Kumar Mishra,2 Rupert Wimmer,2,3 Farhan J Ahmad,1 Sushama Talegaonkar1 1Department of Pharmaceutics, Jamia Hamdard, New Delhi, India; 2Department of Wood Science, Mendel University in Brno, Brno, Czech Republic; 3Institute for Natural Materials Technology, Department of Agrobiotechnology, IFA-Tulln, University of Natural Resources and Life Sciences, Vienna, Austria Abstract: Cellulose nanofiber (CNF) aerogels with favorable floatability and mucoadhesive properties prepared by the freeze-drying method have been introduced as new possible carriers for oral controlled drug delivery system. Bendamustine hydrochloride is considered as the model drug. Drug loading was carried out by the physical adsorption method, and optimization of drug-loaded formulation was done using central composite design. A very lightweight-aerogel-with-matrix system was produced with drug loading of 18.98%±1.57%. The produced aerogel was characterized for morphology, tensile strength, swelling tendency in media with different pH values, floating behavior, mucoadhesive detachment force and drug release profiles under different pH conditions. The results showed that the type of matrix was porous and woven with excellent mechanical properties. The drug release was assessed by dialysis, which was fitted with suitable mathematical models. Approximately 69.205%±2.5% of the drug was released in 24 hours in medium of pH 1.2, whereas ~78%±2.28% of drug was released in medium of pH 7.4, with floating behavior for ~7.5 hours. The results of in vivo study showed a 3.25-fold increase in bioavailability. Thus, we concluded that CNF aerogels offer a great possibility for a gastroretentive drug delivery system with improved bioavailability. Keywords: cellulose nanofiber, aerogel, controlled release, gastroretentive, floating behavior, swelling behavior, mucoadhesion, bioavailabilit